I’m interested in computational biology, chromatin structure and 3D DNA organization, machine learning broadly and ml applied to genomics and microbiome genomics, among other things. Here are some of the projects I’ve been working on in the past few years.
CMap at The Broad Institute: Genetic and transcriptional instability alters cancer cell line drug response
Cell lines are a workhorse of cancer research, but they’re not always what you expect. We isolated different clones of supposedly identical cell lines and found wide variation in gene mutations, copy number alterations and gene expression levels. These differences were also associated with differential response to anti-cancer drugs. This could explain some of the difficulties reproducing cell line-based research, but the news isn’t all bad — panels of isogenic-like cell lines could be used to predict mechanisms for new cancer drugs.
CMap at The Broad Institute: Integrating the Connectivity Map and The Cancer Genome Atlas
A statistical method to compare gene expression in two very different sample types: cell lines under treatment with drugs and patient-derived tumor samples. If gene expression in a lung cancer cell line under treatment with a certain drug is anti-correlated with lung cancer patients with a certain mutation, does that drug indicate possible a therapeutic avenue?
Brown Computational Biology Senior Honors Thesis: A multi-scale ensemble model for chromatin conformation
Methods to infer 3D genome structure from 2D HiC contact matrices make assumptions about constant processes at all scales. Here, I developed a statistical method to reconstruct an ensemble of 3D structures representing the underlying population of cells.
Neretti Lab at Brown: Chromatin conformation and senescence
How does the 3D organization of the genome change as cells become replicatively senescent? We found a global decrease in long-range 3D contacts, as well as entire chromatin domains that switched from inactive to active compartments (or vice-versa). Contacts measured with Hi-C were validated on a subset of regions with 3D-FISH.
Brown junior year: Tetranucleotide usage in mycobacteriophage genomes
Working with a stellar group of freshman undergraduates in the Phage Hunters course, we developed a method to compare mycobacteriophage genome sequences using the frequencies of 4-letter DNA words (tetranucleotides). This method highlighted some different evolutionary relationships between groups of phage when compared with standard genome alignment.