Combining whole exome sequencing, transcriptome profiling, and T cell repertoire analysis, we investigate the spatial features of surgically-removed biopsies from multiple loci in tumor masses of 15 patients with non-small cell lung cancer (NSCLC). This revealed that the immune microenvironment has high spatial heterogeneity such that intratumoral regional variation is as large as inter-personal variation. While the local total mutational burden (TMB) is associated with local T-cell clonal expansion, local anti-tumor cytotoxicity does not directly correlate with neoantigen abundance. Together, these findings caution against that immunological signatures can be predicted solely from TMB or microenvironmental analysis from a single locus biopsy.

Summary Many studies have investigated patterns in the near‐surface soil microbial community over large spatial scales. However, less is known about variation in subsurface (15–30 cm of depth) microbial communities. Here we studied depth profiles of microbial communities in high‐elevation soils from Tibet. The relative abundance of Acidobacteria, Chloroflexi and Alphaproteobacteria was higher in near‐surface layers, while the relative abundance of Actinobacteria, Gemmatimonadetes and Betaproteobacteria was higher in the subsurface samples. The microbial community structure was distinct between the surface and subsurface soil layers, strongly correlating with variation in total carbon (TC) and carbon to nitrogen ratio (C/N). The differences in the microbial community between the layers were about the same as the horizontal differences between sites separated by many kilometers. Overall, we found that TC and C/N were the best predictors for both surface and subsurface microbial community distribution. Exploration of the relative contribution of distance and environmental variables to community composition suggests that the contemporary environment is the primary driver of microbial distribution in this region. Reflecting niche conservatism in evolution, the microbial communities in each soil site and layer tended to be more phylogenetically clustered than expected by chance, and surface soil layer samples were more likely to be clustered than subsurface samples.

The giant panda feeds almost exclusively on bamboo, a diet highly enriched in lignin and cellulose, but is characterized by a digestive tract similar to carnivores. It is still large unknown if and how the giant panda gut microbiota contributes to lignin and cellulose degradation. Here we show the giant pandas’ gut microbiota does not significantly contribute to cellulose and lignin degradation. We found that no operational taxonomic unit had a nearest neighbor identified as a cellulolytic species or strain with a significant higher abundance in juvenile than cubs, a very low abundance of putative lignin and cellulose genes existed in part of analyzing samples but a significant higher abundance of genes involved in starch and hemicellulose degradation in juveniles than cubs. Moreover, a significant lower abundance of putative cellulolytic genes and a significant higher abundance of putative α-amylase and hemicellulase gene families were present in giant pandas than in omnivores or herbivores.

The changes of gastric microbiome across stages of neoplastic progression remain poorly understood, especially for intraepithelial neoplasia (IN) which has been recognized as a phenotypic bridge between atrophic/intestinal metaplastic lesions and invasive cancer. The gastric microbiota was investigated in 30 healthy controls (HC), 21 nonatrophic chronic gastritis (CG), 27 gastric intestinal metaplasia (IM), 25 IN, and 29 gastric cancer (GC) patients by 16S rRNA gene profiling. The bacterial diversity, and abundances of phyla Armatimonadetes, Chloroflexi, Elusimicrobia, Nitrospirae, Planctomycetes, Verrucomicrobia, and WS3 reduced progressively from CG, through IM, IN to GC. Actinobacteria, Bacteriodes, Firmicutes, Fusobacteria, SR1, and TM7 were enriched in the IN and GC. At the community level, the proportions of Grampositive and anaerobic bacteria increased in the IN and GC compared to other histological types, whereas the aerobic and facultatively anaerobic bacteria taxa were significantly reduced in GC. Remarkable changes in the gastric microbiota functions were detected after the formation of IN. The reduced nitrite-oxidizing phylum Nitrospirae together with a decreased nitrate/nitrite reductase functions indicated nitrate accumulation during neoplastic progression. We constructed a random forest model, which had a very high accuracy (AUC > 0.95) in predicating the histological types with as low as five gastric bacterial taxa. In summary, the changing patterns of the gastric microbiota composition and function are highly indicative of stages of neoplastic progression.