Project description:A cyanobacterium, Thermosynechococcus elongatus BP1, was cultured with a heterotroph, Meiothermus ruber strain A, under a variety of conditions. A gene co-expression approach was used to infer a network of T. elongatus and M. ruber genes, with a focus on those genes from different species that were co-expressed, highlighting potential points of coordination and interaction.
Project description:The advent of high-throughput 'omics approaches coupled with computational analyses to reconstruct individual genomes from metagenomes provides a basis for species-resolved functional studies. Here, a mutual information approach was applied to build a gene association network of a commensal consortium, in which a unicellular cyanobacterium Thermosynechococcus elongatus BP1 supported the heterotrophic growth of Meiothermus ruber strain A. Specifically, we used the context likelihood of relatedness (CLR) algorithm to generate a gene association network from 25 transcriptomic datasets representing distinct growth conditions. The resulting interspecies network revealed a number of linkages between genes in each species. While many of the linkages were supported by the existing knowledge of phototroph-heterotroph interactions and the metabolism of these two species several new interactions were inferred as well. These include linkages between amino acid synthesis and uptake genes, as well as carbohydrate and vitamin metabolism, terpenoid metabolism and cell adhesion genes. Further topological examination and functional analysis of specific gene associations suggested that the interactions are likely to center around the exchange of energetically costly metabolites between T. elongatus and M. ruber. Both the approach and conclusions derived from this work are widely applicable to microbial communities for identification of the interactions between species and characterization of community functioning as a whole.
Project description:We report the development of a new computational method to assess differences in cell-cell interactions between conditions through utilizing single-cell RNA sequencing data. The pipeline, known as Cell Interaction Network Inference from Single-cell Expression data (CINS), combines Bayesian network analysis with regression-based modeling to identify differential cell type interactions and the proteins that underlie these interactions.
Project description:A dominant loss of function mutation in myo-inositol phosphate synthase gene and recessive loss of function mutations in two multidrug resistant protein type-ABC transporter genes not only reduce the seed phytic acid levels in soybean, but also affect the pathways associated with seed development, ultimately resulting in low emergence. To understand the regulatory mechanisms and identify key genes that intervene in the seed development process in low phytic acid crops, we performed computational inference of gene regulatory networks in low and normal phytic acid soybeans using a time course transcriptomic data and multiple network inference algorithms. We identified several transcription factors and their regulatory interactions with genes that have functions in myo-inositol biosynthesis, auxin-ABA signaling and seed dormancy. We validated the predicted regulatory network by comparing it with published regulatory interactions in Arabidopsis. Some regulatory interactions were found in the low phytic acid mutants but not in non-mutant plants. These findings provide important hypotheses on expression regulation of myo-inositol metabolism, and phytohormone signaling in developing low phytic acid soybeans. The computational pipeline used for unsupervised network learning in this study is provided as open source software and is freely available at https://lilabatvt.github.io/LPANetwork/.
Project description:Gene regulatory network inference is essential to uncover complex relationships among gene pathways and inform downstream experiments, ultimately enabling regulatory network re-engineering. Network inference from transcriptional time-series data requires accurate, interpretable, and efficient determination of causal relationships among thousands of genes. Here, we develop Bootstrap Elastic net regression from Time Series (BETS), a statistical framework based on Granger causality for the recovery of a directed gene network from transcriptional time-series data. BETS uses elastic net regression and stability selection from bootstrapped samples to infer causal relationships among genes. BETS is highly parallelized, enabling efficient analysis of large transcriptional data sets. We show competitive accuracy on a community benchmark, the DREAM4 100-gene network inference challenge, where BETS is one of the fastest among methods of similar performance and additionally infers whether the causal effects are activating or inhibitory. We apply BETS to transcriptional time-series data of 2,768 differentially-expressed genes from A549 cells exposed to glucocorticoids over a period of 12 hours. We identify a network of 2,768 genes and 31,945 directed edges (FDR <= 0.2). We validate inferred causal network edges using two external data sources: overexpression experiments on the same glucocorticoid system, and genetic variants associated with inferred edges in primary lung tissue in the Genotype-Tissue Expression (GTEx) v6 project. BETS is available as an open source software package at https://github.com/lujonathanh/BETS
Project description:Gene regulatory network inference is essential to uncover complex relationships among gene pathways and inform downstream experiments, ultimately enabling regulatory network re-engineering. Network inference from transcriptional time-series data requires accurate, interpretable, and efficient determination of causal relationships among thousands of genes. Here, we develop Bootstrap Elastic net regression from Time Series (BETS), a statistical framework based on Granger causality for the recovery of a directed gene network from transcriptional time-series data. BETS uses elastic net regression and stability selection from bootstrapped samples to infer causal relationships among genes. BETS is highly parallelized, enabling efficient analysis of large transcriptional data sets. We show competitive accuracy on a community benchmark, the DREAM4 100-gene network inference challenge, where BETS is one of the fastest among methods of similar performance and additionally infers whether the causal effects are activating or inhibitory. We apply BETS to transcriptional time-series data of 2,768 differentially-expressed genes from A549 cells exposed to glucocorticoids over a period of 12 hours. We identify a network of 2,768 genes and 31,945 directed edges (FDR <= 0.2). We validate inferred causal network edges using two external data sources: overexpression experiments on the same glucocorticoid system, and genetic variants associated with inferred edges in primary lung tissue in the Genotype-Tissue Expression (GTEx) v6 project. BETS is available as an open source software package at https://github.com/lujonathanh/BETS
Project description:we develop an interspecies pluripotent stem cell (PSC) co-culture strategy and uncover a previously unknown mode of cell competition. Interspecies PSC competition occurs during primed but not naive pluripotency, and between evolutionarily distant species. We identified genes related to NF-κB signaling pathways, among others, were upregulated in loser cells and genetic inactivation of RELA, a core component of canonical NF-κB pathway, could overcome interspecies PSC competition. We further showed that an upstream regulator of the NF-κB signaling, MYD88 innate immune signal transduction adaptor, was also involved in promoting loser PSC elimination. Suppressing interspecies PSC competition via genetic perturbation of MYD88 or P65 improved engraftment of human cells in early post-implantation mouse embryos. Our study discovers a new paradigm of cell competition and paves the way for studying evolutionarily conserved cell competition mechanisms during early mammalian development. Strategies developed here to overcome interspecies PSC competition may facilitate interspecies organogenesis between evolutionary distant species, including humans.