Journal:Bioinformatics workflow for clinical whole genome sequencing at Partners HealthCare Personalized Medicine
| Full article title | Bioinformatics workflow for clinical whole genome sequencing at Partners HealthCare Personalized Medicine |
|---|---|
| Journal | Journal of Personalized Medicine |
| Author(s) | Tsai, E.A.; Shakbatyan, R.; Evan, J.; Rossetti, P.; Graham, C.; Sharma, H.; Lin, C.-F., Lebo, M.S. |
| Author affiliation(s) | Partners HealthCare, Brigham and Women’s Hospital, Harvard Medical School |
| Primary contact | Tel.: +1-617-768-8292 |
| Editors | Weiss, S.T.; Liggett, S.B. |
| Year published | 2016 |
| Volume and issue | 6(1) |
| Page(s) | 12 |
| DOI | 10.3390/jpm6010012 |
| ISSN | 2075-4426 |
| Distribution license | Creative Commons Attribution 4.0 International |
| Website | http://www.mdpi.com/2075-4426/6/1/12/htm |
| Download | http://www.mdpi.com/2075-4426/6/1/12/pdf (PDF) |
 |
This article should not be considered complete until this message box has been removed. This is a work in progress. |
Abstract
Effective implementation of precision medicine will be enhanced by a thorough understanding of each patient’s genetic composition to better treat his or her presenting symptoms or mitigate the onset of disease. This ideally includes the sequence information of a complete genome for each individual. At Partners HealthCare Personalized Medicine, we have developed a clinical process for whole genome sequencing (WGS) with application in both healthy individuals and those with disease. In this manuscript, we will describe our bioinformatics strategy to efficiently process and deliver genomic data to geneticists for clinical interpretation. We describe the handling of data from FASTQ to the final variant list for clinical review for the final report. We will also discuss our methodology for validating this workflow and the cost implications of running WGS.
Keywords: clinical sequencing, WGS, NGS, next generation sequencing, bioinformatics, validation, precision medicine
Introduction
Precision medicine is becoming an increasing focus in medical research.[1] To achieve the resolution necessary to personalize clinical care, greater attention has been drawn towards higher resolution of the patient genome. Next generation sequencing (NGS) provided a cost-effective method for targeted sequencing of known disease genes at base pair resolution.[2] Moreover, the advent of exome sequencing enabled rapid discovery of genes causing Mendelian disorders. While gene panels and exome sequencing have proved fast and cost-effective for delivering genomic results back to the patient, these technologies are limited by our current knowledge of the exome, which changes over time. Additionally, the use of targeted capture may introduce biases to the data, including PCR duplicates, depth of coverage disparities, and failures at difficult to amplify target regions.[3]
References
- ↑ Collins, F.S.; Varmus, H. (2015). "A new initiative on precision medicine". New England Journal of Medicine 372 (9): 793–5. doi:10.1056/NEJMp1500523. PMID 25635347.
- ↑ Alfares, A.A.; Kelly, M.A.; McDermott, G. et al. (2015). "Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: Expanded panels offer limited additional sensitivity". Genetics in Medicine 17 (11): 880–8. doi:10.1038/gim.2014.205. PMID 25611685.
- ↑ Harismendy, O.; Ng, P.C.; Strausberg, R.L. et al. (2009). "Evaluation of next generation sequencing platforms for population targeted sequencing studies". Genome Biology 10 (3): R32. doi:10.1186/gb-2009-10-3-r32. PMC PMC2691003. PMID 19327155. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2691003.
Notes
This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added.
