An integrated framework for reporting clinically relevant biomarkers from paired tumor/normal genomic and transcriptomic sequencing data in support of clinical trials in personalized medicine

Sara Nasser, Ahmet A. Kurdolgu, Tyler Izatt, Jessica Aldrich, Megan L. Russell, Alexis Christoforides, Wiabhav Tembe, Jeffery A. Keifer, Jason J. Corneveaux, Sara A. Byron, Karen M. Forman, Clarice Zuccaro, Jonathan J. Keats, Patricia M. Lorusso, John D. Carpten, Jeffrey M. Trent, David W. Craig

Research output: Chapter in Book/Report/Conference proceedingConference contribution


The ability to rapidly sequence the tumor and germline DNA of an individual holds the eventual promise of revolutionizing our ability to match targeted therapies to tumors harboring the associated genetic biomarkers. Analyzing high throughput genomic data consisting of millions of base pairs and discovering alterations in clinically actionable genes in a structured and real time manner is at the crux of personalized testing. This requires a computational architecture that can monitor and track a system within a regulated environment as terabytes of data are reduced to a small number of therapeutically relevant variants, delivered as a diagnostic laboratory developed test. These high complexity assays require data structures that enable real-time and retrospective ad-hoc analysis, with a capability of updating to keep up with the rapidly changing genomic and therapeutic options, all under a regulated environment that is relevant under both CMS and FDA depending on application.We describe a exible computational framework that uses a paired tumor/normal sample allowing for complete analysis and reporting in approximately 24 hours, providing identification of single nucleotide changes, small insertions and deletions, chromosomal rearrangements, gene fusions and gene expression with positive predictive values over 90%. In this paper we present the challenges in integrating clinical, genomic and annotation databases to provide interpreted draft reports which we utilize within ongoing clinical research protocols. We demonstrate the need to retire from existing performance measurements of accuracy and specificity and measure metrics that are meaningful to a genomic diagnostic environment. This paper presents a three-tier infrastructure that is currently being used to analyze an individual genome and provide available therapeutic options via a clinical report. Our framework utilizes a non-relational variant-centric database that is scaleable to a large amount of data and addresses the challenges and limitations of a relational database system. Our system is continuously monitored via multiple trackers each catering differently to the diversity of users involved in this process. These trackers designed in analytics web-app framework provide status updates for an individual sample accurate to a few minutes. In this paper, we also present our outcome delivery process that is designed and delivered adhering to the standards defined by various regulation agencies involved in clinical genomic testing.

Original languageEnglish (US)
Title of host publication20th Pacific Symposium on Biocomputing, PSB 2015
PublisherStanford University
Number of pages12
StatePublished - 2015
Externally publishedYes
Event20th Pacific Symposium on Biocomputing, PSB 2015 - Big Island, United States
Duration: Jan 4 2015Jan 8 2015


Other20th Pacific Symposium on Biocomputing, PSB 2015
Country/TerritoryUnited States
CityBig Island


  • Genomic Testing
  • Next-Gen Sequencing Analysis
  • Personalized Medicine

ASJC Scopus subject areas

  • Computational Theory and Mathematics
  • Biomedical Engineering


Dive into the research topics of 'An integrated framework for reporting clinically relevant biomarkers from paired tumor/normal genomic and transcriptomic sequencing data in support of clinical trials in personalized medicine'. Together they form a unique fingerprint.

Cite this