In their natural environments, microorganisms form complex systems of interactions. Understating the structure and organization of bacterial communities is likely to have broad medical and ecological consequences, yet a comprehensive description of the network of environmental interactions is currently lacking. Here, we mine co-occurrences in the scientific literature to construct such a network and demonstrate an expected pattern of association between the species’ lifestyle and the recorded number of co-occurring partners. We further focus on the well-annotated gut community and show that most co-occurrence interactions of typical gut bacteria occur within this community. The network is then clustered into species-groups that significantly correspond with natural occurring communities. The relationships between resource competition, metabolic yield and growth rate within the clusters correspond with the r/K selection theory. Overall, these results support the constructed clusters as a first approximation of a bacterial ecosystem model. This comprehensive collection of predicted communities forms a new data resource for further systematic characterization of the ecological design principals shaping communities. Here, we demonstrate its utility for predicting cooperation and inhibition within communities.

Deciphering the modular organization of metabolic networks and understanding how modularity evolves have attracted tremendous interest in recent years. Here, we present a comprehensive large scale characterization of modularity across the bacterial tree of life, systematically quantifying the modularity of the metabolic networks of >300 bacterial species. Three main determinants of metabolic network modularity are identified. First, network size is an important topological determinant of network modularity. Second, several environmental factors influence network modularity, with endosymbionts and mammal-specific pathogens having lower modularity scores than bacterial species that occupy a wider range of niches. Moreover, even among the pathogens, those that alternate between two distinct niches, such as insect and mammal, tend to have relatively high metabolic network modularity. Third, horizontal gene transfer is an important force that contributes significantly to metabolic modularity. We additionally reconstruct the metabolic network of ancestral bacterial species and examine the evolution of modularity across the tree of life. This reveals a trend of modularity decrease from ancestors to descendants that is likely the outcome of niche specialization and the incorporation of peripheral metabolic reactions.horizontal gene transfer ͉ lateral gene transfer ͉ systems biology ͉ bacterial evolution ͉ network modules M odularity is considered to be one of the main organizing principles of biological networks (1, 2). A biological network module consists of a set of elements (e.g., proteins/ reactions) that form a coherent structural subsystem and have a distinct function. Several studies have explored the role of modularity and network organization in various proteininteraction and regulatory cellular networks (3-10). Focusing specifically on modularity in metabolic networks (which is also the subject of this article), the metabolic networks of 43 distinct organisms were shown to be organized in many small, highly connected topologic modules that hierarchically combine into larger units (11). The functional and evolutionary modularity of the human metabolic network was also investigated from a topological perspective by using network decomposition (12). The network was shown to be organized in a highly modular way into basic core metabolism modules and peripheral modules that have specialized functions and evolve at a faster rate.Considering the evolution of modularity, two major hypotheses have been proposed: the ''evolution of evolvability'' and the congruence principle (13). The first posits that there is positive selection favoring modularity because it enhances evolvability by enabling evolutionary changes to take place in confined modules while preserving global cellular functions (14, 15). The second maintains that, although modularity is not directly selected for, there is nevertheless an evolutionary congruence between modularity and other directly selectable properties. Such properties may include accelerat...

During mammalian development, differences in chromatin state coincide with cellular differentiation and reflect changes in the gene regulatory landscape1. In the developing brain, cell fate specification and topographic identity are important for defining cell identity2 and confer selective vulnerabilities to neurodevelopmental disorders3. Here, to identify cell-type-specific chromatin accessibility patterns in the developing human brain, we used a single-cell assay for transposase accessibility by sequencing (scATAC-seq) in primary tissue samples from the human forebrain. We applied unbiased analyses to identify genomic loci that undergo extensive cell-type- and brain-region-specific changes in accessibility during neurogenesis, and an integrative analysis to predict cell-type-specific candidate regulatory elements. We found that cerebral organoids recapitulate most putative cell-type-specific enhancer accessibility patterns but lack many cell-type-specific open chromatin regions that are found in vivo. Systematic comparison of chromatin accessibility across brain regions revealed unexpected diversity among neural progenitor cells in the cerebral cortex and implicated retinoic acid signalling in the specification of neuronal lineage identity in the prefrontal cortex. Together, our results reveal the important contribution of chromatin state to the emerging patterns of cell type diversity and cell fate specification and provide a blueprint for evaluating the fidelity and robustness of cerebral organoids as a model for cortical development.

Human Leukocyte Antigen class I (HLA) restricted CD8+ T lymphocyte (CTL) responses are critical to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, since these variants can also reduce intrinsic viral fitness. To address this question, we here develop a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4 decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to expression of certain HLA alleles. Thus, viral pre-adaptation exploits “holes” in the immune response. Accounting for these holes may be critical for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies requiring broad CTL responses to achieve successful eradication of HIV reservoirs.