Human Genomics - Projects

Project Principal Investigator
Transformative Research Award (TR01) Julie Dunning Hotopp PhD
Cancer Health Disparities Timothy O'Connor PhD
Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD) Timothy O'Connor PhD
Trans-Omics for Precision Medicine (TOPMed) Project Timothy O'Connor PhD

Transformative Research Award (TR01) — Extent & Significance of Bacterial DNA Integrations in the Human Cancer Genome.

The integration of exogenous DNA into the human genome can cause somatic mutations associated with oncogenesis. For example, the insertion of HPV DNA into human chromosomes is the single most important event leading to tumorigenesis in cervical cancer. It is also now preventable with vaccines against HPV. In contrast to viral DNA integrations, the instances and repercussions of bacterial DNA integration into the somatic human genome are less clear. This project has three objectives aimed at addressing our gap in knowledge about bacterial DNA integrations. First, virtual machines will be developed for LGTSeek and LGTview, our bioinformatics tools that we have used previously to detect bacterial DNA integrations in human genome sequencing projects. LGTSeek and LGTView will be used to further interrogate publicly available cancer genome data where such integrations are likely to occur because the tissues are exposed to the microbiome (e.g. colon). Second, genome and transcriptome sequencing will be undertaken of new stomach adenocarcinoma samples and acute myeloid leukemia samples in order to reproduce previous results that suggest the presence of bacterial DNA integrations, includinge control samples with exogenous bacterial nucleic acids added to the sample in order to quantify the formation of chimeras in modern sequencing techniques. Third, the effect that previously detected bacterial DNA integrations have on transcription will be interrogated using luciferase reporter constructs and the CRISPR/Cas9 system. Collectively, this research is expected to improve our understanding of the extent and significance of bacterial DNA integrations in the somatic human genome.


Cancer Health Disparities

Certain cancer types have stratified risk between people of different ancestries. In addition to issues of socioeconomic disparities, molecular diseases to specific populations have been traditionally understudied. Dr. O’Connor and his group are using population genetics approaches to characterize key cancer resources, including cancer cell lines, and are developing a cancer analysis pipeline so that clinicians and researchers working with non-European populations can gain added value from our understanding of evolutionary processes.


Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD)

PD is understudied in Latin America, especially for individuals with a lot of Native American ancestry. To remedy this issue, in collaboration with Dr. Ignacio Mata (hyperlink: at the Cleveland Clinic, Dr. O’Connor and his group are performing the first GWAS of PD Latino patients and evaluating polygenic risk scores for this group. (see


Trans-Omics for Precision Medicine (TOPMed) Project

This large collaborative study, funded by NHLBI, seeks to sequence about 200K individuals and complement their deep heart, lung, and blood phenotypes with multi-omics profiles (see Dr. O’Connor’s group is leading analyses to answer questions in large-scale population genetics, providing new insights into population structure, rare variation, and quantitative genetics. They are developing a machine learning-based method to integrate multi-omics profiles in the context of recent evolution.