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Diagnostic genomics

Guest editors: James Lupski and Joris Veltman

Whole genome and exome sequencing are now being implemented in the clinic. Leading hospitals around the world have undertaken thousands of sequencing tests on patients, and recent reports have demonstrated a diagnostic success rate of around 25%, with higher rates for certain disorders. To mark this important move into the clinic, Genome Medicine is pleased to announce a special issue on Diagnostic Genomics from guest editors Joris Veltman, from Radboud University Medical Centre, and Jim Lupski, from Baylor College of Medicine.

This collection of articles has not been sponsored and articles have undergone the journal’s standard peer-review process.

  1. Method

    A 26-hour system of highly sensitive whole genome sequencing for emergency management of genetic diseases

    While the cost of whole genome sequencing (WGS) is approaching the realm of routine medical tests, it remains too tardy to help guide the management of many acute medical conditions. Rapid WGS is imperative in...

    Neil A. Miller, Emily G. Farrow, Margaret Gibson, Laurel K. Willig, Greyson Twist, Byunggil Yoo, Tyler Marrs, Shane Corder, Lisa Krivohlavek, Adam Walter, Josh E. Petrikin, Carol J. Saunders, Isabelle Thiffault, Sarah E. Soden, Laurie D. Smith, Darrell L. Dinwiddie…

    Genome Medicine 2015 7:100

    Published on: 30 September 2015

  2. Method

    Rapid metagenomic identification of viral pathogens in clinical samples by real-time nanopore sequencing analysis

    We report unbiased metagenomic detection of chikungunya virus (CHIKV), Ebola virus (EBOV), and hepatitis C virus (HCV) from four human blood samples by MinION nanopore sequencing coupled to a newly developed, ...

    Alexander L. Greninger, Samia N. Naccache, Scot Federman, Guixia Yu, Placide Mbala, Vanessa Bres, Doug Stryke, Jerome Bouquet, Sneha Somasekar, Jeffrey M. Linnen, Roger Dodd, Prime Mulembakani, Bradley S. Schneider, Jean-Jacques Muyembe-Tamfum, Susan L. Stramer and Charles Y. Chiu

    Genome Medicine 2015 7:99

    Published on: 29 September 2015

  3. Research

    An assessment of sex bias in neurodevelopmental disorders

    Neurodevelopmental disorders such as autism and intellectual disability have a sex bias skewed towards boys; however, systematic assessment of this bias is complicated by the presence of significant genetic an...

    Andrew Polyak, Jill A. Rosenfeld and Santhosh Girirajan

    Genome Medicine 2015 7:94

    Published on: 27 August 2015

  4. Opinion

    So rare we need to hunt for them: reframing the ethical debate on incidental findings

    Incidental findings are the subject of intense ethical debate in medical genomic research. Every human genome contains a number of potentially disease-causing alterations that may be detected during comprehens...

    Sebastian Schuol, Christoph Schickhardt, Stefan Wiemann, Claus R. Bartram, Klaus Tanner, Roland Eils, Benjamin Meder, Daniela Richter, Hanno Glimm, Christof von Kalle and Eva C. Winkler

    Genome Medicine 2015 7:83

    Published on: 30 July 2015

  5. Review

    Next-generation sequencing to guide cancer therapy

    As a result of multiple technological and practical advances, high-throughput sequencing, known more commonly as “next-generation” sequencing (NGS), can now be incorporated into standard clinical practice. Whe...

    Jeffrey Gagan and Eliezer M. Van Allen

    Genome Medicine 2015 7:80

    Published on: 29 July 2015

  6. Software

    ClinLabGeneticist: a tool for clinical management of genetic variants from whole exome sequencing in clinical genetic laboratories

    Routine clinical application of whole exome sequencing remains challenging due to difficulties in variant interpretation, large dataset management, and workflow integration. We describe a tool named ClinLabGen...

    Jinlian Wang, Jun Liao, Jinglan Zhang, Wei-Yi Cheng, Jörg Hakenberg, Meng Ma, Bryn D. Webb, Rajasekar Ramasamudram-chakravarthi, Lisa Karger, Lakshmi Mehta, Ruth Kornreich, George A. Diaz, Shuyu Li, Lisa Edelmann and Rong Chen

    Genome Medicine 2015 7:77

    Published on: 29 July 2015

  7. Comment

    Global genetic carrier testing: a vision for the future

    Expanded genetic carrier testing is changing clinical practice. Current experience highlights the need for rigorous curation of tens of thousands of variants as to their pathogenicity and phenotypic effects. T...

    Arthur L. Beaudet

    Genome Medicine 2015 7:79

    Published on: 29 July 2015

  8. Editorial

    From genes to genomes in the clinic

    Next-generation sequencing is revolutionizing medical genetics and in the near future will pervade all medical fields. To maximize the potential clinical utility of this approach, global data sharing and pheno...

    Joris A. Veltman and James R. Lupski

    Genome Medicine 2015 7:78

    Published on: 29 July 2015

  9. Method

    CSN and CAVA: variant annotation tools for rapid, robust next-generation sequencing analysis in the clinical setting

    Next-generation sequencing (NGS) offers unprecedented opportunities to expand clinical genomics. It also presents challenges with respect to integration with data from other sequencing methods and historical d...

    Márton Münz, Elise Ruark, Anthony Renwick, Emma Ramsay, Matthew Clarke, Shazia Mahamdallie, Victoria Cloke, Sheila Seal, Ann Strydom, Gerton Lunter and Nazneen Rahman

    Genome Medicine 2015 7:76

    Published on: 28 July 2015

  10. Method

    ENVE: a novel computational framework characterizes copy-number mutational landscapes in colorectal cancers from African American patients

    Reliable detection of somatic copy-number alterations (sCNAs) in tumors using whole-exome sequencing (WES) remains challenging owing to technical (inherent noise) and sample-associated variability in WES data....

    Vinay Varadan, Salendra Singh, Arman Nosrati, Lakshmeswari Ravi, James Lutterbaugh, Jill S. Barnholtz-Sloan, Sanford D. Markowitz, Joseph E. Willis and Kishore Guda

    Genome Medicine 2015 7:69

    Published on: 20 July 2015

  11. Research

    Genomic prediction of celiac disease targeting HLA-positive individuals

    Genomic prediction aims to leverage genome-wide genetic data towards better disease diagnostics and risk scores. We have previously published a genomic risk score (GRS) for celiac disease (CD), a common and hi...

    Gad Abraham, Alexia Rohmer, Jason A. Tye-Din and Michael Inouye

    Genome Medicine 2015 7:72

    Published on: 16 July 2015

  12. Research

    Achieving high-sensitivity for clinical applications using augmented exome sequencing

    Whole exome sequencing is increasingly used for the clinical evaluation of genetic disease, yet the variation of coverage and sensitivity over medically relevant parts of the genome remains poorly understood. ...

    Anil Patwardhan, Jason Harris, Nan Leng, Gabor Bartha, Deanna M. Church, Shujun Luo, Christian Haudenschild, Mark Pratt, Justin Zook, Marc Salit, Jeanie Tirch, Massimo Morra, Stephen Chervitz, Ming Li, Michael Clark, Sarah Garcia…

    Genome Medicine 2015 7:71

    Published on: 16 July 2015

  13. Software

    Cpipe: a shared variant detection pipeline designed for diagnostic settings

    The benefits of implementing high throughput sequencing in the clinic are quickly becoming apparent. However, few freely available bioinformatics pipelines have been built from the ground up with clinical geno...

    Simon P. Sadedin, Harriet Dashnow, Paul A. James, Melanie Bahlo, Denis C. Bauer, Andrew Lonie, Sebastian Lunke, Ivan Macciocca, Jason P. Ross, Kirby R. Siemering, Zornitza Stark, Susan M. White, Graham Taylor, Clara Gaff, Alicia Oshlack and Natalie P. Thorne

    Genome Medicine 2015 7:68

    Published on: 10 July 2015

  14. Research

    Prospective participant selection and ranking to maximize actionable pharmacogenetic variants and discovery in the eMERGE Network

    In an effort to return actionable results from variant data to electronic health records (EHRs), participants in the Electronic Medical Records and Genomics (eMERGE) Network are being sequenced with the target...

    David R. Crosslin, Peggy D. Robertson, David S. Carrell, Adam S. Gordon, David S. Hanna, Amber Burt, Stephanie M. Fullerton, Aaron Scrol, James Ralston, Kathleen Leppig, Andrea Hartzler, Eric Baldwin, Mariza de Andrade, Iftikhar J. Kullo, Gerard Tromp, Kimberly F. Doheny…

    Genome Medicine 2015 7:67

    Published on: 3 July 2015

  15. Research

    BALL-SNP: combining genetic and structural information to identify candidate non-synonymous single nucleotide polymorphisms

    High-throughput genetic testing is increasingly applied in clinics. Next-Generation Sequencing (NGS) data analysis however still remains a great challenge. The interpretation of pathogenicity of single variant...

    Sabine C. Mueller, Christina Backes, Olga V. Kalinina, Benjamin Meder, Daniel Stöckel, Hans-Peter Lenhof, Eckart Meese and Andreas Keller

    Genome Medicine 2015 7:65

    Published on: 1 July 2015

  16. Research

    Secondary findings and carrier test frequencies in a large multiethnic sample

    Besides its growing importance in clinical diagnostics and understanding the genetic basis of Mendelian and complex diseases, whole exome sequencing (WES) is a rich source of additional information of potentia...

    Tomasz Gambin, Shalini N. Jhangiani, Jennifer E. Below, Ian M. Campbell, Wojciech Wiszniewski, Donna M. Muzny, Jeffrey Staples, Alanna C. Morrison, Matthew N. Bainbridge, Samantha Penney, Amy L. McGuire, Richard A. Gibbs, James R. Lupski and Eric Boerwinkle

    Genome Medicine 2015 7:54

    Published on: 13 June 2015