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Host-microbiome protein-protein interactions capture mechanisms in human disease

View ORCID ProfileJuan Felipe Beltrán, View ORCID ProfileIlana Lauren Brito
doi: https://doi.org/10.1101/821926
Juan Felipe Beltrán
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY
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Ilana Lauren Brito
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY
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  • For correspondence: ibrito@cornell.edu
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Abstract

Host-microbe interactions are crucial for normal physiological and immune system development and are implicated in a wide variety of diseases, including inflammatory bowel disease (IBD), obesity, colorectal cancer (CRC), and type 2 diabetes (T2D). Despite large-scale case-control studies aimed at identifying microbial taxa or specific genes involved in pathogeneses, the mechanisms linking them to disease have thus far remained elusive. To better identify potential mechanisms linking human-associated bacteria with host health, we leveraged publicly-available interspecies protein-protein interaction (PPI) data to identify clusters of homologous microbiome-derived proteins that bind human proteins. By detecting human-interacting bacterial genes in metagenomic case-control microbiome studies and applying a tailored machine learning algorithm, we are able to identify bacterial-human PPIs strongly linked with disease. In 9 independent case studies, we discover the microbiome broadly targets human immune, oncogenic, apoptotic, and endocrine signaling pathways, among others. This host-centric analysis strategy illuminates human pathways targeted by the commensal microbiota, provides a mechanistic hypothesis-generating platform for any metagenomics cohort study, and extensively annotates bacterial proteins with novel host-relevant functions.

Footnotes

  • Conflict of Interest Provisional patents have been filed for both the process described in this paper and therapeutic/diagnostic protein candidates found through this process through Cornell University. Inventors: Ilana Brito and Juan Felipe Beltrán.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 29, 2019.
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Host-microbiome protein-protein interactions capture mechanisms in human disease
Juan Felipe Beltrán, Ilana Lauren Brito
bioRxiv 821926; doi: https://doi.org/10.1101/821926
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Host-microbiome protein-protein interactions capture mechanisms in human disease
Juan Felipe Beltrán, Ilana Lauren Brito
bioRxiv 821926; doi: https://doi.org/10.1101/821926

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