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Updated: Apr 7, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Amino acid repeat signatures underlying human-pathogen interactions
Anjali Kumari Singh1, Nagashree Rachote1, Vaidehi Sharma1
1Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517619, Andhra Pradesh, India.
None:
Emerging evidence suggests that amino acid homorepeats (HRs) in proteins (HRPs) contribute to protein interactability. What is the role of HRs in HPIs? We found that pathogens engage physiologically important human HRPs, thereby affecting diverse host physiological processes. From the pathogen standpoint, (1) eukaryotic pathogens engage more HRPs but with host-sparse HRs (HR types that are rare in the host), leading to disparate and discriminate interactions, (2) prokaryotic pathogens engage less HRPs but with host-abundant non-polar HRs via host-protein proxies, bringing about discriminate or promiscuous interactions, and (3) viral pathogens engage more HRPs with host-abundant polar uncharged HRs, affecting promiscuous interactions using host-partner HR tract mimicry. To propel further research, we introduce a resource Hi-PHI (http://hiphi.iisertirupati.ac.in/), cataloging critical information about human and pathogen HRPs and HRs. We propose mechanisms to (1) repurpose drugs targeting human HRPs engaged by pathogens for treating different infections, and (2) exploit HRs and their flanks as targets for pathogen-targeted anti-infectives.
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