# Connecting the universe of proteins to address annotation inequality in the microbial proteome

> **NIH NIH U01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $171,931

## Abstract

Principal Investigator (Wright, Erik S.)
Abstract:
The rapidly increasing number of microbial genomes has revealed an enormous diversity of proteins without
any known function. We still know relatively little about over half the proteins encoded in a typical bacterial
genome, and traditional laboratory techniques are too time consuming to characterize even a small fraction of
the observable universe of proteins. This neglected "dark proteome" potentially contains many important
determinants of virulence, antibiotic resistance, and disease. Casting a light on the dark proteome is possible
through comparative genomics because proteins interacting across evolutionary timescales leave behind a
signature of coevolution that can be used to connect proteins of unknown function with proteins of known
function. This 'guilt-by-association' analysis helps to generate hypotheses about the cellular role of unexplored
proteins. Here, we develop novel methods for quantifying coevolutionary signals, and we apply these methods
to an unprecedently large collection of genomes spanning the microbial tree of life. This project will result in a
network of coevolving genes that we will make publicly accessible as a web tool for biomedical research. To
further harness the power of comparative genomics, we will develop and deploy web applications that provide
deeper insights into the universe of microbial proteins.

## Key facts

- **NIH application ID:** 11144020
- **Project number:** 3U01AI176418-02S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Erik Scott Wright
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $171,931
- **Award type:** 3
- **Project period:** 2023-08-09 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11144020

## Citation

> US National Institutes of Health, RePORTER application 11144020, Connecting the universe of proteins to address annotation inequality in the microbial proteome (3U01AI176418-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11144020. Licensed CC0.

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