# Integrative omics pipeline to identify novel COPD genes and pathways

> **NIH NIH K25** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $188,999

## Abstract

Abstract
Although cigarette smoking is the major risk factor, multiple studies have demonstrated a genetic component to
chronic obstructive pulmonary disease (COPD) susceptibility. Genome Wide Association Studies (GWAS)
have identified Single Nucleotide Polymorphisms (SNPs) that have a significant association with COPD.
Beyond the informative top findings, many GWAS results are below the genome-wide threshold for significance
and are typically ignored. The central hypothesis of this study is that sub-threshold GWAS SNPs confer
susceptibility to COPD. We will develop a publicly available ensemble analysis tool to elucidate susceptibility
factors from prior GWAS using genomic, epigenomic and genetic data in lung tissue. This integrative omics
method will aggregate the gene expression effects from all potentially relevant SNPs by extracting the
additional genetic and genomic signals contained in the sub-threshold results, from the biological and technical
noise. The electrical engineering background of the applicant provides a valuable perspective for the extraction
of the signals from noise, as well as experience in the creation of solutions from custom-tailored building
blocks. His M.S. degrees in Biotechnology and Bioinformatics provide a foundation for biomedical research
that has been centered on COPD, in particular the analysis of multidimensional omics and phenotype data.
Training and mentorship within the Channing Division of Network Medicine (CDNM) at Brigham and Women’s
Hospital will impart the necessary knowledge in lung disease biology, statistics, network methods and software
development to succeed in this study and move toward independence. The CDNM has a well-established
research program in respiratory, environmental and genetic epidemiology, pharmacogenetics and genomics,
statistical genetics, bioinformatics, epigenetics and network medicine. This environment provides access to
multiple didactic activities, within the Division and through neighboring institutes, such as seminars and
lectures that will facilitate the applicant's training. The applicant will attain new skills to develop new methods
and adapt existing ones to serve as components in the proposed pipeline. In this study, we will aggregate the
effects of sub-threshold GWAS to implicate genes in the etiology of disease using the Bayesian method
Sherlock, and adapt Sherlock for use with DNA methylation data. We will construct networks using omics data,
and develop methods to observe edge perturbations associated with the genotypes of sub-threshold GWAS
SNPs to highlight their regulatory influence. We will create between-network links based on causal evidence
and identify gene expression regions influenced by epigenetic mediation. The network-based evidence from
these aims will highlight gene communities affecting COPD susceptibility, which may inform the development
of future personalized therapies. Through the proposed career development and mentored research activities,
th...

## Key facts

- **NIH application ID:** 10147908
- **Project number:** 5K25HL136846-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Jarrett MORROW
- **Activity code:** K25 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $188,999
- **Award type:** 5
- **Project period:** 2017-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147908

## Citation

> US National Institutes of Health, RePORTER application 10147908, Integrative omics pipeline to identify novel COPD genes and pathways (5K25HL136846-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10147908. Licensed CC0.

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