Matthew Leventhal, PhD

The X and Y chromosomes play a crucial role in human sex determination. Females have two copies of the X chromosome, while males have one X chromosome and one Y chromosome. In females, the second copy of the X chromosome is silenced early in development, meaning that only one of the X chromosomes is expressed. As a result, mutations on the activated X chromosome are more likely to change cellular functions and in context of cancer, could lead to more rapid disease progression. Dr. Leventhal proposes a novel computational approach to distinguish between the actively expressed and silenced X chromosomes in females. He hopes to use this method to analyze a dataset of over 8,000 tumors to identify potential new drivers and molecular vulnerabilities within 31 types of cancer. He will model whether these alterations can occur in pre-cancerous cells, indicating that they could be targets for early therapeutic intervention.

Dr. Leventhal will develop a computational tool that models the error rate of statistical phasing in bulk whole-genome sequencing and corrects these errors to determine accurate haplotype-specific copy number of all chromosomes. This model integrates genomics with RNA-seq data to determine the active and inactive X chromosome. The subsequent error correction will allow him to perform the first pan-cancer analysis in over 8546 tumors to identify recurrent copy number alterations affecting the active or inactive X chromosome.