MCB Seminar | Low-Coverage Whole Genome Sequencing of cell free DNA: Less Is More, Sept. 14

Tuesday, September 14, 2021 4:35pm to 5:55pm

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MCB Seminar | Low-Coverage Whole Genome Sequencing of cell free DNA: Less Is More, Sept. 14

The Molecular and Cellular Biology Seminar series features Prateek Kulkarni discussing "Low-Coverage Whole Genome Sequencing of cell free DNA: Less Is More" on Sept. 14 from 4:35 to 5:55 p.m.

 

Kulkarni is a graduate student in the Biological Sciences and Molecular Cellular Biology programs.

 

Abstract: From gender reveals in first trimester to monitoring of cancer in chemotherapy, liquid biopsies have garnered attention in recent times. Extracellular cell-free DNA (cfDNA) from body fluids is one of the prime components that have been rapidly integrated into the pipeline for such analyses. The cfDNA is released from cells via apoptotic/necrotic processes or secreted through extracellular vesicles. The cfDNA can give crucial insights into genetic variants such as downs syndrome with a high accuracy in pregnancies with high risk [1] or monitoring unresectable tumors [2]. Next-generation sequencing has become a go-to technology to process and analyze DNA/RNA samples. The whole genome sequencing (WGS) technology has improved with regards to cost, time, and efficiency tremendously in recent years. Indeed, the average sequencing read depth of about 80x to as high as 450x is used in high-throughput WGS. However, the new in silico revolution of skimming the sample to as low as 0.1x, termed as low-coverage whole genome sequencing (LC-WGS) has shown surprising promise. In addition to being 10 times more affordable than WGS, LC-WGS is also superior to microarrays as it bypasses the requirement of pre-defined single nucleotide polymorphisms and copy number variants. Software tools like GLIMPSE, BEAGLE, and STITCH have been developed to supplement low-coverage analysis [3]. LC-WGS capitalizes on its property of not being dependent on reference panels, making genetic association studies feasible as reported in a study of fetal cfDNA in Chinese women population [4]. Furthermore, mutational variation in cfDNA has been successfully performed by 2.2x coverage LC-WGS to identify malignant nerve sheath tumor from its benign form which is otherwise traditionally challenging due to high tumor heterogeneity [5]. Overall, LC-WGS of cfDNA provides more cost-efficient, time-dependent monitoring, and accurate analysis of variants among cell populations.

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