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Gomes E, Araújo D, Nogueira T, Oliveira R, Silva S, Oliveira LVN, Azevedo NF, Almeida C, Castro J. Advances in whole genome sequencing for foodborne pathogens: implications for clinical infectious disease surveillance and public health. Front Cell Infect Microbiol 2025; 15:1593219. [PMID: 40357405 PMCID: PMC12066639 DOI: 10.3389/fcimb.2025.1593219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Accepted: 04/04/2025] [Indexed: 05/15/2025] Open
Abstract
Foodborne outbreaks affecting millions of people worldwide are a significant and growing global health threat, exacerbated by the emergence of new and increasingly virulent foodborne pathogens. Traditional methods of detecting these outbreaks, including culture-based techniques, serotyping and molecular methods such as real-time PCR, are still widely used. However, these approaches often lack the precision and resolution required to definitively trace the source of an outbreak and distinguish between closely related strains of pathogens. Whole genome sequencing (WGS) has emerged as a revolutionary tool in outbreak investigations, providing high-resolution, comprehensive genetic data that allows accurate species identification and strain differentiation. WGS also facilitates the detection of virulence and antimicrobial resistance (AMR) genes, providing critical insight into the potential pathogenicity, treatment/control options and risks of spreading foodborne pathogens. This capability enhances outbreak surveillance, source tracing and risk assessment, making WGS an increasingly integrated component of public health surveillance systems. Despite its advantages, the widespread implementation of WGS faces several pressing challenges, including high sequencing costs, the need for specialized bioinformatics expertise, limited computational infrastructure in resource-constrained settings, and the standardization of data-sharing frameworks across regulatory and public health agencies. Addressing these barriers is crucial to maximizing the impact of WGS on foodborne disease surveillance. Even so, WGS is emerging as a vital tool in food safety and public health, and its potential to become the gold standard in outbreak detection has been recognized by public health authorities in the USA, the European Union, Australia and China, for example. This review highlights the role of WGS in foodborne outbreak investigations, its implementation challenges, and its impact on public health surveillance.
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Affiliation(s)
- Emílio Gomes
- INIAV—National Institute for Agrarian and Veterinary Research, Vila do Conde, Portugal
- LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
- ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Porto, Portugal
| | - Daniela Araújo
- INIAV—National Institute for Agrarian and Veterinary Research, Vila do Conde, Portugal
- CEB - Centre of Biological Engineering, University of Minho, Braga, Portugal
| | - Teresa Nogueira
- INIAV—National Institute for Agrarian and Veterinary Research, Vila do Conde, Portugal
- CE3C—Centre for Ecology, Evolution and Environmental Changes & CHANGE, Global Change and Sustainability Institute, Faculty of Sciences, University of Lisbon, Lisboa, Portugal
| | - Ricardo Oliveira
- INIAV—National Institute for Agrarian and Veterinary Research, Vila do Conde, Portugal
- LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
- ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Porto, Portugal
| | - Sónia Silva
- CEB - Centre of Biological Engineering, University of Minho, Braga, Portugal
- LABBELS – Associate Laboratory, Braga, Guimarães, Portugal
| | - Lorena V. N. Oliveira
- Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, United States
| | - Nuno F. Azevedo
- LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
- ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Porto, Portugal
| | - Carina Almeida
- INIAV—National Institute for Agrarian and Veterinary Research, Vila do Conde, Portugal
- LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
- ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Porto, Portugal
- CEB - Centre of Biological Engineering, University of Minho, Braga, Portugal
| | - Joana Castro
- INIAV—National Institute for Agrarian and Veterinary Research, Vila do Conde, Portugal
- CEB - Centre of Biological Engineering, University of Minho, Braga, Portugal
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Chu AT, Sze SY, Tse DM, Lai CW, Ng CS, Yu CW, Chung PH, Pang FC, Chung BH, Lo SV, Quan J. Experiences of participants with undiagnosed diseases and hereditary cancers during the initial phase of the Hong Kong genome project: a mixed-methods study. Hum Genomics 2025; 19:36. [PMID: 40188098 PMCID: PMC11972539 DOI: 10.1186/s40246-025-00746-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Accepted: 03/22/2025] [Indexed: 04/07/2025] Open
Abstract
BACKGROUND The Hong Kong Genome Project (HKGP) is the first population-wide whole genome sequencing (WGS) programme in Hong Kong and aimed to integrate genomic medicine into the healthcare system. Implementing genetic counselling is essential to help participants understand the genetic basis of diseases and guide informed decision making. We assessed participant experiences during the initial HKGP pilot phase that enrolled patients with undiagnosed diseases and hereditary cancers. METHODS Participants were recruited from three partnering centres at public hospitals during June-September 2023. Participant surveys covered four domains: (1) overall satisfaction, (2) informed consent process, (3) genetic counselling, and (4) attitude towards HKGP. Associations with demographic and socioeconomic characteristics were assessed with multivariable logistic regression. Qualitative feedback was collected in focus group interviews. RESULTS Among 422 eligible participants, 341 completed the survey (80.8% response) and five focus group interviews were held (21 participants). We found 89.8% [95% CI: 86.1-92.7] were satisfied with their HKGP experience. Almost all felt that HKGP participation could benefit others (86.8% [95% CI: 82.7-90.0]) and advance genomic research in Hong Kong (88.9% [95% CI: 85.0-91.9]). The survey item with the lowest agreement among respondents was feeling that HKGP participation could improve their/child's medical treatment (73.5% [95% CI: 68.5-78.0]). Those with secondary and tertiary education were less likely to agree genetic counselling was helpful (Odds Ratio [OR]: 0.02 [95% CI: 0.001-0.41]; 0.02 [0.001-0.51]), or the appropriate length of time (OR: 0.12 [95% CI: 0.014-0.81]; 0.11 [0.01-0.91]). Focus group participants cited helping scientific advances and shortening the diagnostic odyssey of future patients as key reasons for participation. Participants hoped for a shorter reporting time of WGS results, additional medical follow-up, and allowing referral of relatives. CONCLUSIONS Participants were overall highly satisfied with the HKGP and genetic counselling experience. Satisfaction levels were comparable to overseas genomic programmes and locally provided healthcare services. Participants' major concerns on WGS reporting time could be addressed by strengthening the informed consent process to ensure their expectations align with project implementation. Emphasizing the long-term value of genomic research and its potential for personalized treatments may increase participant engagement.
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Affiliation(s)
- Annie Tw Chu
- Hong Kong Genome Institute, Hong Kong SAR, China
| | - Samuel Yc Sze
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | | | - Cheryl Wy Lai
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Carmen S Ng
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Coco Ws Yu
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Pui-Hong Chung
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | | | - Brian Hy Chung
- Hong Kong Genome Institute, Hong Kong SAR, China.
- Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
| | - Su-Vui Lo
- Hong Kong Genome Institute, Hong Kong SAR, China.
| | - Jianchao Quan
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
- HKU Business School, The University of Hong Kong SAR, Hong Kong SAR, China.
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Thomson A, Rehn J, Yeung D, Breen J, White D. Deciphering IGH rearrangement complexity and detection strategies in acute lymphoblastic leukaemia. NPJ Precis Oncol 2025; 9:99. [PMID: 40185891 PMCID: PMC11971345 DOI: 10.1038/s41698-025-00887-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 03/19/2025] [Indexed: 04/07/2025] Open
Abstract
Acute lymphoblastic leukaemia is a highly heterogeneous malignancy characterised by various genomic alterations that influence disease progression and therapeutic outcomes. Gene fusions involving the immunoglobulin heavy chain gene represent a complex and diverse category. These fusions often result in enhancer hijacking, upregulation of partner proto-oncogenes and contribute to leukemogenesis. This review highlights the mechanisms underlying IGH gene fusions, the critical role they play in ALL pathogenesis, and current detection technologies.
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Affiliation(s)
- Ashlee Thomson
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia.
- Blood Cancer Program, Precision Cancer Medicine Theme, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia.
| | - Jacqueline Rehn
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia
- Blood Cancer Program, Precision Cancer Medicine Theme, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia
| | - David Yeung
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia
- Blood Cancer Program, Precision Cancer Medicine Theme, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia
- Haematology Department, Royal Adelaide Hospital and SA Pathology, Adelaide, SA, 5000, Australia
| | - James Breen
- Black Ochre Data Labs, Indigenous Genomics, The Kids Research Institute Australia, Adelaide, SA, 5000, Australia
- James Curtin School of Medical Research, Australian National University, Canberra, ACT, 2601, Australia
| | - Deborah White
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia.
- Blood Cancer Program, Precision Cancer Medicine Theme, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia.
- Australian and New Zealand Children's Oncology Group (ANZCHOG), Clayton, VIC, 3168, Australia.
- Australian Genomics Health Alliance (AGHA), The Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia.
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Zandstra D, Ralf A, Ozgur Z, van IJcken WFJ, Ghanbari M, Kayser M. Unprecedented male relative differentiation with Y-SNVs from whole genome sequencing. Forensic Sci Int Genet 2025; 78:103265. [PMID: 40112633 DOI: 10.1016/j.fsigen.2025.103265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 02/24/2025] [Accepted: 03/05/2025] [Indexed: 03/22/2025]
Abstract
The principal limitation of forensic Y-STR analysis, which identifies a male lineage rather than an individual man, is being addressed by the discovery and application of rapidly mutating Y-STRs (RM Y-STRs). Due to their higher mutation rates compared to standard Y-STRs used in forensics, RM Y-STRs significantly enhance the ability to differentiate between male relatives. However, some male relatives - particularly closely related ones - remain indistinguishable. Given the design and execution of the two previous RM Y-STR searches that discovered the 26 currently known RM Y-STRs, it is unlikely that future searches will largely increase the number of RM Y-STRs. To address the ongoing forensic challenge of differentiating between male relatives using Y chromosome analysis, this study explorers an alternative approach: Y-chromosomal singe nucleotide variants (Y-SNVs) obtained via whole genome sequencing (WGS). To assess the feasibility of the WGS technology in differentiating closely and distantly related males, we sequenced DNA samples of 24 male individuals belonging to three deep-rooted pedigrees, covering 12 father-son pairs and 72 pairs of distant male relatives separated by 8-15 meioses. Among the 76 meioses analyzed in total, 90 male relative-differentiating Y-SNVs were identified across the approximately 25 Mbp Y chromosome sequence generated per sample. A total of 141 male relative-differentiating Y chromosome mutations were observed when also considering Y-STRs from Yfiler Plus, RMplex, and WGS analyses. Of the 12 father-son pairs, six (50 %) were differentiated by one or more Y-SNVs, and 9 (75 %) with WGS and CE methods combined. All of the 72 pairs of distant male relatives were distinguished both through Y-SNVs and RM Y-STRs. Overall, when compared to RMplex, WGS yielded a 1.7-fold increase in the number of observed mutations in father-son pairs and a 4-fold increase in distantly related males. Our proof-of-principle study demonstrates (i) the feasibility and high value of Y-SNV markers and WGS technology in differentiating both close and distant male relatives; (ii) the superior performance of Y-SNVs from WGS relative to the previously used RM Y-STR markers and RMplex method; and (iii) the enhanced male relative differentiation achieved by combining both marker types and methods. We envision WGS as the method of choice for maximizing male relative differentiation based on Y chromosome information in high-profile criminal cases with male suspects where no autosomal STR profiles are available and where standard Y-STR and RM Y-STR analyses fail to distinguish the suspect from his male paternal relatives.
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Affiliation(s)
- Dion Zandstra
- Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Arwin Ralf
- Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Zeliha Ozgur
- Genomics Core Facility, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Wilfred F J van IJcken
- Genomics Core Facility, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Mohsen Ghanbari
- Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Manfred Kayser
- Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
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Carroll AC, Mortimer L, Ghosh H, Reuter S, Grundmann H, Brinda K, Hanage WP, Li A, Paterson A, Purssell A, Rooney A, Yee NR, Coburn B, Able-Thomas S, Antonio M, McGeer A, MacFadden DR. Rapid inference of antibiotic susceptibility phenotype of uropathogens using metagenomic sequencing with neighbor typing. Microbiol Spectr 2025; 13:e0136624. [PMID: 39611823 PMCID: PMC11705937 DOI: 10.1128/spectrum.01366-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 11/10/2024] [Indexed: 11/30/2024] Open
Abstract
Timely diagnostic tools are needed to improve antibiotic treatment. Pairing metagenomic sequencing with genomic neighbor typing algorithms may support rapid clinically actionable results. We created resistance-associated sequence elements (RASE) databases for Escherichia coli and Klebsiella spp. and used them to predict antibiotic susceptibility in directly sequenced (Oxford Nanopore) urine specimens from critically ill patients. RASE analysis was performed on pathogen-specific reads from metagenomic sequencing. We evaluated the ability to predict (i) multi-locus sequence type (MLST) and (ii) susceptibility profiles. We used neighbor typing to predict MLST and susceptibility phenotype of E. coli (64/80) and Klebsiella spp. (16/80) from urine samples. When optimized by lineage score, MLST predictions were concordant for 73% of samples. Similarly, a RASE-susceptible prediction for a given isolate was associated with a specificity and a positive likelihood ratio (LR+) for susceptibility of 0.65 (95% CI, 0.54-0.76) and 2.26 (95% CI, 1.75-2.92), respectively, with an increase in the probability of susceptibility of 10%. A RASE-non-susceptible prediction was associated with a sensitivity and a negative likelihood ratio (LR-) for susceptibility of 0.79 (95% CI, 0.74-0.84) and 0.32 (95% CI, 0.24-0.43) respectively, with a decrease in the probability of susceptibility of 20%. Numerous antibiotic classes could reasonably be reconsidered empiric therapy by shifting empiric probabilities of susceptibility across relevant treatment thresholds. Moreover, these predictions can be available within 6 h. Metagenomic sequencing of urine specimens with neighbor typing provides rapid and informative predictions of lineage and antibiotic susceptibility with the potential to impact clinical decision-making. IMPORTANCE Urinary tract infections (UTIs) are a common diagnosis in hospitals and are often treated empirically with broad-spectrum antibiotics. These broad-spectrum agents can select for resistance in these bacteria and co-colonizing organisms. The use of narrow-spectrum agents is desirable as an antibiotic stewardship measure; however, it is counterbalanced by the need for adequate therapy. Identification of causative organisms and their antibiotic susceptibility can help direct treatment; however, conventional testing requires days to produce actionable results. Methods to quickly and accurately predict susceptibility phenotypes for pathogens causing UTI could thus improve both patient outcomes and antibiotic stewardship. Here, expanding on previous work showing accurate prediction for certain Gram-positive pathogens, we demonstrate how the use of RASE from metagenomic sequencing can provide informative and rapid phenotype prediction results for common Gram-negative pathogens in UTI, highlighting the future potential of this method to be used in clinical settings to guide empiric antibiotic selection.
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Affiliation(s)
| | - Leanne Mortimer
- The Eastern Ontario Regional Laboratory, Ottawa, Ontario, Canada
| | | | | | | | | | - William P. Hanage
- Harvard T.H Chan School of Public Health, Harvard University, Cambridge, Massachusetts, USA
| | - Angel Li
- Sinai Health, Toronto, Ontario, Canada
| | | | | | | | - Noelle R. Yee
- The University of Toronto, Toronto, Ontario, Canada
- University Health Network, Toronto, Ontario, Canada
| | - Bryan Coburn
- The University of Toronto, Toronto, Ontario, Canada
- University Health Network, Toronto, Ontario, Canada
| | - Shola Able-Thomas
- MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia
| | - Martin Antonio
- MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia
- Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
- Centre for Epidemic Preparedness and Response, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Allison McGeer
- Sinai Health, Toronto, Ontario, Canada
- The University of Toronto, Toronto, Ontario, Canada
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Ahmed F, Zhong J. Advances in DNA/RNA Sequencing and Their Applications in Acute Myeloid Leukemia (AML). Int J Mol Sci 2024; 26:71. [PMID: 39795930 PMCID: PMC11720148 DOI: 10.3390/ijms26010071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 11/24/2024] [Accepted: 12/19/2024] [Indexed: 01/13/2025] Open
Abstract
Acute myeloid leukemia (AML) is an aggressive malignancy that poses significant challenges due to high rates of relapse and resistance to treatment, particularly in older populations. While therapeutic advances have been made, survival outcomes remain suboptimal. The evolution of DNA and RNA sequencing technologies, including whole-genome sequencing (WGS), whole-exome sequencing (WES), and RNA sequencing (RNA-Seq), has significantly enhanced our understanding of AML at the molecular level. These technologies have led to the discovery of driver mutations and transcriptomic alterations critical for improving diagnosis, prognosis, and personalized therapy development. Furthermore, single-cell RNA sequencing (scRNA-Seq) has uncovered rare subpopulations of leukemia stem cells (LSCs) contributing to disease progression and relapse. However, widespread clinical integration of these tools remains limited by costs, data complexity, and ethical challenges. This review explores recent advancements in DNA/RNA sequencing in AML and highlights both the potential and limitations of these techniques in clinical practice.
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Affiliation(s)
| | - Jiang Zhong
- Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA;
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Mansoor S, Hamid S, Tuan TT, Park JE, Chung YS. Advance computational tools for multiomics data learning. Biotechnol Adv 2024; 77:108447. [PMID: 39251098 DOI: 10.1016/j.biotechadv.2024.108447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 09/01/2024] [Accepted: 09/05/2024] [Indexed: 09/11/2024]
Abstract
The burgeoning field of bioinformatics has seen a surge in computational tools tailored for omics data analysis driven by the heterogeneous and high-dimensional nature of omics data. In biomedical and plant science research multi-omics data has become pivotal for predictive analytics in the era of big data necessitating sophisticated computational methodologies. This review explores a diverse array of computational approaches which play crucial role in processing, normalizing, integrating, and analyzing omics data. Notable methods such similarity-based methods, network-based approaches, correlation-based methods, Bayesian methods, fusion-based methods and multivariate techniques among others are discussed in detail, each offering unique functionalities to address the complexities of multi-omics data. Furthermore, this review underscores the significance of computational tools in advancing our understanding of data and their transformative impact on research.
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Affiliation(s)
- Sheikh Mansoor
- Department of Plant Resources and Environment, Jeju National University, 63243, Republic of Korea
| | - Saira Hamid
- Watson Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Pulwama, J&K, India
| | - Thai Thanh Tuan
- Department of Plant Resources and Environment, Jeju National University, 63243, Republic of Korea; Multimedia Communications Laboratory, University of Information Technology, Ho Chi Minh city 70000, Vietnam; Multimedia Communications Laboratory, Vietnam National University, Ho Chi Minh city 70000, Vietnam
| | - Jong-Eun Park
- Department of Animal Biotechnology, College of Applied Life Science, Jeju National University, Jeju, Jeju-do, Republic of Korea.
| | - Yong Suk Chung
- Department of Plant Resources and Environment, Jeju National University, 63243, Republic of Korea.
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Qi Q, Jiang Y, Zhou X, Lü Y, Xiao R, Bai J, Lou H, Sun W, Lian Y, Hao N, Li M, Chang J. Whole-genome sequencing analysis in fetal structural anomalies: novel phenotype-genotype discoveries. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2024; 63:664-671. [PMID: 37842862 DOI: 10.1002/uog.27517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 09/28/2023] [Accepted: 10/03/2023] [Indexed: 10/17/2023]
Abstract
OBJECTIVES The identification of structural variants and single-nucleotide variants is essential in finding molecular etiologies of monogenic genetic disorders. Whole-genome sequencing (WGS) is becoming more widespread in genetic disease diagnosis. However, data on its clinical utility remain limited in prenatal practice. We aimed to expand our understanding of implementing WGS in the genetic diagnosis of fetal structural anomalies. METHODS We employed trio WGS with a minimum coverage of 40× on the MGI DNBSEQ-T7 platform in a cohort of 17 fetuses presenting with aberrations detected by ultrasound, but uninformative findings of standard chromosomal microarray analysis (CMA) and exome sequencing (ES). RESULTS Causative genetic variants were identified in two families, with an increased diagnostic yield of 11.8% (2/17). Both were exon-level copy-number variants of small size (3.03 kb and 5.16 kb) and beyond the detection thresholds of CMA and ES. Moreover, to the best of our knowledge, we have described the first prenatal instance of the association of FGF8 with holoprosencephaly and facial deformities. CONCLUSIONS Our analysis demonstrates the clinical value of WGS in the diagnosis of the underlying etiology of fetuses with structural abnormalities, when routine genetic tests have failed to provide a diagnosis. Additionally, the novel variants and new fetal manifestations have expanded the mutational and phenotypic spectrums of BBS9 and FGF8. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
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Affiliation(s)
- Q Qi
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - Y Jiang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - X Zhou
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - Y Lü
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - R Xiao
- National Engineering Laboratory for Key Technology of Birth Defect Control and Prevention, Screening and Diagnostic R&D Center, Zhejiang, China
| | - J Bai
- Becreative Lab Co. Ltd, Beijing, China
| | - H Lou
- Becreative Lab Co. Ltd, Beijing, China
| | - W Sun
- Biosan Biochemical Technologies Co. Ltd., Zhejiang, China
| | - Y Lian
- Biosan Biochemical Technologies Co. Ltd., Zhejiang, China
| | - N Hao
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - M Li
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
| | - J Chang
- Department of Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
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Xia Y, Wang Z, Hu Y, Zhao P, Li J, Zhang L, Fang R, Zhao J. Isolation, Identification, Genomic Diversity, and Antimicrobial Resistance Analysis of Streptococcus suis in Hubei Province of China from 2021 to 2023. Microorganisms 2024; 12:917. [PMID: 38792744 PMCID: PMC11124115 DOI: 10.3390/microorganisms12050917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 04/17/2024] [Accepted: 04/26/2024] [Indexed: 05/26/2024] Open
Abstract
Streptococcus suis (S. suis) is a zoonotic pathogen capable of causing severe diseases in humans and pigs, including meningitis, sepsis, polyserositis, arthritis, and endocarditis. This study aimed to investigate the biological characteristics of 19 strains of S. suis isolated from diseased pigs in Hubei Province between 2021 and 2023. Through bioinformatics analysis, we investigated the serotype, MLST, pan-genome characteristics, SNP, AMR, and ICE of the 19 S. suis isolates. Among the 19 S. suis strains, ten serotypes were identified, and serotype 9 was the most prevalent (21.05%). Ten new alleles and nine new sequence types (STs) were discovered, with ST28 and ST243 emerging as the predominant STs. The results of the pan-genomic analysis of S. suis indicate that there are 943 core genes, 2259 shell genes, and 5663 cloud genes. Through SNP evolutionary analysis, we identified a strong genetic similarity between SS31 and the reference genome P1/7. The analysis of antibiotic resistance genes revealed widespread presence of erm(B) and tet(O) genes among 19 strains of S. suis. This association may be linked to the high resistance of S. suis to lincosamides, macrolides, and tetracyclines. Integrative and conjugative elements (ICEs) and integrative and mobilizable elements (IMEs) were identified in 16 strains, with a carriage rate of 84.21%, and resistance genes were identified within the ICE/IME elements of 8 strains. Antimicrobial susceptibility testing revealed that all strains showed sensitivity to vancomycin and lincomycin but resistance to tilmicosin, tiamulin, amoxicillin, and doxycycline. This study contributes to our understanding of the genomic diversity of S. suis in Hubei Province of China, providing essential data for the comprehensive prevention and control of S. suis infections in China.
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Affiliation(s)
- Yingjun Xia
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; (Y.X.); (Y.H.); (P.Z.); (J.L.); (L.Z.); (R.F.)
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China;
- Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China
| | - Zhaoyang Wang
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China;
- Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China
| | - Yanli Hu
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; (Y.X.); (Y.H.); (P.Z.); (J.L.); (L.Z.); (R.F.)
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China;
- Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China
| | - Pengfei Zhao
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; (Y.X.); (Y.H.); (P.Z.); (J.L.); (L.Z.); (R.F.)
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China;
- Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China
| | - Jianhai Li
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; (Y.X.); (Y.H.); (P.Z.); (J.L.); (L.Z.); (R.F.)
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China;
- Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China
| | - Li Zhang
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; (Y.X.); (Y.H.); (P.Z.); (J.L.); (L.Z.); (R.F.)
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China;
- Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China
| | - Rui Fang
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; (Y.X.); (Y.H.); (P.Z.); (J.L.); (L.Z.); (R.F.)
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China;
- Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China
| | - Junlong Zhao
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; (Y.X.); (Y.H.); (P.Z.); (J.L.); (L.Z.); (R.F.)
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China;
- Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China
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Schroeder C, Faust U, Krauße L, Liebmann A, Abele M, Demidov G, Schütz L, Kelemen O, Pohle A, Gauß S, Sturm M, Roggia C, Streiter M, Buchert R, Armenau-Ebinger S, Nann D, Beschorner R, Handgretinger R, Ebinger M, Lang P, Holzer U, Skokowa J, Ossowski S, Haack TB, Mau-Holzmann UA, Dufke A, Riess O, Brecht IB. Clinical trio genome sequencing facilitates the interpretation of variants in cancer predisposition genes in paediatric tumour patients. Eur J Hum Genet 2023; 31:1139-1146. [PMID: 37507557 PMCID: PMC10545765 DOI: 10.1038/s41431-023-01423-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 05/19/2023] [Accepted: 06/26/2023] [Indexed: 07/30/2023] Open
Abstract
The prevalence of pathogenic and likely pathogenic (P/LP) variants in genes associated with cancer predisposition syndromes (CPS) is estimated to be 8-18% for paediatric cancer patients. In more than half of the carriers, the family history is unsuspicious for CPS. Therefore, broad genetic testing could identify germline predisposition in additional children with cancer resulting in important implications for themselves and their families. We thus evaluated clinical trio genome sequencing (TGS) in a cohort of 72 paediatric patients with solid cancers other than retinoblastoma or CNS-tumours. The most prevalent cancer types were sarcoma (n = 26), neuroblastoma (n = 15), and nephroblastoma (n = 10). Overall, P/LP variants in CPS genes were identified in 18.1% of patients (13/72) and P/LP variants in autosomal-dominant CPS genes in 9.7% (7/72). Genetic evaluation would have been recommended for the majority of patients with P/LP variants according to the Jongmans criteria. Four patients (5.6%, 4/72) carried P/LP variants in autosomal-dominant genes known to be associated with their tumour type. With the immediate information on variant inheritance, TGS facilitated the identification of a de novo P/LP in NF1, a gonadosomatic mosaic in WT1 and two pathogenic variants in one patient (DICER1 and PALB2). TGS allows a more detailed characterization of structural variants with base-pair resolution of breakpoints which can be relevant for the interpretation of copy number variants. Altogether, TGS allows comprehensive identification of children with a CPS and supports the individualised clinical management of index patients and high-risk relatives.
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Affiliation(s)
- Christopher Schroeder
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
- Centre for Personalized Cancer Prevention, University Hospital Tübingen, Tübingen, Germany
| | - Ulrike Faust
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Luisa Krauße
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Alexandra Liebmann
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Michael Abele
- Department of Paediatric Haematology and Oncology, University Children's Hospital Tübingen, Tübingen, Germany
| | - German Demidov
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Leon Schütz
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Olga Kelemen
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Alexandra Pohle
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Silja Gauß
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Marc Sturm
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Cristiana Roggia
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Monika Streiter
- Department of Paediatric Haematology and Oncology, Children's Hospital Heilbronn, Heilbronn, Germany
| | - Rebecca Buchert
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Sorin Armenau-Ebinger
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Dominik Nann
- Institute of Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany
| | - Rudi Beschorner
- Institute of Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany
| | - Rupert Handgretinger
- Department of Paediatric Haematology and Oncology, University Children's Hospital Tübingen, Tübingen, Germany
| | - Martin Ebinger
- Department of Paediatric Haematology and Oncology, University Children's Hospital Tübingen, Tübingen, Germany
| | - Peter Lang
- Department of Paediatric Haematology and Oncology, University Children's Hospital Tübingen, Tübingen, Germany
| | - Ursula Holzer
- Department of Paediatric Haematology and Oncology, University Children's Hospital Tübingen, Tübingen, Germany
| | - Julia Skokowa
- Department of Oncology, Haematology, Immunology, Rheumatology, and Pulmonology, University Hospital Tübingen, Tübingen, Germany
| | - Stephan Ossowski
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Tobias B Haack
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Ulrike A Mau-Holzmann
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Andreas Dufke
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
| | - Olaf Riess
- Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany
- Centre for Personalized Cancer Prevention, University Hospital Tübingen, Tübingen, Germany
- NGS Core Centre Tübingen, University Tübingen, Tübingen, Germany
| | - Ines B Brecht
- Department of Paediatric Haematology and Oncology, University Children's Hospital Tübingen, Tübingen, Germany.
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11
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Boral J, Pınarlık F, Ekinci G, Can F, Ergönül Ö. Does Emerging Carbapenem Resistance in Acinetobacter baumannii Increase the Case Fatality Rate? Systematic Review and Meta-Analysis. Infect Dis Rep 2023; 15:564-575. [PMID: 37888136 PMCID: PMC10606343 DOI: 10.3390/idr15050055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 09/20/2023] [Accepted: 09/25/2023] [Indexed: 10/28/2023] Open
Abstract
BACKGROUND In the era of rising carbapenem resistance, we aimed to investigate the change in mortality rate and positivity of carbapenemase genes in Acinetobacter baumannii. METHODS Preferred Reporting Items for Systematic Review (PRISMA) guidelines were adopted in this systematic review. Our literature search included the Cochrane Library, Pubmed, Scopus, Web of Science, Medline, Tubitak TR Dizin, and Harman databases for studies dating back from 2003 to 2023 reporting bloodstream A. baumannii infections in Türkiye. A simple linear regression model was used to determine the association between resistance, mortality, and time. RESULTS A total of 1717 studies were identified through a literature search, and 21 articles were selected based on the availability of the data regarding mortality and resistance rate (four articles) or the molecular epidemiology of carbapenem-resistant A. baumannii (17 articles) in Türkiye. From 2007 to 2018, the carbapenem resistance rate increased (p = 0.025). The OXA-23 and OXA-58 positivities were inversely correlated (p = 0.025). CONCLUSIONS Despite the emergence of carbapenem resistance, mortality did not increase in parallel, which may be due to improved medical advancements or the fitness cost of bacteria upon prolonged antimicrobial exposure. Therefore, we suggest further global research with the foresight to assess clonal relatedness that might affect the carbapenem resistance rate.
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Affiliation(s)
- Jale Boral
- Graduate School of Health Sciences, Koç University, Istanbul 34010, Türkiye; (J.B.)
- Koç University İşBank Center for Infectious Diseases, Koç University Hospital (KUISCID), Istanbul 34010, Türkiye;
| | - Fatihan Pınarlık
- Graduate School of Health Sciences, Koç University, Istanbul 34010, Türkiye; (J.B.)
- Koç University İşBank Center for Infectious Diseases, Koç University Hospital (KUISCID), Istanbul 34010, Türkiye;
| | - Güz Ekinci
- Graduate School of Health Sciences, Koç University, Istanbul 34010, Türkiye; (J.B.)
- Koç University İşBank Center for Infectious Diseases, Koç University Hospital (KUISCID), Istanbul 34010, Türkiye;
| | - Füsun Can
- Koç University İşBank Center for Infectious Diseases, Koç University Hospital (KUISCID), Istanbul 34010, Türkiye;
- Department of Medical Microbiology, School of Medicine, Koç University, Istanbul 34010, Türkiye
| | - Önder Ergönül
- Koç University İşBank Center for Infectious Diseases, Koç University Hospital (KUISCID), Istanbul 34010, Türkiye;
- Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Koç University, Istanbul 34010, Türkiye
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12
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Reilly L, Seddighi S, Singleton AB, Cookson MR, Ward ME, Qi YA. Variant biomarker discovery using mass spectrometry-based proteogenomics. FRONTIERS IN AGING 2023; 4:1191993. [PMID: 37168844 PMCID: PMC10165118 DOI: 10.3389/fragi.2023.1191993] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 04/13/2023] [Indexed: 05/13/2023]
Abstract
Genomic diversity plays critical roles in risk of disease pathogenesis and diagnosis. While genomic variants-including single nucleotide variants, frameshift variants, and mis-splicing isoforms-are commonly detected at the DNA or RNA level, their translated variant protein or polypeptide products are ultimately the functional units of the associated disease. These products are often released in biofluids and could be leveraged for clinical diagnosis and patient stratification. Recent emergence of integrated analysis of genomics with mass spectrometry-based proteomics for biomarker discovery, also known as proteogenomics, have significantly advanced the understanding disease risk variants, precise medicine, and biomarker discovery. In this review, we discuss variant proteins in the context of cancers and neurodegenerative diseases, outline current and emerging proteogenomic approaches for biomarker discovery, and provide a comprehensive proteogenomic strategy for detection of putative biomarker candidates in human biospecimens. This strategy can be implemented for proteogenomic studies in any field of enquiry. Our review timely addresses the need of biomarkers for aging related diseases.
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Affiliation(s)
- Luke Reilly
- Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
| | - Sahba Seddighi
- National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
| | - Andrew B. Singleton
- Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
| | - Mark R. Cookson
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
| | - Michael E. Ward
- National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
| | - Yue A. Qi
- Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
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13
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Hayeems RZ, Bernier F, Boycott KM, Hartley T, Michaels-Igbokwe C, Marshall DA. Positioning whole exome sequencing in the diagnostic pathway for rare disease to optimise utility: a protocol for an observational cohort study and an economic evaluation. BMJ Open 2022; 12:e061468. [PMID: 36216418 PMCID: PMC9557316 DOI: 10.1136/bmjopen-2022-061468] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION Despite the superior diagnostic performance of exome and genome sequencing compared with conventional genetic tests, evidence gaps related to clinical utility and cost effectiveness have limited their availability in routine clinical practice in many jurisdictions. To inform adoption and reimbursement policy, this protocol provides a chain of evidence approach to determining the diagnostic utility, clinical utility and cost-effectiveness of whole exome sequencing (WES) from seven medical genetic centres in two Canadian provinces. METHODS AND ANALYSIS Using a multicentre observational cohort design, we will extract data specific to the pre-WES diagnostic pathway and 1-year post-WES medical management from electronic medical records for 650 patients with rare disease of suspected genetic aetiology who receive WES. The date from the clinical record will be linked to provincial administrative health database to capture healthcare resource use and estimate costs. Our analysis will: (1) define and describe diagnostic testing pathways that occur prior to WES among patients with rare disease, (2) determine the diagnostic utility of WES, characterised as the proportion of patients for whom causative DNA variants are identified, (3) determine the clinical utility of WES, characterised as a change in medical management triggered by WES results, (4) determine the pattern and cost of health service utilisation prior and 1 year following WES among patients who receive a diagnosis, do not receive a diagnosis, or receive an uncertain diagnosis and (5) estimate the cost-effectiveness of WES compared with conventional diagnostic testing pathways, measured by the incremental cost per additional patient diagnosed by WES using simulation modelling. ETHICS AND DISSEMINATION This protocol was approved by Clinical Trials Ontario (CTO-1577) and research ethics boards at the University of Calgary (REB18-0744 and REB20-1449) and University of Alberta (Pro0009156). Findings will be disseminated through academic publications and policy reports.
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Affiliation(s)
- Robin Z Hayeems
- Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
- Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Francois Bernier
- Department of Medical Genetics, Alberta Children's Hospital, Calgary, Alberta, Canada
- Cummings School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Kym M Boycott
- Department of Genetics, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
- Department of Paediatrics, Facuty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Taila Hartley
- Department of Genetics, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
| | - Christine Michaels-Igbokwe
- Cummings School of Medicine, University of Calgary, Calgary, Alberta, Canada
- O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada
| | - Deborah A Marshall
- Cummings School of Medicine, University of Calgary, Calgary, Alberta, Canada
- O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada
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14
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Gindin T, Hsiao SJ. Analytical Principles of Cancer Next Generation Sequencing. Clin Lab Med 2022; 42:395-408. [DOI: 10.1016/j.cll.2022.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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15
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Sodi R. Finding the broken helix: The mainstreaming of genomic medicine into clinical biochemistry. Ann Clin Biochem 2022; 59:159-161. [PMID: 35224982 DOI: 10.1177/00045632221080044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Ravinder Sodi
- Department of Clinical Biochemistry, University Hospitals Dorset & Bournemouth University, Dorset, UK
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16
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Kamp M, Krause A, Ramsay M. Has translational genomics come of age in Africa? Hum Mol Genet 2021; 30:R164-R173. [PMID: 34240178 DOI: 10.1093/hmg/ddab180] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/27/2021] [Accepted: 06/29/2021] [Indexed: 01/12/2023] Open
Abstract
The rapid increase in genomics research in Africa and the growing promise of precision public health begs the question of whether African genomics has come of age and is being translated into improved healthcare for Africans. An assessment of the continent's readiness suggests that genetic service delivery remains limited and extremely fragile. The paucity of data on mutation profiles for monogenic disorders and lack of large genome-wide association cohorts for complex traits in African populations is a significant barrier, coupled with extreme genetic variation across different regions and ethnic groups. Data from many different populations is essential to developing appropriate genetic services. Of the proposed genetic service delivery models currently used in Africa-Uncharacterized, Limited, Disease-focused, Emerging and Established-the first three best describe the situation in most African countries. Implementation is fraught with difficulties related to the scarcity of an appropriately skilled medical genetic workforce, limited infrastructure and processes, insufficient health funding and lack of political support, and overstretched health systems. There is a strong nucleus of determined and optimistic clinicians and scientists with a clear vision, and there is hope for innovative solutions and technological leapfrogging. However, a multi-dimensional approach with active interventions to stimulate genomic research, clinical genetics and overarching healthcare systems is needed to reduce genetic service inequalities and accelerate precision public health on the continent. Human and infrastructure capacity development, dedicated funding, political will and supporting legislation, and public education and awareness, are critical elements for success. Africa-relevant genomic and related health economics research remains imperative with an overarching need to translate knowledge into improved healthcare. Given the limited data and genetic services across most of Africa, the continent has not yet come of 'genomics' age.
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Affiliation(s)
- Michelle Kamp
- Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, The University of the Witwatersrand, National Health Laboratory Service, Johannesburg, 2193, South Africa.,Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa
| | - Amanda Krause
- Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, The University of the Witwatersrand, National Health Laboratory Service, Johannesburg, 2193, South Africa
| | - Michèle Ramsay
- Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, The University of the Witwatersrand, National Health Laboratory Service, Johannesburg, 2193, South Africa.,Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa
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17
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Cai W, Ji J, Wu B, Hao K, Ren P, Jin Y, Yang L, Tong Q, Shen Z. Characterization of the small RNA transcriptomes of cell protrusions and cell bodies of highly metastatic hepatocellular carcinoma cells via RNA sequencing. Oncol Lett 2021; 22:568. [PMID: 34113396 PMCID: PMC8185705 DOI: 10.3892/ol.2021.12829] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Accepted: 02/23/2021] [Indexed: 12/18/2022] Open
Abstract
Increasing evidence suggest that hepatocellular carcinoma (HCC) HCCLM3 cells initially develop pseudopodia when they metastasize, and microRNAs (miRNAs/miRs) and circular RNAs (circRNAs) have been demonstrated to serve important roles in the development, progression and metastasis of cancer. The present study aimed to isolate the cell bodies (CBs) and cell protrusions (CPs) from HCCLM3 cells, and screen the miRNAs and circRNAs associated with HCC infiltration and metastasis in CBs and CPs. The Boyden chamber assay has been confirmed to effectively isolate the CBs and CPs from HCCLM3 cells via observation of microtubule immunofluorescence, DAPI staining and nuclear protein H3 western blotting. Following high-throughput sequencing of the successfully isolated CBs and CPs, 64 pairs of miRNAs, including 23 pairs of upregulated genes and 41 pairs of downregulated genes, and 260 sets of circRNAs, including 127 upregulated genes and 133 downregulated genes, were significantly differentially expressed, using the following criteria: HP/HB ratio, fold change ≥|1.5|, P<0.05). PCR analysis verified that changes in the expression levels of hsa-let-7a-5p, hsa-let-7c-3p, hsa-miR-30c-5p, hsa_circ_0059580, hsa_circ_0067475, hsa_circ_0002100 and hsa_circ_00072309 were consistent with the sequencing results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to analyze the functions and roles of the differentially expressed miRNAs and circRNAs. The interaction maps between miRNAs and circRNAs were constructed, and signaling pathway maps were analyzed to determine the molecular mechanism and regulation of the differentially expressed miRNAs and circRNAs. Taken together, the results of the present study suggest that the Boyden chamber assay can be used to effectively isolate the somatic CBs and CPs of HCC, which can be used to screen the miRNAs and circRNAs associated with invasion and metastasis of HCC.
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Affiliation(s)
- Wenpin Cai
- Department of Laboratory Medicine, Wen Zhou Traditional Chinese Medicine Hospital, Wenzhou, Zhejiang 325035, P.R. China
| | - Jingzhang Ji
- Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
| | - Biting Wu
- Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
| | - Kaixuan Hao
- Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
| | - Ping Ren
- Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
| | - Yu Jin
- Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
| | - Lihong Yang
- Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
| | - Qingchao Tong
- Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
| | - Zhifa Shen
- Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
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18
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Shanmugakani RK, Srinivasan B, Glesby MJ, Westblade LF, Cárdenas WB, Raj T, Erickson D, Mehta S. Current state of the art in rapid diagnostics for antimicrobial resistance. LAB ON A CHIP 2020; 20:2607-2625. [PMID: 32644060 PMCID: PMC7428068 DOI: 10.1039/d0lc00034e] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
Abstract
Antimicrobial resistance (AMR) is a fundamental global concern analogous to climate change threatening both public health and global development progress. Infections caused by antimicrobial-resistant pathogens pose serious threats to healthcare and human capital. If the increasing rate of AMR is left uncontrolled, it is estimated that it will lead to 10 million deaths annually by 2050. This global epidemic of AMR necessitates radical interdisciplinary solutions to better detect antimicrobial susceptibility and manage infections. Rapid diagnostics that can identify antimicrobial-resistant pathogens to assist clinicians and health workers in initiating appropriate treatment are critical for antimicrobial stewardship. In this review, we summarize different technologies applied for the development of rapid diagnostics for AMR and antimicrobial susceptibility testing (AST). We briefly describe the single-cell technologies that were developed to hasten the AST of infectious pathogens. Then, the different types of genotypic and phenotypic techniques and the commercially available rapid diagnostics for AMR are discussed in detail. We conclude by addressing the potential of current rapid diagnostic systems being developed as point-of-care (POC) diagnostic tools and the challenges to adapt them at the POC level. Overall, this review provides an insight into the current status of rapid and POC diagnostic systems for AMR.
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Affiliation(s)
- Rathina Kumar Shanmugakani
- Institute for Nutritional Sciences, Global Health, and Technology, Cornell University, Ithaca, New York, USA
- Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
| | - Balaji Srinivasan
- Institute for Nutritional Sciences, Global Health, and Technology, Cornell University, Ithaca, New York, USA
- Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
| | - Marshall J. Glesby
- Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Lars F. Westblade
- Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Washington B. Cárdenas
- Laboratorio para Investigaciones Biomédicas, Escuela Superior Politécnica del Litoral, Guayaquil, Guayas, Ecuador
| | - Tony Raj
- St. John’s Research Institute, Bangalore, Karnataka, India
| | - David Erickson
- Institute for Nutritional Sciences, Global Health, and Technology, Cornell University, Ithaca, New York, USA
- Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
- Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York, USA
| | - Saurabh Mehta
- Institute for Nutritional Sciences, Global Health, and Technology, Cornell University, Ithaca, New York, USA
- Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
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19
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Murphy NM, Samarasekera TS, Macaskill L, Mullen J, Rombauts LJF. Genome sequencing of human in vitro fertilisation embryos for pathogenic variation screening. Sci Rep 2020; 10:3795. [PMID: 32123222 PMCID: PMC7052235 DOI: 10.1038/s41598-020-60704-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 02/13/2020] [Indexed: 12/22/2022] Open
Abstract
Whole-genome sequencing of preimplantation human embryos to detect and screen for genetic diseases is a technically challenging extension to preconception screening. Combining preconception genetic screening with preimplantation testing of human embryos facilitates the detection of de novo mutations and self-validates transmitted variant detection in both the reproductive couple and the embryo’s samples. Here we describe a trio testing workflow that involves whole-genome sequencing of amplified DNA from biopsied embryo trophectoderm cells and genomic DNA from both parents. Variant prediction software and annotation databases were used to assess variants of unknown significance and previously not described de novo variants in five single-gene preimplantation genetic testing couples and eleven of their embryos. Pathogenic variation, tandem repeat, copy number and structural variations were examined against variant calls for compound heterozygosity and predicted disease status was ascertained. Multiple trio testing showed complete concordance with known variants ascertained by single-nucleotide polymorphism array and uncovered de novo and transmitted pathogenic variants. This pilot study describes a method of whole-genome sequencing and analysis for embryo selection in high-risk couples to prevent early life fatal genetic conditions that adversely affect the quality of life of the individual and families.
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Affiliation(s)
- Nicholas M Murphy
- Genetic Technologies Ltd., Victoria, Australia. .,Monash IVF, Clayton, Victoria, Australia. .,GenEmbryomics Pty. Ltd., Victoria, Australia. .,Drug Delivery Disposition and Dynamics, Faculty of Pharmacy and Pharmaceutical Sciences, Parkville, Melbourne, Victoria, Australia.
| | | | | | | | - Luk J F Rombauts
- Monash IVF, Clayton, Victoria, Australia.,Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, Victoria, Australia.,Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.,Monash Women's & Newborn Program, Monash Health, Victoria, Australia
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20
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Abramczyk H, Brozek-Pluska B, Jarota A, Surmacki J, Imiela A, Kopec M. A look into the use of Raman spectroscopy for brain and breast cancer diagnostics: linear and non-linear optics in cancer research as a gateway to tumor cell identity. Expert Rev Mol Diagn 2020; 20:99-115. [PMID: 32013616 DOI: 10.1080/14737159.2020.1724092] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 01/28/2020] [Indexed: 12/14/2022]
Abstract
Introduction: Currently, intensely developing of linear and non-linear optical methods for cancer detection provides a valuable tool to improve sensitivity and specificity. One of the main reasons for insufficient progress in cancer diagnostics is related to the fact that most cancer types are not only heterogeneous in their genetic composition but also reside in varying microenvironments and interact with different cell types. Until now, no technology has been fully proven for effective detecting of invasive cancer, which infiltrating the extracellular matrix.Areas covered: This review investigates the current status of Raman spectroscopy and Raman imaging for brain and breast cancer diagnostics. Moreover, the review provides a comprehensive overview of the applicability of atomic force microscopy (AFM), linear and non-linear optics in cancer research as a gateway to tumor cell identity.Expert commentary: A combination of linear and non-linear optics, particularly Raman-driven methods, has many additional advantages to identify alterations in cancer cells that are crucial for their proliferation and that distinguish them from normal cells.
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Affiliation(s)
- Halina Abramczyk
- Laboratory of Laser Molecular Spectroscopy, Lodz University of Technology, Lodz, Poland
| | - Beata Brozek-Pluska
- Laboratory of Laser Molecular Spectroscopy, Lodz University of Technology, Lodz, Poland
| | - Arkadiusz Jarota
- Laboratory of Laser Molecular Spectroscopy, Lodz University of Technology, Lodz, Poland
| | - Jakub Surmacki
- Laboratory of Laser Molecular Spectroscopy, Lodz University of Technology, Lodz, Poland
| | - Anna Imiela
- Laboratory of Laser Molecular Spectroscopy, Lodz University of Technology, Lodz, Poland
| | - Monika Kopec
- Laboratory of Laser Molecular Spectroscopy, Lodz University of Technology, Lodz, Poland
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21
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Linderman MD, McElroy L, Chang L. MySeq: privacy-protecting browser-based personal Genome analysis for genomics education and exploration. BMC Med Genomics 2019; 12:172. [PMID: 31775760 PMCID: PMC6882182 DOI: 10.1186/s12920-019-0615-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 11/08/2019] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND The complexity of genome informatics is a recurring challenge for genome exploration and analysis by students and other non-experts. This complexity creates a barrier to wider implementation of experiential genomics education, even in settings with substantial computational resources and expertise. Reducing the need for specialized software tools will increase access to hands-on genomics pedagogy. RESULTS MySeq is a React.js single-page web application for privacy-protecting interactive personal genome analysis. All analyses are performed entirely in the user's web browser eliminating the need to install and use specialized software tools or to upload sensitive data to an external web service. MySeq leverages Tabix-indexing to efficiently query whole genome-scale variant call format (VCF) files stored locally or available remotely via HTTP(s) without loading the entire file. MySeq currently implements variant querying and annotation, physical trait prediction, pharmacogenomic, polygenic disease risk and ancestry analyses to provide representative pedagogical examples; and can be readily extended with new analysis or visualization components. CONCLUSIONS MySeq supports multiple pedagogical approaches including independent exploration and interactive online tutorials. MySeq has been successfully employed in an undergraduate human genome analysis course where it reduced the barriers-to-entry for hands-on human genome analysis.
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Affiliation(s)
| | - Leo McElroy
- Department of Computer Science, Middlebury College, Middlebury, VT USA
| | - Laura Chang
- Department of Computer Science, Middlebury College, Middlebury, VT USA
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22
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Ignatieva EV, Yurchenko AA, Voevoda MI, Yudin NS. Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population. BMC Med Genomics 2019; 12:61. [PMID: 31122248 PMCID: PMC6533173 DOI: 10.1186/s12920-019-0503-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Tick-borne encephalitis (TBE) is a viral infectious disease caused by tick-borne encephalitis virus (TBEV). TBEV infection is responsible for a variety of clinical manifestations ranging from mild fever to severe neurological illness. Genetic factors involved in the host response to TBEV that may potentially play a role in the severity of the disease are still poorly understood. In this study, using whole-exome sequencing, we aimed to identify genetic variants and genes associated with severe forms of TBE as well as biological pathways through which the identified variants may influence the severity of the disease. Results Whole-exome sequencing data analysis was performed on 22 Russian patients with severe forms of TBE and 17 Russian individuals from the control group. We identified 2407 candidate genes harboring rare, potentially pathogenic variants in exomes of patients with TBE and not containing any rare, potentially pathogenic variants in exomes of individuals from the control group. According to DAVID tool, this set of 2407 genes was enriched with genes involved in extracellular matrix proteoglycans pathway and genes encoding proteins located at the cell periphery. A total of 154 genes/proteins from these functional groups have been shown to be involved in protein-protein interactions (PPIs) with the known candidate genes/proteins extracted from TBEVHostDB database. By ranking these genes according to the number of rare harmful minor alleles, we identified two genes (MSR1 and LMO7), harboring five minor alleles, and three genes (FLNA, PALLD, PKD1) harboring four minor alleles. When considering genes harboring genetic variants associated with severe forms of TBE at the suggestive P-value < 0.01, 46 genes containing harmful variants were identified. Out of these 46 genes, eight (MAP4, WDFY4, ACTRT2, KLHL25, MAP2K3, MBD1, OR10J1, and OR2T34) were additionally found among genes containing rare pathogenic variants identified in patients with TBE; and five genes (WDFY4,ALK, MAP4, BNIPL, EPPK1) were found to encode proteins that are involved in PPIs with proteins encoded by genes from TBEVHostDB. Three genes out of five (MAP4, EPPK1, ALK) were found to encode proteins located at cell periphery. Conclusions Whole-exome sequencing followed by systems biology approach enabled to identify eight candidate genes (MAP4, WDFY4, ACTRT2, KLHL25, MAP2K3, MBD1, OR10J1, and OR2T34) that can potentially determine predisposition to severe forms of TBE. Analyses of the genetic risk factors for severe forms of TBE revealed a significant enrichment with genes controlling extracellular matrix proteoglycans pathway as well as genes encoding components of cell periphery. Electronic supplementary material The online version of this article (10.1186/s12920-019-0503-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Elena V Ignatieva
- Laboratory of Evolutionary Bioinformatics and Theoretical Genetics, The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia. .,Novosibirsk State University, Novosibirsk, 630090, Russia.
| | - Andrey A Yurchenko
- Laboratory of Infectious Disease Genomics, The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia
| | - Mikhail I Voevoda
- Novosibirsk State University, Novosibirsk, 630090, Russia.,Research Institute of Internal and Preventive Medicine-Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, 630004, Russia
| | - Nikolay S Yudin
- Laboratory of Infectious Disease Genomics, The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.,Novosibirsk State University, Novosibirsk, 630090, Russia
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23
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Zhang M, Dou H, Yang D, Shan M, Li X, Hao C, Zhang Y, Zeng P, He Y, Liu Y, Fu J, Wang W, Hu M, Li H, Tian Q, Lei S, Zhang L. Retrospective analysis of glycan-related biomarkers based on clinical laboratory data in two medical centers during the past 6 years. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2019; 162:141-163. [PMID: 30905446 DOI: 10.1016/bs.pmbts.2019.01.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Most of clinically used cancer biomarkers are either specific glycan structures or glycoproteins. Although the high serum levels of the cancer biomarkers are also present in certain patients suffering noncancer diseases, systematic measurement and comparison of the serum levels of all cancer biomarkers among cancer and noncancer patients have not been reported. In this study, the serum levels of 17 glucose and glycan-related biomarkers including 10 cancer biomarkers SCCA, CA724, CA50, CA242, CA125, CA199, CA153, AFP, CEA, and PSA were retrospectively investigated based on clinical laboratory data in two medical centers during the past 6 years (2012-2018). The data included a total of 1,477,309 clinical lab test results of 17 biomarkers from healthy controls and patients suffering 64 different types of cancer and noncancer diseases. We found that the median serum levels of CA724, CEA, CA153, SCCA, and CA125 were highest not in cancer patients but in patients suffering gout, lung fibrosis, nephrotic syndrome, uremia, and cirrhosis, respectively. Consistently, the classical ovarian cancer biomarker CA125 had better overall sensitivity and specificity as biomarker for cirrhosis (67% and 92%, respectively) than that for ovarian cancer (41% and 97%, respectively). Furthermore, the information shown as heatmap or waterfall built on the -Log10p values of the 17 glycan-related biomarkers in different clinically defined diseases suggested that all glycan-related biomarkers had cancer-, aging-, and disease-relevant characteristics and cancers were systems disease. The detailed presentation of the data for each of the 17 biomarkers will be deliberated in chapters 6-23 in this book series.
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Affiliation(s)
- Meng Zhang
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China.
| | - Huaiqian Dou
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China
| | - Dandan Yang
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China
| | - Ming Shan
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China
| | - Xiulian Li
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China
| | - Cui Hao
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China
| | - Yiran Zhang
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China
| | - Pengjiao Zeng
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China
| | - Yanli He
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China
| | - Yong Liu
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China
| | - Jing Fu
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China
| | - Wei Wang
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, China
| | - Minghui Hu
- Clinical Laboratory, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hui Li
- Clinical Laboratory, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Qingwu Tian
- Clinical Laboratory, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shuhe Lei
- College of Mathematical Sciences, Ocean University of China, Qingdao, China
| | - Lijuan Zhang
- Systems Biology and Medicine Center for Complex Diseases, Ocean University of China, Qingdao, China.
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24
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Wang Q, Peng WX, Wang L, Ye L. Toward multiomics-based next-generation diagnostics for precision medicine. Per Med 2019; 16:157-170. [PMID: 30816060 DOI: 10.2217/pme-2018-0085] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Our healthcare system is experiencing a paradigm shift to precision medicine, aiming at an early prediction of individual disease risks and targeted interventions. Whole-genome sequencing is currently gaining momentum, as it has the potential to capture all classes of genetic variation, thus providing a more complete picture of the individual's genetic makeup, which could be utilized in genetic testing; however, this will also lead to difficulties in interpreting the test results, necessitating careful integration of genomic data with other layers of information, both molecular multiomics measurements of epigenome, transcriptome, proteome, metabolome and even microbiome, as well as comprehensive information on diet, lifestyle and environment. Overall, the translation of patient-specific data into actionable diagnostic tools will be a challenging task, requiring expertise from multiple disciplines, secure data sharing in large reference databases and a strong computational infrastructure.
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Affiliation(s)
- Qi Wang
- Department of Emergency Medicine, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310007, Zhejiang Province, China
| | - Wei-Xian Peng
- Department of Emergency Medicine, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310007, Zhejiang Province, China
| | - Lu Wang
- Department of Emergency Medicine, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310007, Zhejiang Province, China
| | - Li Ye
- Department of Nursing, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
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25
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Berberich AJ, Hegele RA. The role of genetic testing in dyslipidaemia. Pathology 2019; 51:184-192. [DOI: 10.1016/j.pathol.2018.10.014] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 10/08/2018] [Accepted: 10/10/2018] [Indexed: 01/28/2023]
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26
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Supernat A, Vidarsson OV, Steen VM, Stokowy T. Comparison of three variant callers for human whole genome sequencing. Sci Rep 2018; 8:17851. [PMID: 30552369 PMCID: PMC6294778 DOI: 10.1038/s41598-018-36177-7] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 11/13/2018] [Indexed: 12/30/2022] Open
Abstract
Testing of patients with genetics-related disorders is in progress of shifting from single gene assays to gene panel sequencing, whole-exome sequencing (WES) and whole-genome sequencing (WGS). Since WGS is unquestionably becoming a new foundation for molecular analyses, we decided to compare three currently used tools for variant calling of human whole genome sequencing data. We tested DeepVariant, a new TensorFlow machine learning-based variant caller, and compared this tool to GATK 4.0 and SpeedSeq, using 30×, 15× and 10× WGS data of the well-known NA12878 DNA reference sample. According to our comparison, the performance on SNV calling was almost similar in 30× data, with all three variant callers reaching F-Scores (i.e. harmonic mean of recall and precision) equal to 0.98. In contrast, DeepVariant was more precise in indel calling than GATK and SpeedSeq, as demonstrated by F-Scores of 0.94, 0.90 and 0.84, respectively. We conclude that the DeepVariant tool has great potential and usefulness for analysis of WGS data in medical genetics.
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Affiliation(s)
- Anna Supernat
- Laboratory of Cell Biology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland
| | | | - Vidar M Steen
- NORMENT & K.J. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway
- Dr. E. Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway
| | - Tomasz Stokowy
- Computational Biology Unit, Institute of Informatics, University of Bergen, Bergen, Norway.
- NORMENT & K.J. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
- Dr. E. Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
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27
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Giau VV, Bagyinszky E, An SSA, Kim S. Clinical genetic strategies for early onset neurodegenerative diseases. Mol Cell Toxicol 2018. [DOI: 10.1007/s13273-018-0015-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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28
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Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature. Genet Med 2018; 20:1122-1130. [PMID: 29446766 DOI: 10.1038/gim.2017.247] [Citation(s) in RCA: 361] [Impact Index Per Article: 51.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 11/27/2017] [Indexed: 12/14/2022] Open
Abstract
PURPOSE We conducted a systematic literature review to summarize the current health economic evidence for whole-exome sequencing (WES) and whole-genome sequencing (WGS). METHODS Relevant studies were identified in the EMBASE, MEDLINE, Cochrane Library, EconLit and University of York Centre for Reviews and Dissemination databases from January 2005 to July 2016. Publications were included in the review if they were economic evaluations, cost studies, or outcome studies. RESULTS Thirty-six studies met our inclusion criteria. These publications investigated the use of WES and WGS in a variety of genetic conditions in clinical practice, the most common being neurological or neurodevelopmental disorders. Study sample size varied from a single child to 2,000 patients. Cost estimates for a single test ranged from $555 to $5,169 for WES and from $1,906 to $24,810 for WGS. Few cost analyses presented data transparently and many publications did not state which components were included in cost estimates. CONCLUSION The current health economic evidence base to support the more widespread use of WES and WGS in clinical practice is very limited. Studies that carefully evaluate the costs, effectiveness, and cost-effectiveness of these tests are urgently needed to support their translation into clinical practice.
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29
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Dunn P, Albury CL, Maksemous N, Benton MC, Sutherland HG, Smith RA, Haupt LM, Griffiths LR. Next Generation Sequencing Methods for Diagnosis of Epilepsy Syndromes. Front Genet 2018; 9:20. [PMID: 29467791 PMCID: PMC5808353 DOI: 10.3389/fgene.2018.00020] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 01/16/2018] [Indexed: 12/28/2022] Open
Abstract
Epilepsy is a neurological disorder characterized by an increased predisposition for seizures. Although this definition suggests that it is a single disorder, epilepsy encompasses a group of disorders with diverse aetiologies and outcomes. A genetic basis for epilepsy syndromes has been postulated for several decades, with several mutations in specific genes identified that have increased our understanding of the genetic influence on epilepsies. With 70-80% of epilepsy cases identified to have a genetic cause, there are now hundreds of genes identified to be associated with epilepsy syndromes which can be analyzed using next generation sequencing (NGS) techniques such as targeted gene panels, whole exome sequencing (WES) and whole genome sequencing (WGS). For effective use of these methodologies, diagnostic laboratories and clinicians require information on the relevant workflows including analysis and sequencing depth to understand the specific clinical application and diagnostic capabilities of these gene sequencing techniques. As epilepsy is a complex disorder, the differences associated with each technique influence the ability to form a diagnosis along with an accurate detection of the genetic etiology of the disorder. In addition, for diagnostic testing, an important parameter is the cost-effectiveness and the specific diagnostic outcome of each technique. Here, we review these commonly used NGS techniques to determine their suitability for application to epilepsy genetic diagnostic testing.
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Affiliation(s)
- Paul Dunn
- Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
| | - Cassie L Albury
- Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
| | - Neven Maksemous
- Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
| | - Miles C Benton
- Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
| | - Heidi G Sutherland
- Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
| | - Robert A Smith
- Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
| | - Larisa M Haupt
- Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
| | - Lyn R Griffiths
- Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
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30
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Abstract
Technologies such as next-generation sequencing and chromosomal microarray have advanced the understanding of the molecular pathogenesis of a variety of renal disorders. Genetic findings are increasingly used to inform the clinical management of many nephropathies, enabling targeted disease surveillance, choice of therapy, and family counselling. Genetic analysis has excellent diagnostic utility in paediatric nephrology, as illustrated by sequencing studies of patients with congenital anomalies of the kidney and urinary tract and steroid-resistant nephrotic syndrome. Although additional investigation is needed, pilot studies suggest that genetic testing can also provide similar diagnostic insight among adult patients. Reaching a genetic diagnosis first involves choosing the appropriate testing modality, as guided by the clinical presentation of the patient and the number of potential genes associated with the suspected nephropathy. Genome-wide sequencing increases diagnostic sensitivity relative to targeted panels, but holds the challenges of identifying causal variants in the vast amount of data generated and interpreting secondary findings. In order to realize the promise of genomic medicine for kidney disease, many technical, logistical, and ethical questions that accompany the implementation of genetic testing in nephrology must be addressed. The creation of evidence-based guidelines for the utilization and implementation of genetic testing in nephrology will help to translate genetic knowledge into improved clinical outcomes for patients with kidney disease.
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Affiliation(s)
- Emily E Groopman
- Division of Nephrology, Columbia University College of Physicians and Surgeons, 1150 Saint Nicholas Avenue, Russ Berrie Pavilion #412C, New York, New York 10032, USA
| | - Hila Milo Rasouly
- Division of Nephrology, Columbia University College of Physicians and Surgeons, 1150 Saint Nicholas Avenue, Russ Berrie Pavilion #412C, New York, New York 10032, USA
| | - Ali G Gharavi
- Division of Nephrology, Columbia University College of Physicians and Surgeons, 1150 Saint Nicholas Avenue, Russ Berrie Pavilion #412C, New York, New York 10032, USA
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31
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Biswas C, Chen SCA, Halliday C, Martinez E, Rockett RJ, Wang Q, Timms VJ, Dhakal R, Sadsad R, Kennedy KJ, Playford G, Marriott DJ, Slavin MA, Sorrell TC, Sintchenko V. Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance. J Vis Exp 2017. [PMID: 29364212 DOI: 10.3791/56714] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Candida glabrata can rapidly acquire mutations that result in drug resistance, especially to azoles and echinocandins. Identification of genetic mutations is essential, as resistance detected in vitro can often be correlated with clinical failure. We examined the feasibility of using whole genome sequencing (WGS) for genome-wide analysis of antifungal drug resistance in C. glabrata. The aim was torecognize enablers and barriers in the implementation WGS and measure its effectiveness. This paper outlines the key quality control checkpoints and essential components of WGS methodology to investigate genetic markers associated with reduced susceptibility to antifungal agents. It also estimates the accuracy of data analysis and turn-around-time of testing. Phenotypic susceptibility of 12 clinical, and one ATCC strain of C. glabrata was determined through antifungal susceptibility testing. These included three isolate pairs, from three patients, that developed rise in drug minimum inhibitory concentrations. In two pairs, the second isolate of each pair developed resistance to echinocandins. The second isolate of the third pair developed resistance to 5-flucytosine. The remaining comprised of susceptible and azole resistant isolates. Single nucleotide polymorphisms (SNPs) in genes linked to echinocandin, azole and 5-flucytosine resistance were confirmed in resistant isolates through WGS using the next generation sequencing. Non-synonymous SNPs in antifungal resistance genes such as FKS1, FKS2, CgPDR1, CgCDR1 and FCY2 were identified. Overall, an average of 98% of the WGS reads of C. glabrata isolates mapped to the reference genome with about 75-fold read depth coverage. The turnaround time and cost were comparable to Sanger sequencing. In conclusion, WGS of C. glabrata was feasible in revealing clinically significant gene mutations involved in resistance to different antifungal drug classes without the need for multiple PCR/DNA sequencing reactions. This represents a positive step towards establishing WGS capability in the clinical laboratory for simultaneous detection of antifungal resistance conferring substitutions.
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Affiliation(s)
- Chayanika Biswas
- Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital;
| | - Sharon C-A Chen
- Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital; Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR; Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney
| | - Catriona Halliday
- Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital; Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR
| | - Elena Martinez
- Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital
| | - Rebecca J Rockett
- Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital
| | - Qinning Wang
- Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital
| | - Verlaine J Timms
- Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital
| | - Rajat Dhakal
- Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital
| | - Rosemarie Sadsad
- Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital
| | - Karina J Kennedy
- Department of Microbiology and Infectious Diseases, Canberra Hospital and Health Services, Australian National University Medical School
| | - Geoffrey Playford
- Department of Microbiology and Infectious Diseases, Canberra Hospital and Health Services, Australian National University Medical School; Infection Management Services, Australian National University Medical School
| | - Deborah J Marriott
- Department of Microbiology and Infectious Diseases, St. Vincent's Hospital
| | - Monica A Slavin
- Department of Infectious Diseases, Peter MacCallum Cancer Centre
| | - Tania C Sorrell
- Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital; Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney
| | - Vitali Sintchenko
- Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital; Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR; Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney
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Wilson BJ, Miller FA, Rousseau F. Controversy and debate on clinical genomics sequencing—paper 1: genomics is not exceptional: rigorous evaluations are necessary for clinical applications of genomic sequencing. J Clin Epidemiol 2017; 92:4-6. [DOI: 10.1016/j.jclinepi.2017.08.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Revised: 07/22/2017] [Accepted: 08/24/2017] [Indexed: 10/18/2022]
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33
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Jose de Carli G, Campos Pereira T. On human parthenogenesis. Med Hypotheses 2017; 106:57-60. [DOI: 10.1016/j.mehy.2017.07.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Accepted: 07/07/2017] [Indexed: 12/15/2022]
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Dimitrakopoulos L, Prassas I, Berns EMJJ, Foekens JA, Diamandis EP, Charames GS. Variant peptide detection utilizing mass spectrometry: laying the foundations for proteogenomic identification and validation. Clin Chem Lab Med 2017; 55:1291-1304. [PMID: 28157690 DOI: 10.1515/cclm-2016-0947] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 12/07/2016] [Indexed: 01/29/2023]
Abstract
BACKGROUND Proteogenomics is an emerging field at the intersection of genomics and proteomics. Many variant peptides corresponding to single nucleotide variations (SNVs) are associated with specific diseases. The aim of this study was to demonstrate the feasibility of proteogenomic-based variant peptide detection in disease models and clinical specimens. METHODS We sought to detect p53 single amino acid variant (SAAV) peptides in breast cancer tumor samples that have been previously subjected to sequencing analysis. Initially, two cancer cell lines having a cellular tumor antigen p53 (TP53) mutation and one wild type for TP53 were analyzed by selected reaction monitoring (SRM) assays as controls. One pool of wild type and one pool of mutated for TP53 cytosolic extracts were assayed with a shotgun proteogenomic workflow. Furthermore, 18 individual samples having a mutation in TP53 were assayed by SRM. RESULTS Two mutant p53 peptides were successfully detected in two cancer cell lines as expected from their DNA sequence. Wild type p53 peptides were detected in both cytosolic pools, however, none of the mutant p53 peptides were identified. Mutations at the protein level were detected in two cytosolic extracts and whole tumor lysates from the same patients by SRM analysis. Six thousand and six hundred and twenty eight non-redundant proteins were identified in the two cytosolic pools, thus greatly improving a previously reported cytosolic proteome. CONCLUSIONS In the current study we show the great potential of using proteogenomics for the direct identification of cancer-associated mutations in clinical samples and we discuss current limitations and future perspectives.
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Zhang W, Wang X, Xia Y, Ouyang Z. Ambient Ionization and Miniature Mass Spectrometry Systems for Disease Diagnosis and Therapeutic Monitoring. Theranostics 2017; 7:2968-2981. [PMID: 28839457 PMCID: PMC5566099 DOI: 10.7150/thno.19410] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 06/06/2017] [Indexed: 12/26/2022] Open
Abstract
Mass spectrometry has become a powerful tool in the field of biomedicine. The combination of ambient ionization and miniature mass spectrometry systems could most likely fulfill a significant need in medical diagnostics, providing highly specific molecular information in real time for clinical and even point-of-care analysis. In this review, we discuss the recent development of ambient ionization and miniature mass spectrometers as well as their potential in disease diagnosis and therapeutic monitoring, with an emphasis on their capability in analysis of biofluids and tissues. We also speculate the future development of the integrated, miniature MS systems and provide our perspectives on the challenges in technical development as well as possible solutions for path forward.
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Affiliation(s)
- Wenpeng Zhang
- State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
| | - Xiao Wang
- State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
| | - Yu Xia
- Department of Chemistry, Tsinghua University, Beijing 10084, China
- Department of Chemistry, Purdue University, West Lafayette, IN 47906, USA
| | - Zheng Ouyang
- State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
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Forbes JD, Knox NC, Ronholm J, Pagotto F, Reimer A. Metagenomics: The Next Culture-Independent Game Changer. Front Microbiol 2017; 8:1069. [PMID: 28725217 PMCID: PMC5495826 DOI: 10.3389/fmicb.2017.01069] [Citation(s) in RCA: 206] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 05/29/2017] [Indexed: 02/01/2023] Open
Abstract
A trend towards the abandonment of obtaining pure culture isolates in frontline laboratories is at a crossroads with the ability of public health agencies to perform their basic mandate of foodborne disease surveillance and response. The implementation of culture-independent diagnostic tests (CIDTs) including nucleic acid and antigen-based assays for acute gastroenteritis is leaving public health agencies without laboratory evidence to link clinical cases to each other and to food or environmental substances. This limits the efficacy of public health epidemiology and surveillance as well as outbreak detection and investigation. Foodborne outbreaks have the potential to remain undetected or have insufficient evidence to support source attribution and may inadvertently increase the incidence of foodborne diseases. Next-generation sequencing of pure culture isolates in clinical microbiology laboratories has the potential to revolutionize the fields of food safety and public health. Metagenomics and other 'omics' disciplines could provide the solution to a cultureless future in clinical microbiology, food safety and public health. Data mining of information obtained from metagenomics assays can be particularly useful for the identification of clinical causative agents or foodborne contamination, detection of AMR and/or virulence factors, in addition to providing high-resolution subtyping data. Thus, metagenomics assays may provide a universal test for clinical diagnostics, foodborne pathogen detection, subtyping and investigation. This information has the potential to reform the field of enteric disease diagnostics and surveillance and also infectious diseases as a whole. The aim of this review will be to present the current state of CIDTs in diagnostic and public health laboratories as they relate to foodborne illness and food safety. Moreover, we will also discuss the diagnostic and subtyping utility and concomitant bias limitations of metagenomics and comparable detection techniques in clinical microbiology, food and public health laboratories. Early advances in the discipline of metagenomics, however, have indicated noteworthy challenges. Through forthcoming improvements in sequencing technology and analytical pipelines among others, we anticipate that within the next decade, detection and characterization of pathogens via metagenomics-based workflows will be implemented in routine usage in diagnostic and public health laboratories.
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Affiliation(s)
- Jessica D. Forbes
- National Microbiology Laboratory, Public Health Agency of Canada, WinnipegMB, Canada
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, WinnipegMB, Canada
| | - Natalie C. Knox
- National Microbiology Laboratory, Public Health Agency of Canada, WinnipegMB, Canada
| | - Jennifer Ronholm
- Department of Food Science and Agricultural Chemistry, Faculty of Agricultural and Environmental Sciences, McGill University, MontrealQC, Canada
- Department of Animal Science, Faculty of Agricultural and Environmental Sciences, McGill University, MontrealQC, Canada
| | - Franco Pagotto
- Bureau of Microbial Hazards, Food Directorate, Health Canada, OttawaON, Canada
- Listeriosis Reference Centre, Bureau of Microbial Hazards, Food Directorate, Health Canada, OttawaON, Canada
| | - Aleisha Reimer
- National Microbiology Laboratory, Public Health Agency of Canada, WinnipegMB, Canada
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Abrams AJ, Trees DL. Genomic sequencing of Neisseria gonorrhoeae to respond to the urgent threat of antimicrobial-resistant gonorrhea. Pathog Dis 2017; 75:3106325. [PMID: 28387837 PMCID: PMC6956991 DOI: 10.1093/femspd/ftx041] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 04/04/2017] [Indexed: 01/02/2023] Open
Abstract
The development of resistance of Neisseria gonorrhoeae to available first-line antibiotics, including penicillins, tetracyclines, fluoroquinolones and cephalosporins, has led to the circulation of multidrug-resistant gonorrhea at a global scale. Advancements in high-throughput whole-genome sequencing (WGS) provide useful tools that can be used to enhance gonococcal detection, treatment and management capabilities, which will ultimately aid in the control of antimicrobial resistant gonorrhea worldwide. In this minireview, we discuss the application of WGS of N. gonorrhoeae to strain typing, phylogenomic, molecular surveillance and transmission studies. We also examine the application of WGS analyses to the public health sector as well as the potential usage of WGS-based transcriptomic and epigenetic methods to identify novel gonococcal resistance mechanisms.
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Affiliation(s)
- A. Jeanine Abrams
- Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, GA 30333, USA
| | - David L. Trees
- Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, GA 30333, USA
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Kim Y, Park J, Kim M. Diagnostic approaches for inherited hemolytic anemia in the genetic era. Blood Res 2017; 52:84-94. [PMID: 28698843 PMCID: PMC5503903 DOI: 10.5045/br.2017.52.2.84] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 05/24/2017] [Accepted: 05/25/2017] [Indexed: 02/06/2023] Open
Abstract
Inherited hemolytic anemias (IHAs) are genetic diseases that present with anemia due to the increased destruction of circulating abnormal RBCs. The RBC abnormalities are classified into the three major disorders of membranopathies, hemoglobinopathies, and enzymopathies. Traditional diagnosis of IHA has been performed via a step-wise process combining clinical and laboratory findings. Nowadays, the etiology of IHA accounts for germline mutations of the responsible genes coding for the structural components of RBCs. Recent advances in molecular technologies, including next-generation sequencing, inspire us to apply these technologies as a first-line approach for the identification of potential mutations and to determine the novel causative genes in patients with IHAs. We herein review the concept and strategy for the genetic diagnosis of IHAs and provide an overview of the preparations for clinical applications of the new molecular technologies.
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Affiliation(s)
- Yonggoo Kim
- Department of Laboratory Medicine, Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Joonhong Park
- Department of Laboratory Medicine, Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Myungshin Kim
- Department of Laboratory Medicine, Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Goodwin S, McPherson JD, McCombie WR. Coming of age: ten years of next-generation sequencing technologies. Nat Rev Genet 2017; 17:333-51. [PMID: 27184599 PMCID: PMC10373632 DOI: 10.1038/nrg.2016.49] [Citation(s) in RCA: 2399] [Impact Index Per Article: 299.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Since the completion of the human genome project in 2003, extraordinary progress has been made in genome sequencing technologies, which has led to a decreased cost per megabase and an increase in the number and diversity of sequenced genomes. An astonishing complexity of genome architecture has been revealed, bringing these sequencing technologies to even greater advancements. Some approaches maximize the number of bases sequenced in the least amount of time, generating a wealth of data that can be used to understand increasingly complex phenotypes. Alternatively, other approaches now aim to sequence longer contiguous pieces of DNA, which are essential for resolving structurally complex regions. These and other strategies are providing researchers and clinicians a variety of tools to probe genomes in greater depth, leading to an enhanced understanding of how genome sequence variants underlie phenotype and disease.
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Affiliation(s)
- Sara Goodwin
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
| | - John D McPherson
- Department of Biochemistry and Molecular Medicine; and the Comprehensive Cancer Center, University of California, Davis, California 95817, USA
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Payne K, Eden M, Davison N, Bakker E. Toward health technology assessment of whole-genome sequencing diagnostic tests: challenges and solutions. Per Med 2017; 14:235-247. [PMID: 29767583 DOI: 10.2217/pme-2016-0089] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Whole-genome sequencing (WGS) is being applied within research settings across Europe to develop genomic WGS-based diagnostic tests. The focus of this perspective paper is to describe if, and how, current approaches of health technology assessment could be applied to WGS-based diagnostic tests. This perspective draws on the collective view from a trans-European multidisciplinary consortium of methodologists, clinicians and scientists. Specific challenges can be described by using the PICO (population, intervention, comparator, outcome) framework to inform health technology assessment. Practical solutions are suggested which require joined-up, multidisciplinary working across healthcare systems using existing expert networks so that emergent issues for the health technology assessment of WGS can be met in a timely fashion.
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Affiliation(s)
- Katherine Payne
- Manchester Centre for Health Economics, The University of Manchester, Manchester M13 9PL, UK
| | - Martin Eden
- Manchester Centre for Health Economics, The University of Manchester, Manchester M13 9PL, UK
| | - Niall Davison
- Manchester Centre for Health Economics, The University of Manchester, Manchester M13 9PL, UK
| | - Egbert Bakker
- Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
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Li X, Brock GN, Rouchka EC, Cooper NGF, Wu D, O’Toole TE, Gill RS, Eteleeb AM, O’Brien L, Rai SN. A comparison of per sample global scaling and per gene normalization methods for differential expression analysis of RNA-seq data. PLoS One 2017; 12:e0176185. [PMID: 28459823 PMCID: PMC5411036 DOI: 10.1371/journal.pone.0176185] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Accepted: 04/06/2017] [Indexed: 01/08/2023] Open
Abstract
Normalization is an essential step with considerable impact on high-throughput RNA sequencing (RNA-seq) data analysis. Although there are numerous methods for read count normalization, it remains a challenge to choose an optimal method due to multiple factors contributing to read count variability that affects the overall sensitivity and specificity. In order to properly determine the most appropriate normalization methods, it is critical to compare the performance and shortcomings of a representative set of normalization routines based on different dataset characteristics. Therefore, we set out to evaluate the performance of the commonly used methods (DESeq, TMM-edgeR, FPKM-CuffDiff, TC, Med UQ and FQ) and two new methods we propose: Med-pgQ2 and UQ-pgQ2 (per-gene normalization after per-sample median or upper-quartile global scaling). Our per-gene normalization approach allows for comparisons between conditions based on similar count levels. Using the benchmark Microarray Quality Control Project (MAQC) and simulated datasets, we performed differential gene expression analysis to evaluate these methods. When evaluating MAQC2 with two replicates, we observed that Med-pgQ2 and UQ-pgQ2 achieved a slightly higher area under the Receiver Operating Characteristic Curve (AUC), a specificity rate > 85%, the detection power > 92% and an actual false discovery rate (FDR) under 0.06 given the nominal FDR (≤0.05). Although the top commonly used methods (DESeq and TMM-edgeR) yield a higher power (>93%) for MAQC2 data, they trade off with a reduced specificity (<70%) and a slightly higher actual FDR than our proposed methods. In addition, the results from an analysis based on the qualitative characteristics of sample distribution for MAQC2 and human breast cancer datasets show that only our gene-wise normalization methods corrected data skewed towards lower read counts. However, when we evaluated MAQC3 with less variation in five replicates, all methods performed similarly. Thus, our proposed Med-pgQ2 and UQ-pgQ2 methods perform slightly better for differential gene analysis of RNA-seq data skewed towards lowly expressed read counts with high variation by improving specificity while maintaining a good detection power with a control of the nominal FDR level.
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Affiliation(s)
- Xiaohong Li
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, United States of America
- Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, United States of America
| | - Guy N. Brock
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, United States of America
- Department of Biomedical Informatics, Ohio State University, Columbus, OH, United States of America
| | - Eric C. Rouchka
- Department of Computer Engineering Computer Science, University of Louisville, Louisville, KY, United States of America
| | - Nigel G. F. Cooper
- Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, United States of America
| | - Dongfeng Wu
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, United States of America
| | - Timothy E. O’Toole
- Department of Cardiology, University of Louisville, Louisville, KY, United States of America
| | - Ryan S. Gill
- Department of Mathematics, University of Louisville, Louisville, KY, United States of America
| | - Abdallah M. Eteleeb
- Department of Internal Medicine, Oncology Division, Washington University, St. Louis, MO, United States of America
| | - Liz O’Brien
- Department of Epidemiology, University of Louisville, Louisville, KY, United States of America
| | - Shesh N. Rai
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, United States of America
- * E-mail:
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Elsensohn MH, Leblay N, Dimassi S, Campan-Fournier A, Labalme A, Roucher-Boulez F, Sanlaville D, Lesca G, Bardel C, Roy P. Statistical method to compare massive parallel sequencing pipelines. BMC Bioinformatics 2017; 18:139. [PMID: 28249565 PMCID: PMC5333416 DOI: 10.1186/s12859-017-1552-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2016] [Accepted: 02/16/2017] [Indexed: 02/01/2023] Open
Abstract
Background Today, sequencing is frequently carried out by Massive Parallel Sequencing (MPS) that cuts drastically sequencing time and expenses. Nevertheless, Sanger sequencing remains the main validation method to confirm the presence of variants. The analysis of MPS data involves the development of several bioinformatic tools, academic or commercial. We present here a statistical method to compare MPS pipelines and test it in a comparison between an academic (BWA-GATK) and a commercial pipeline (TMAP-NextGENe®), with and without reference to a gold standard (here, Sanger sequencing), on a panel of 41 genes in 43 epileptic patients. This method used the number of variants to fit log-linear models for pairwise agreements between pipelines. To assess the heterogeneity of the margins and the odds ratios of agreement, four log-linear models were used: a full model, a homogeneous-margin model, a model with single odds ratio for all patients, and a model with single intercept. Then a log-linear mixed model was fitted considering the biological variability as a random effect. Results Among the 390,339 base-pairs sequenced, TMAP-NextGENe® and BWA-GATK found, on average, 2253.49 and 1857.14 variants (single nucleotide variants and indels), respectively. Against the gold standard, the pipelines had similar sensitivities (63.47% vs. 63.42%) and close but significantly different specificities (99.57% vs. 99.65%; p < 0.001). Same-trend results were obtained when only single nucleotide variants were considered (99.98% specificity and 76.81% sensitivity for both pipelines). Conclusions The method allows thus pipeline comparison and selection. It is generalizable to all types of MPS data and all pipelines. Electronic supplementary material The online version of this article (doi:10.1186/s12859-017-1552-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- M H Elsensohn
- Service de Biostatistique-Bioinformatique, Hospices Civils de Lyon, 162 avenue Lacassagne, F-69003, Lyon, France. .,Université de Lyon, Lyon, France. .,Université Lyon 1, Villeurbanne, France. .,CNRS UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique Santé, Villeurbanne, France.
| | - N Leblay
- Service de Biostatistique-Bioinformatique, Hospices Civils de Lyon, 162 avenue Lacassagne, F-69003, Lyon, France.,Université de Lyon, Lyon, France.,Université Lyon 1, Villeurbanne, France.,CNRS UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique Santé, Villeurbanne, France
| | - S Dimassi
- Université de Lyon, Lyon, France.,Université Lyon 1, Villeurbanne, France.,Service de Génétique, Hospices Civils de Lyon, Lyon, France.,Centre de Recherche en Neurosciences de Lyon, CNRS UMR 5292, INSERM U1028, Lyon, France
| | - A Campan-Fournier
- Université de Lyon, Lyon, France.,Université Lyon 1, Villeurbanne, France.,Service de Génétique, Hospices Civils de Lyon, Lyon, France.,Centre de Recherche en Neurosciences de Lyon, CNRS UMR 5292, INSERM U1028, Lyon, France
| | - A Labalme
- Service de Génétique, Hospices Civils de Lyon, Lyon, France
| | - F Roucher-Boulez
- Université de Lyon, Lyon, France.,Université Lyon 1, Villeurbanne, France.,CNRS UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique Santé, Villeurbanne, France.,Service de Génétique, Hospices Civils de Lyon, Lyon, France
| | - D Sanlaville
- Université de Lyon, Lyon, France.,Université Lyon 1, Villeurbanne, France.,Service de Génétique, Hospices Civils de Lyon, Lyon, France.,Centre de Recherche en Neurosciences de Lyon, CNRS UMR 5292, INSERM U1028, Lyon, France
| | - G Lesca
- Université de Lyon, Lyon, France.,Université Lyon 1, Villeurbanne, France.,Service de Génétique, Hospices Civils de Lyon, Lyon, France.,Centre de Recherche en Neurosciences de Lyon, CNRS UMR 5292, INSERM U1028, Lyon, France
| | - C Bardel
- Service de Biostatistique-Bioinformatique, Hospices Civils de Lyon, 162 avenue Lacassagne, F-69003, Lyon, France.,Université de Lyon, Lyon, France.,Université Lyon 1, Villeurbanne, France.,CNRS UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique Santé, Villeurbanne, France
| | - P Roy
- Service de Biostatistique-Bioinformatique, Hospices Civils de Lyon, 162 avenue Lacassagne, F-69003, Lyon, France.,Université de Lyon, Lyon, France.,Université Lyon 1, Villeurbanne, France.,CNRS UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique Santé, Villeurbanne, France
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Kamps R, Brandão RD, Bosch BJVD, Paulussen ADC, Xanthoulea S, Blok MJ, Romano A. Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification. Int J Mol Sci 2017; 18:ijms18020308. [PMID: 28146134 PMCID: PMC5343844 DOI: 10.3390/ijms18020308] [Citation(s) in RCA: 315] [Impact Index Per Article: 39.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 01/19/2017] [Indexed: 12/17/2022] Open
Abstract
Next-generation sequencing (NGS) technology has expanded in the last decades with significant improvements in the reliability, sequencing chemistry, pipeline analyses, data interpretation and costs. Such advances make the use of NGS feasible in clinical practice today. This review describes the recent technological developments in NGS applied to the field of oncology. A number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA-sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequencing to identify risk modifiers and application for pre-implantation genetic diagnosis, cancer somatic mutation analysis, pharmacogenetics and liquid biopsy. Conclusive remarks, clinical limitations, implications and ethical considerations that relate to the different applications are provided.
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Affiliation(s)
- Rick Kamps
- Department of Clinical Genetics: GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, 6229HX Maastricht, The Netherlands.
| | - Rita D Brandão
- Department of Clinical Genetics: GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, 6229HX Maastricht, The Netherlands.
| | - Bianca J van den Bosch
- Department of Clinical Genetics: GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, 6229HX Maastricht, The Netherlands.
| | - Aimee D C Paulussen
- Department of Clinical Genetics: GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, 6229HX Maastricht, The Netherlands.
| | - Sofia Xanthoulea
- Department of Gynaecology and Obstetrics: GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, 6229HX Maastricht, The Netherlands.
| | - Marinus J Blok
- Department of Clinical Genetics: GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, 6229HX Maastricht, The Netherlands.
| | - Andrea Romano
- Department of Gynaecology and Obstetrics: GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, 6229HX Maastricht, The Netherlands.
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Zhang Q, Jun SR, Leuze M, Ussery D, Nookaew I. Viral Phylogenomics Using an Alignment-Free Method: A Three-Step Approach to Determine Optimal Length of k-mer. Sci Rep 2017; 7:40712. [PMID: 28102365 PMCID: PMC5244389 DOI: 10.1038/srep40712] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 12/08/2016] [Indexed: 11/25/2022] Open
Abstract
The development of rapid, economical genome sequencing has shed new light on the classification of viruses. As of October 2016, the National Center for Biotechnology Information (NCBI) database contained >2 million viral genome sequences and a reference set of ~4000 viral genome sequences that cover a wide range of known viral families. Whole-genome sequences can be used to improve viral classification and provide insight into the viral "tree of life". However, due to the lack of evolutionary conservation amongst diverse viruses, it is not feasible to build a viral tree of life using traditional phylogenetic methods based on conserved proteins. In this study, we used an alignment-free method that uses k-mers as genomic features for a large-scale comparison of complete viral genomes available in RefSeq. To determine the optimal feature length, k (an essential step in constructing a meaningful dendrogram), we designed a comprehensive strategy that combines three approaches: (1) cumulative relative entropy, (2) average number of common features among genomes, and (3) the Shannon diversity index. This strategy was used to determine k for all 3,905 complete viral genomes in RefSeq. The resulting dendrogram shows consistency with the viral taxonomy of the ICTV and the Baltimore classification of viruses.
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Affiliation(s)
- Qian Zhang
- UT-ORNL Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, TN 37996, USA
- Comparative Genomics Group, Biosciences Division, Oak Ridge National Laboratory Oak Ridge, TN 37831 USA
| | - Se-Ran Jun
- Comparative Genomics Group, Biosciences Division, Oak Ridge National Laboratory Oak Ridge, TN 37831 USA
- Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Michael Leuze
- Joint Institute for Computational Sciences, University of Tennessee, Knoxville, TN 37831, USA
- Computational Biomolecular Modeling and Bioinformatics Group, Computer Science and Mathematics Division, Oak Ridge National Laboratories, Oak Ridge, TN 37831, USA
| | - David Ussery
- Comparative Genomics Group, Biosciences Division, Oak Ridge National Laboratory Oak Ridge, TN 37831 USA
- Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Intawat Nookaew
- Comparative Genomics Group, Biosciences Division, Oak Ridge National Laboratory Oak Ridge, TN 37831 USA
- Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
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Pirih N, Kunej T. Toward a Taxonomy for Multi-Omics Science? Terminology Development for Whole Genome Study Approaches by Omics Technology and Hierarchy. ACTA ACUST UNITED AC 2017; 21:1-16. [DOI: 10.1089/omi.2016.0144] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Affiliation(s)
- Nina Pirih
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domzale, Slovenia
| | - Tanja Kunej
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domzale, Slovenia
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Avramouli A, Vlamos PM. Integrating Omic Technologies in Alzheimer's Disease. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 987:177-184. [PMID: 28971457 DOI: 10.1007/978-3-319-57379-3_16] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Scientific advances in biomedical disciplines have allowed us to identify the underlying causes of many diseases with increased comprehension-leading the way towards precision medicine. In this context, unique disease and medical traits pave the way for the development of adapted disease management, drugs and therapies tailored to each patient. Bearing in mind that reductionism, an approach that has dominated biomedical research for many years and has resulted in the identification of definite cellular phenotypes and human diseases which are linked with specific integral molecules, we strongly believe that Alzheimer's Disease, one of the most common neurodegenerative diseases, could not be applied to the model of one disease-one assay-one drug. Regarding the discrete complexities in the molecular pathogenesis combined with the limited knowledge of inherited and sporadic forms of Alzheimer's disease, the great heterogeneity in the clinical development, as well as the plethora of validated biomarkers that have been proposed for early diagnosis or prognosis of the disease, we presume that a radically different way of thinking is in demand for comprehensive explanations of the molecular pathogenesis of the disease. In this article we highlight the most recent advances made in the omics field of systems biology towards a more complete understanding of Alzheimer's disease mechanisms, emphasizing to the paramount emergence of the development of various high-throughput strategies applied to the omics sciences.
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Niemiec E, Borry P, Pinxten W, Howard HC. Content Analysis of Informed Consent for Whole Genome Sequencing Offered by Direct-to-Consumer Genetic Testing Companies. Hum Mutat 2016; 37:1248-1256. [PMID: 27647801 DOI: 10.1002/humu.23122] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2016] [Accepted: 09/16/2016] [Indexed: 02/05/2023]
Abstract
Whole exome sequencing (WES) and whole genome sequencing (WGS) have become increasingly available in the research and clinical settings and are now also being offered by direct-to-consumer (DTC) genetic testing (GT) companies. This offer can be perceived as amplifying the already identified concerns regarding adequacy of informed consent (IC) for both WES/WGS and the DTC GT context. We performed a qualitative content analysis of Websites of four companies offering WES/WGS DTC regarding the following elements of IC: pre-test counseling, benefits and risks, and incidental findings (IFs). The analysis revealed concerns, including the potential lack of pre-test counseling in three of the companies studied, missing relevant information in the risks and benefits sections, and potentially misleading information for consumers. Regarding IFs, only one company, which provides opportunistic screening, provides basic information about their management. In conclusion, some of the information (and related practices) present on the companies' Web pages salient to the consent process are not adequate in reference to recommendations for IC for WGS or WES in the clinical context. Requisite resources should be allocated to ensure that commercial companies are offering high-throughput sequencing under responsible conditions, including an adequate consent process.
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Affiliation(s)
- Emilia Niemiec
- Erasmus Plus Doctoral Programme in Law, Science and Technology, CIRSFID, University of Bologna, Bologna, Italy.,Department of Law, University of Turin, Turin, Italy.,Centre for Ethics and Law in the Life Sciences, Leibniz University Hannover, Hannover, Germany
| | - Pascal Borry
- Centre for Biomedical Ethics and Law, Department of Public Health and Primary Care KU Leuven, Leuven, Belgium
| | - Wim Pinxten
- Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
| | - Heidi Carmen Howard
- Centre for Research Ethics and Bioethics, Uppsala University, Uppsala, Sweden
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Aguilar H, Sanchez E, Braña I, Vivancos A, Rodon J. Molecular screening programmes for precision medicine: lessons learned from personalized medicine trials. EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT 2016. [DOI: 10.1080/23808993.2016.1238285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Li M, Diamandis EP. Technology-driven diagnostics: From smart doctor to smartphone. Crit Rev Clin Lab Sci 2016; 53:268-76. [DOI: 10.3109/10408363.2016.1149689] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Michelle Li
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada,
| | - Eleftherios P. Diamandis
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada,
- Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada, and
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
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Malentacchi F, Mancini I, Brandslund I, Vermeersch P, Schwab M, Marc J, van Schaik RHN, Siest G, Theodorsson E, Pazzagli M, Di Resta C. Is laboratory medicine ready for the era of personalized medicine? A survey addressed to laboratory directors of hospitals/academic schools of medicine in Europe. Clin Chem Lab Med 2016; 53:981-8. [PMID: 25995323 DOI: 10.1515/cclm-2015-0171] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 03/23/2015] [Indexed: 11/15/2022]
Abstract
Developments in "-omics" are creating a paradigm shift in laboratory medicine leading to personalized medicine. This allows the increase in diagnostics and therapeutics focused on individuals rather than populations. In order to investigate whether laboratory medicine is ready to play a key role in the integration of personalized medicine in routine health care and set the state-of-the-art knowledge about personalized medicine and laboratory medicine in Europe, a questionnaire was constructed under the auspices of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) and the European Society of Pharmacogenomics and Personalised Therapy (ESPT). The answers of the participating laboratory medicine professionals indicate that they are aware that personalized medicine can represent a new and promising health model, and that laboratory medicine should play a key role in supporting the implementation of personalized medicine in the clinical setting. Participants think that the current organization of laboratory medicine needs additional/relevant implementations such as (i) new technological facilities in -omics; (ii) additional training for the current personnel focused on the new methodologies; (iii) incorporation in the laboratory of new competencies in data interpretation and counseling; and (iv) cooperation and collaboration among professionals of different disciplines to integrate information according to a personalized medicine approach.
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