Biology subjects

Shalon, D.

Publications and source records attributed to Shalon, D..

3 recordsLinked to original sources

bioRxiv2026

FastaLake selects compact metaproteomic databases from large sequence reservoirs by de novo peptide lookup

Metaproteomics analyses require protein sequence databases, yet the microbial proteins present in complex communities are not known in advance. Searching reference catalogs containing hundreds of millions of candidate sequences reduces identification sensitivity, while generating sample-specific databases through metagenomic sequencing adds time and cost. We introduce FastaLake, a computational workflow that uses full-length de novo peptide predictions by AlphaNovo to retrieve complete proteins from broad sequence resources and selects compact databases for conventional searching. In a defined eight-member community, FastaLake approached reference-search peptide yields without knowing its members. Using public sequence catalogs, FastaLake identified about as many peptides as matched metagenomic databases in two stool cohorts and 20-35% more in intestinal fluid at the same nominal 1% peptide false discovery rate. The resulting proteomes reveal personal functional profiles that persist across intestinal regions despite differences in leading species between intestinal fluid and stool. DNA, RNA and protein profiles agreed on broad differences between patients but only weakly on individual functions. All 726 acquisition-specific databases were smaller than the human reference proteome. Compact databases allowed non-specific searches of all 347 CapScan acquisitions, revealing histidine enrichment at peptide C termini in intestinal fluid. FastaLake enables metaproteomics analysis without matched metagenomic sequencing by constructing search databases from sequence resources and de novo peptide sequencing.

bioinformatics↗

bioRxiv2024

Improved mouse models of the small intestine microbiota using region-specific sampling from humans

Our understanding of region-specific microbial function within the gut is limited due to reliance on stool. Using a recently developed capsule device, we exploit regional sampling from the human intestines to develop models for interrogating small intestine (SI) microbiota composition and function. In vitro culturing of human intestinal contents produced stable, representative communities that robustly colonize the SI of germ-free mice. During mouse colonization, the combination of SI and stool microbes altered gut microbiota composition, functional capacity, and response to diet, resulting in increased diversity and reproducibility of SI colonization relative to stool microbes alone. Using a diverse strain library representative of the human SI microbiota, we constructed defined communities with taxa that largely exhibited the expected regional preferences. Response to a fiber-deficient diet was region-specific and reflected strain-specific fiber-processing and host mucus-degrading capabilities, suggesting that dietary fiber is critical for maintaining SI microbiota homeostasis. These tools should advance mechanistic modeling of the human SI microbiota and its role in disease and dietary responses.

microbiology↗

bioRxiv2022

Profiling of the human intestinal microbiome and bile acids under physiologic conditions using an ingestible sampling device

The spatiotemporal structure of the human microbiome and metabolome reflects and determines regional intestinal physiology and may have implications for disease. Yet, we know little about the distribution of microbes and their products in the gut because of reliance on stool samples and limited access only to some regions of the gut using endoscopy in fasting or sedated individuals. To address these deficiencies, we developed and evaluated a safe, ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. The collection of 240 intestinal samples from 15 healthy individuals using the device revealed significant differences between microbes and metabolites present in the intestines versus stool. Certain microbial taxa were differentially enriched, and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Overall, we identified heterogeneous intestinal profiles of bacterial taxa and metabolites indicating that non-invasive multi-regional sampling of the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.

microbiology↗