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Peterson, C. B.

Publications and source records attributed to Peterson, C. B..

2 recordsLinked to original sources

TARO: tree-aggregated factor regression for microbiome data integration

MotivationAlthough the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. However, this remains challenging to the high dimensionality, compositionality, and rare features found in microbiome profiling data. These challenges necessitate the use of methods that can achieve structured sparsity in learning cross-platform association patterns. ResultsWe propose Tree-Aggregated factor RegressiOn (TARO) for the integration of microbiome and metabolomic data. We leverage information on the phylogenetic tree structure to flexibly aggregate rare features. We demonstrate through simulation studies that TARO accurately recovers a low-rank coefficient matrix and identifies relevant features. We applied TARO to microbiome and metabolomic profiles gathered from subjects being screened for colorectal cancer to understand how gut microrganisms shape intestinal metabolite abundances. Availability and implementationThe R package TARO implementing the proposed methods is available online at https://github.com/amishra-stats/taro-package.

bioinformatics↗

Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment

Not all cancer patients with severe neutropenia develop fever, and the fecal microbiome may play a role. In neutropenic hematopoietic cell transplant patients (n=119), 63 (53%) developed a subsequent fever and had increased fecal Akkermansia muciniphila, a mucus-degrading bacteria (p=0.006, corrected for multiple comparisons). In mouse models, two therapies, irradiation and melphalan, similarly expanded A. muciniphila. Dietary restriction of unirradiated mice also expanded A. muciniphila and thinned the colonic mucus layer. Azithromycin treatment depleted A. muciniphila and preserved colonic mucus. Dietary restriction raised colonic luminal pH and reduced acetate, propionate, and butyrate. Culturing A. muciniphila with lower pH and increased propionate prevented utilization of mucin. Treating irradiated mice with azithromycin or propionate preserved the mucus layer, lessened hypothermia, and reduced inflammatory cytokines in the colon. These results suggest that diet, metabolites and colonic mucus link the microbiome to neutropenic fever, and could guide future microbiome-based preventive strategies.

microbiology↗