A tantalizing question in cellular physiology is whether the cellular state and environmental conditions can be inferred by the expression signature of an organism. To investigate this relationship, we created an extensive normalized gene expression compendium for the bacterium Escherichia coli that was further enriched with meta-information through an iterative learning procedure. We then constructed an ensemble method to predict environmental and cellular state, including strain, growth phase, medium, oxygen level, antibiotic and carbon source presence. Results show that gene expression is an excellent predictor of environmental structure, with multi-class ensemble models achieving balanced accuracy between 70.0% (±3.5%) to 98.3% (±2.3%) for the various characteristics. Interestingly, this performance can be significantly boosted when environmental and strain characteristics are simultaneously considered, as a composite classifier that captures the inter-dependencies of three characteristics (medium, phase and strain) achieved 10.6% (±1.0%) higher performance than any individual models. Contrary to expectations, only 59% of the top informative genes were also identified as differentially expressed under the respective conditions. Functional analysis of the respective genetic signatures implicates a wide spectrum of Gene Ontology terms and KEGG pathways with condition-specific information content, including iron transport, transferases, and enterobactin synthesis. Further experimental phenotypic-to-genotypic mapping that we conducted for knock-out mutants argues for the information content of top-ranked genes. This work demonstrates the degree at which genome-scale transcriptional information can be predictive of latent, heterogeneous and seemingly disparate phenotypic and environmental characteristics, with far-reaching applications.

A tantalizing question in evolutionary biology is whether evolution can be predicted from past experiences. To address this question, we created a coherent compendium of more than 15,000 mutation events for the bacterium Escherichia coli under 178 distinct environmental settings. Compendium analysis provides a comprehensive view of the explored environments, mutation hotspots and mutation co-occurrence. While the mutations shared across all replicates decrease with the number of replicates, our results argue that the pairwise overlapping ratio remains the same, regardless of the number of replicates. An ensemble of predictors trained on the mutation compendium and tested in forward validation over 35 evolution replicates achieves a 49.2 ± 5.8% (mean ± std) precision and 34.5 ± 5.7% recall in predicting mutation targets. This work demonstrates how integrated datasets can be harnessed to create predictive models of evolution at a gene level and elucidate the effect of evolutionary processes in well-defined environments.

A significant obstacle in training predictive cell models is the lack of integrated data sources. We develop semi-supervised normalization pipelines and perform experimental characterization (growth, transcriptional, proteome) to create Ecomics, a consistent, quality-controlled multi-omics compendium for Escherichia coli with cohesive meta-data information. We then use this resource to train a multi-scale model that integrates four omics layers to predict genome-wide concentrations and growth dynamics. The genetic and environmental ontology reconstructed from the omics data is substantially different and complementary to the genetic and chemical ontologies. The integration of different layers confers an incremental increase in the prediction performance, as does the information about the known gene regulatory and protein-protein interactions. The predictive performance of the model ranges from 0.54 to 0.87 for the various omics layers, which far exceeds various baselines. This work provides an integrative framework of omics-driven predictive modelling that is broadly applicable to guide biological discovery.

Here we report a draft genome sequence of Azoarcus communis SWub3, a nitrogen-fixing bacterium isolated from root tissues of Kallar grass in Pakistan.