No abstract

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. We trained a classifier using the normalized copy numbers of 33 HMI-associated metabolic modules. Our classifier not only distinguished states of health versus IBD, but it also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.

No abstract

We consider the problem of testing for a difference in means between clusters of observations identified via k-means clustering. In this setting, classical hypothesis tests lead to an inflated Type I error rate. To overcome this problem, we take a selective inference approach. We propose a finite-sample p-value that controls the selective Type I error for a test of the difference in means between a pair of clusters obtained using k-means clustering, and show that it can be efficiently computed. We apply our proposal in simulation, and on hand-written digits data and single-cell RNA-sequencing data.