NGS - Module 3


Module 3: NGS - Clinical Applications and Implications

OBJECTIVE: Acquire knowledge of disease association studies, cancer genomics, personalized medicine, and clinical implications of NGS.

Videos and Slides References and Resources

NGS - Clinical Applications and Implications I

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NGS - Clinical Applications and Implications II

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NGS - Clinical Applications and Implications III

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Guest Lecture: Mark Boguski, PhD

Whole Genome Analysis as a Universal Diagnostic - A Pathologist’s Perspective

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Guest Lecture: George M. Church, PhD
Next Gen Sequencing - Applications & Implications

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Tools and databases useful for investigating associations between genetic variation and human disease:
  1. Savas S. Useful genetic variation databases for oncologists investigating the genetic basis of variable treatment response and survival in cancer. Acta Oncol. 2010 Nov;49(8):1217-26.
  2. Wall DP et al. Genotator: a disease-agnostic tool for genetic annotation of disease. BMC Med Genomics. 2010 Oct 29;3:50.

Clinical sequencing publications:

  1. Ashley EA et al. Clinical assessment incorporating a personal genome. Lancet. 2010 May 1;375(9725):1525-35.
  2. Jones SJ et al. Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors. Genome Biol. 2010;11(8):R82.
  3. Link DC et al. Identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML. JAMA. 2011 Apr 20;305(15):1568-76.
  4. Welch JS et al. Use of whole-genome sequencing to diagnose a cryptic fusion oncogene. JAMA. 2011 Apr 20;305(15):1577-84.
  5. Lupski JR et al. Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N Engl J Med. 2010 Apr 1;362(13):1181-91.
  6. Worthey EA et al. Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med. 2011 Mar;13(3):255-62.

The promise of personalized medicine:

  1. Ellsworth RE et al. Breast cancer in the personal genomics era. Curr Genomics. 2010 May;11(3):146-61
  2. Diamandis M et al. Personalized medicine: marking a new epoch in cancer patient management. Mol Cancer Res. 2010 Sep;8(9):1175-87.
  3. Boguski MS et al. Customized care 2020: how medical sequencing and network biology will enable personalized medicine. F1000 Biol Rep. 2009 Sep 28;1. pii: 73.


Review, identify, examine and then report on a clinically actionable set of information or metric based on one or more genetic variants.  Study and identify the original discovery of the variant(s) and review the original scientific hypothesis relating the variant to the disease or symptom.  Trace the progress of the discovery and translation of the variant(s) from discovery, to association with the disease status, to validation, to incorporation into clinical tool or device, to validation of the device or tool, to current status (widespread or even rare use) in healthcare.  In short, record the narrative from bench to bedside.  Review the literature relevant to the background, science, validation and current clinical use. Include a discussion of the key data sources used to develop the clinical use of the variant(s). Discuss the use of NGS technology, data, algorithms, methods and analysis in the narrative.  If NGS was not used, project how NGS technology could be used to replicate the findings, or in place of the technologies that were used, to discover and validate new clinically relevant variants.  Write a "translational" statement (minimum ten pages) on the question, background, data collection design and methods relevant to the development from discovery to use.