Resurrecting Extinct Antimicrobial Peptides with Machine Learning

Resurrecting Extinct Antimicrobial Peptides with Machine Learning

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Can bringing back extinct proteins help solve antimicrobial resistance? In a recent paper, a research team developed an open-source ML tool to artificially cleave proteins into peptides and evaluate the peptides for antimicrobial properties. They applied their method to modern human proteins, as well as the proteomes of Neanderthals and Denisovans, to broaden the search for new antimicrobial molecules.

What is Molecular De-Extinction?

While many organisms have gone extinct, their genomes haven’t. Ancient DNA (aDNA) analysis is an active area of research, often applied to study human evolution. While there are many challenges around working with aDNA, including degradation and contamination of genetic material, as well as incomplete genomes, substantial fragments of DNA sequences have been recovered from extinct species and sequenced.

Molecular de-extinction refers to the process of “resurrecting” molecules like nucleic acids and proteins that were found in extinct organisms, but are no longer encoded by living organisms. The hypothesis is that biomolecules that were beneficial for survival in the past, through periods of climate change or to combat infectious disease, for example, may still confer a benefit today.

Prospecting for Antimicrobial Peptides Using Machine Learning

There is a unique subset of the human proteome, called the cryptome, that encodes antimicrobial peptides (AMPs), a highly conserved form of host defense and innate immunity. AMPs are released from their precursor proteins through cleavage by host and pathogen proteases. Useful AMPs have been discovered across diverse forms of life, and in a recent paper published in Cell Host and Microbe, Maasch et al. developed a machine learning pipeline to search extinct and modern human proteomes for AMPs.

The open-source Python pipeline, called panCleave, uses a pan-protease cleavage site classifier to computationally “digest” human proteins into peptide fragments. The authors experimentally validated panCleave in modern humans and in the proteomes of Neanderthals and Denisovans, our closest extinct relatives. panCleave identified peptides within known AMP precursor protein groups, and the hits it generated were unique from other human protease-specific cleavage predictors.

The Challenge of Antibiotic Resistance

Introducing “paleoproteome mining” into the toolbox of searching for new AMPs and antibiotics comes at a time when new antimicrobials are desperately needed. Antimicrobial resistance is a global crisis, and computer-aided protein design and discovery tools promise to help accelerate the search for new antimicrobial molecules. Whether they come from extinct or existing organisms, or are completely artificially generated, any new antimicrobials will be invaluable.

Outsourcing Bioinformatics Analysis: How Bridge Informatics Can Help

Groundbreaking studies like these are made possible by technological advances making biological data generation, storage and analysis faster and more accessible than ever before. From pipeline development and software engineering to deploying existing bioinformatics tools, Bridge Informatics can help you on every step of your research journey.

As experts across data types from leading sequencing platforms, we can help you tackle the challenging computational tasks of storing, analyzing and interpreting genomic and transcriptomic data. Bridge Informatics’ bioinformaticians are trained bench biologists, so they understand the biological questions driving your computational analysis. Click here to schedule a free introductory call with a member of our team.

Jane Cook, Biochemist & Content Writer, Bridge Informatics

Jane Cook, the leading Content Writer for Bridge Informatics, has written over 100 articles on the latest topics and trends for the bioinformatics community. Jane’s broad and deep interdisciplinary molecular biology experience spans developing biochemistry assays to genomics. Prior to joining Bridge, Jane held research assistant roles in biochemistry research labs across a variety of therapeutic areas. While obtaining her B.A. in Biochemistry from Trinity College in Dublin, Ireland, Jane also studied journalism at New York University’s Arthur L. Carter Journalism Institute. As a native Texan, she embraces any challenge that comes her way. Jane hails from Dallas but returns to Ireland any and every chance she gets. If you’re interested in reaching out, please email [email protected] or [email protected].

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