Home
Seminar Series:Patrick Flaherty, PhD (WPI) "Detecting Rare Single-Nucleotide Variants"
Science / Technology - Lecture/Discussion - WPI Only
Wednesday, September 12, 2012
4:00 PM-5:00 PM
Gateway Park
GP-1002
DEPARTMENT OF BIOMEDICAL ENGINEERING
SEMINAR SERIES
Wednesday, September 12, 2012
4:00-5:00 PM
Gateway Park, Room 1002
“Detecting Rare Single-Nucleotide Variants”
With next-generation DNA sequencing technologies, one can interrogate a specific genomic region of interest at very high depth of coverage and identify less prevalent, rare mutations in heterogeneous clinical samples.
However, the mutation detection levels are limited by the error rate of the sequencing technology as well as by the availability of variant-calling algorithms with high statistical power and low false positive rates. We demonstrate that we can robustly detect mutations at 0.1% fractional representation. To achieve this sensitive level of mutation detection, we integrate a high accuracy indexing strategy and reference replication for estimating sequencing error variance. As a clinical application of this method, we analyzed nine clinical samples of
H1N1 influenza A and detected an oseltamivir (antiviral therapy) resistance mutation in the H1N1 neuraminidase gene at a sample fraction of 0.18%. As a next step, we are using the approach to identify point mutations associated with multiple sclerosis by pooling hundreds of samples and using deep-sequencing to identify variants that are exclusive to affected individuals.
Patrick Flaherty, PhD
Assistant Professor
Biomedical Engineering Department
Worcester Polytechnic Institute
Suggested Audiences:
College
E-mail:
bme-web@wpi.edu
Last Modified: August 30, 2012 at 3:55 PM
Powered by the Social Web - Bringing people together through Events, Places, & Common Interests
Seminar Series:Patrick Flaherty, PhD (WPI) "Detecting Rare Single-Nucleotide Variants"
Science / Technology - Lecture/Discussion - WPI Only
Wednesday, September 12, 2012
4:00 PM-5:00 PM
Gateway Park
GP-1002
DEPARTMENT OF BIOMEDICAL ENGINEERING
SEMINAR SERIES
Wednesday, September 12, 2012
4:00-5:00 PM
Gateway Park, Room 1002
“Detecting Rare Single-Nucleotide Variants”
With next-generation DNA sequencing technologies, one can interrogate a specific genomic region of interest at very high depth of coverage and identify less prevalent, rare mutations in heterogeneous clinical samples.
However, the mutation detection levels are limited by the error rate of the sequencing technology as well as by the availability of variant-calling algorithms with high statistical power and low false positive rates. We demonstrate that we can robustly detect mutations at 0.1% fractional representation. To achieve this sensitive level of mutation detection, we integrate a high accuracy indexing strategy and reference replication for estimating sequencing error variance. As a clinical application of this method, we analyzed nine clinical samples of
H1N1 influenza A and detected an oseltamivir (antiviral therapy) resistance mutation in the H1N1 neuraminidase gene at a sample fraction of 0.18%. As a next step, we are using the approach to identify point mutations associated with multiple sclerosis by pooling hundreds of samples and using deep-sequencing to identify variants that are exclusive to affected individuals.
Patrick Flaherty, PhD
Assistant Professor
Biomedical Engineering Department
Worcester Polytechnic Institute
Suggested Audiences: College
E-mail: bme-web@wpi.edu
Last Modified: August 30, 2012 at 3:55 PM
Powered by the Social Web - Bringing people together through Events, Places, & Common Interests