Dr. Sachet Shukla's Talk

Oct 19, 2015 - 17:00

Oct 19, 2015 - 18:00

Room # 118 Chem. Engg. Dept.

Seminars

Dr. Sachet Shukla Senior Scientist at Dana-Farber Cancer Institute.

Abstract: Detection of somatic mutations in human leukocyte antigen (HLA) genes using whole-exome sequencing (WES) is hampered by the high polymorphism of the HLA loci which prevents alignment of sequencing reads to the human reference genome. We describe a computational pipeline that enables accurate inference of germline alleles of class I HLA-A B and C genes and subsequent detection of mutations in these genes using the inferred alleles as a reference. Analysis of WES data from 7 930 pairs of tumor and healthy tissue from the same patient revealed 298 nonsilent HLA mutations in tumors from 266 patients. These 298 mutations are enriched for likely functional mutations including putative loss-of-function events. Recurrence of mutations suggested that these 'hotspot' sites were positively selected. Cancers with recurrent somatic HLA mutations were associated with upregulation of signatures of cytolytic activity characteristic of tumor infiltration by effector lymphocytes supporting immune evasion by altered HLA function as a contributory mechanism in cancer.Biography: Dr. Sachet Shukla is a Senior Scientist at Dana-Farber Cancer Institute and an Associated Scientist at the Broad Institute. His primary area of work is cancer genomics with a special focus on immunology. He has developed computational algorithms that are being used by several research groups globally and have featured in high-impact publications. He is currently in-charge of bioinformatic data analysis from two ongoing clinical trials at Dana-Farber. He was previously the lead computational biologist at NewLink Genetics an immunotherapeutic start-up which has since gone public (NASDAQ: NLNK). Sachet has a Bachelor's degree in Chemical Engineering from Indian Institute of Technology - Kharagpur and a dual major Ph.D. in Bioinformatics and Statistics from Iowa State University. All are invited for the seminar in Chemical Engineering Department. Mandatory for CL702/704.