A whole organism screening platform identifies gut microbiome microproteins that modulate host metabolism
Short, N. E.; Warren, E. C.; Porter, I. E.; Pinto, Y.; Rodriguez, J.; Sarkisyan, K.; Bhatt, A. S.; Brown, A.; Riglar, D. T.
Show abstract
Advances in metagenomic sequencing over the past two decades have identified vast numbers of previously uncharacterised small open reading frames that may encode microproteins (<50aa). Although computational tools have accelerated gene sequence prediction from metagenomic data, the function of most annotated proteins remains unknown and untested, especially in the context of host-microbiome interactions. Here, we present a scalable phenotypic screening pipeline to identify gut microbiome-derived proteins that modulate host function. Using the nematode worm Caenorhabditis elegans as a whole animal model that is amenable to systematic screening approaches, our pipeline integrates high-throughput cloning, expression and delivery to worms via feeding, followed by behavioural phenomics screening. We apply this approach to a pilot library of 126 uncharacterised microproteins (< 50 aa) from healthy human gut metagenomes, identifying a set of high-interest targets with potential activity and ultimately validating a microprotein that modulates host fatty acid metabolism when expressed. With protein-based therapies increasingly recognised as a promising alternative to traditional small molecules, this work highlights the potential of a target-agnostic approach for the systematic screening and discovery of novel bioactive proteins.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Antimicrobial activity of iron-depriving pyoverdines against human opportunistic pathogens 95%
- Structure-Function analysis of Lactiplantibacillus plantarum DltE reveals D-alanylated lipoteichoic acids as direct symbiotic cues supporting Drosophila juvenile growth 94%
- Amoxicillin-resistant Streptococcus pneumoniae can be resensitized by targeting the mevalonate pathway as indicated by sCRilecs-seq 94%
Similar papers in this journal
- Bacterial processing of glucose modulates C. elegans lifespan and healthspan 94%
- The immunomodulatory p43 secreted protein of Trichuris whipworm parasites is a lipid carrier that binds signalling lipids and precursors 93%
- A quiescent state following mild sensory arousal in Caenorhabditis elegans is potentiated by stress 93%
Similar papers in this journal
- Genome-wide libraries for protozoan pathogens drug target screening using yeast surface display 93%
- A multiplexed, target-based phenotypic screening platform using CRISPR interference in Mycobacterium abscessus 93%
- Cysteine reactivity profiling identifies host regulators of Mycobacterium tuberculosis replication in human macrophages 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.