Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients’ smoking status, and the response to immunotherapy.
Plant photosynthetic (thylakoid) membranes are organized into complex networks that are differentiated into 2 distinct morphological and functional domains called grana and stroma lamellae. How the 2 domains join to form a continuous lamellar system has been the subject of numerous studies since the mid-1950s. Using different electron tomography techniques, we found that the grana and stroma lamellae are connected by an array of pitch-balanced right- and left-handed helical membrane surfaces of different radii and pitch. Consistent with theoretical predictions, this arrangement is shown to minimize the surface and bending energies of the membranes. Related configurations were proposed to be present in the rough endoplasmic reticulum and in dense nuclear matter phases theorized to exist in neutron star crusts, where the right- and left-handed helical elements differ only in their handedness. Pitch-balanced helical elements of alternating handedness may thus constitute a fundamental geometry for the efficient packing of connected layers or sheets.
Information theoretic approaches are ubiquitous and effective in a wide variety of bioinformatics applications. In comparative genomics, alignment-free methods, based on short DNA words, or k-mers, are particularly powerful. We evaluated the utility of varying k-mer lengths for genome comparisons by analyzing their sequence space coverage of 5805 genomes in the KEGG GENOME database. In subsequent analyses on four k-mer lengths spanning the relevant range (11, 21, 31, 41), hierarchical clustering of 1634 genus-level representative genomes using pairwise 21- and 31-mer Jaccard similarities best recapitulated a phylogenetic/taxonomic tree of life with clear boundaries for superkingdom domains and high subtree similarity for named taxons at lower levels (family through phylum). By analyzing ~14.2M prokaryotic genome comparisons by their lowest-common-ancestor taxon levels, we detected many potential misclassification errors in a curated database, further demonstrating the need for wide-scale adoption of quantitative taxonomic classifications based on whole-genome similarity.
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