Quantitative Issues in Cancer Research Working Seminar
October 18 @ 1:00 pm - 1:50 pm
Martin Hemberg, Ph.D.
Assistant Professor of Neurology, Brigham & Women’s Hospital / Harvard Medical School
“Searching for Alien DNA: Leveraging sequences missing from the human genome to diagnose cancer”
ABSTRACT: In this talk, I will first describe our characterization of nullomers, short (11-18 nts) DNA sequences that are absent from a genome. We identify all possible nullomers and nullpeptides in the genomes and proteomes of thirty eukaryotes and demonstrate that a significant proportion of these sequences are under negative selection. We next characterize all possible single base pair mutations that can lead to the appearance of a nullomer in the human genome, observing a significantly higher number of mutations than expected by chance for specific nullomer sequences in transposable elements, likely due to their suppression. We also annotate nullomers that appear due to naturally occurring variants and show that a subset of them can be used to distinguish between different human populations. Moreover, we demonstrate that nullomers can also be created due to somatic mutations in cancer. We refer to the subset of nullomers that are found recurrently in one cancer type as neomers. We show that we can distinguish twenty-one different tumor-types with higher accuracy than state-of-the-art methods using a neomer-based classifier. Refinement of this classifier via supervised learning identified additional cancer features with even greater precision. We also demonstrate that neomers can precisely diagnose cancer from cfDNA in liquid biopsy samples. Finally, we show that neomers can be used to detect cancer-associated non-coding mutations affecting gene regulatory activity.