The gut microbiome is now widely recognized as a dynamic ecosystem that plays an important role in health and disease 1 . While current sequencing technologies make it possible to estimate relative abundances of host-associated bacteria over time 2, 3 , the biological processes governing their dynamics remain poorly understood. Therefore, as in other ecological systems 4, 5 , it is important to identify quantitative relationships describing global aspects of gut microbiota dynamics. Here we use multiple high-resolution time series data obtained from humans and mice [6][7][8] to demonstrate that despite their inherent complexity, gut microbiota dynamics can be characterized by several robust scaling relationships. Interestingly, these patterns are highly similar to those previously observed across diverse ecological communities and economic systems, including the temporal fluctuations of animal and plant populations 9-12 and the performance of publicly traded companies 13 . Specifically, we find power law relationships describing short-and long-term changes in gut microbiota abundances, species residence and return times, and the connection between the mean and variance of species abundances. The observed scaling relationships are altered in mice receiving different diets and affected by context-specific perturbations in humans. We use these macroecological relationships to reveal specific bacterial taxa whose dynamics are significantly affected by dietary and environmental changes. Overall, our results suggest that a quantitative macroecological framework will be important for characterizing and understanding complex dynamics of microbial communities..

Motivation Gene regulatory networks define regulatory relationships between transcription factors and target genes within a biological system, and reconstructing them is essential for understanding cellular growth and function. Methods for inferring and reconstructing networks from genomics data have evolved rapidly over the last decade in response to advances in sequencing technology and machine learning. The scale of data collection has increased dramatically; the largest genome-wide gene expression datasets have grown from thousands of measurements to millions of single cells, and new technologies are on the horizon to increase to tens of millions of cells and above. Results In this work, we present the Inferelator 3.0, which has been significantly updated to integrate data from distinct cell types to learn context-specific regulatory networks and aggregate them into a shared regulatory network, while retaining the functionality of the previous versions. The Inferelator is able to integrate the largest single-cell datasets and learn cell-type specific gene regulatory networks. Compared to other network inference methods, the Inferelator learns new and informative Saccharomyces cerevisiae networks from single-cell gene expression data, measured by recovery of a known gold standard. We demonstrate its scaling capabilities by learning networks for multiple distinct neuronal and glial cell types in the developing Mus musculus brain at E18 from a large (1.3 million) single-cell gene expression dataset with paired single-cell chromatin accessibility data. Availability The inferelator software is available on GitHub (https://github.com/flatironinstitute/inferelator) under the MIT license and has been released as python packages with associated documentation (https://inferelator.readthedocs.io/). Supplementary information Supplementary data are available at Bioinformatics online.

SUMMARY Large-scale inference of eukaryotic transcription-regulatory networks remains challenging. One underlying reason is that existing algorithms typically ignore crucial regulatory mechanisms, such as RNA degradation and post-transcriptional processing. Here, we describe InfereCLaDR, which incorporates such elements and advances prediction in Saccharomyces cerevisiae. First, InfereCLaDR employs a high-quality Gold Standard dataset that we use separately as prior information and for model validation. Second, InfereCLaDR explicitly models transcription factor activity and RNA half-lives. Third, it introduces expression subspaces to derive condition-responsive regulatory networks for every gene. InfereCLaDR’s final network is validated by known data and trends and results in multiple insights. For example, it predicts long half-lives for transcripts of the nucleic acid metabolism genes and members of the cytosolic chaperonin complex as targets of the proteasome regulator Rpn4p. InfereCLaDR demonstrates that more biophysically realistic modeling of regulatory networks advances prediction accuracy both in eukaryotes and prokaryotes.

The gut microbiome is now widely recognized as a dynamic ecosystem that plays an important role in health and disease1. While current sequencing technologies make it possible to estimate relative abundances of host-associated bacteria over time2, 3, the biological processes governing their dynamics remain poorly understood. Therefore, as in other ecological systems4, 5, it is important to identify quantitative relationships describing global aspects of gut microbiota dynamics. Here we use multiple high-resolution time series data obtained from humans and mice6–8 to demonstrate that despite their inherent complexity, gut microbiota dynamics can be characterized by several robust scaling relationships. Interestingly, these patterns are highly similar to those previously observed across diverse ecological communities and economic systems, including the temporal fluctuations of animal and plant populations9–12 and the performance of publicly traded companies13. Specifically, we find power law relationships describing short- and long-term changes in gut microbiota abundances, species residence and return times, and the connection between the mean and variance of species abundances. The observed scaling relationships are altered in mice receiving different diets and affected by context-specific perturbations in humans. We use these macroecological relationships to reveal specific bacterial taxa whose dynamics are significantly affected by dietary and environmental changes. Overall, our results suggest that a quantitative macroecological framework will be important for characterizing and understanding complex dynamics of microbial communities.

Gene regulatory networks define regulatory relationships between transcription factors and target genes within a biological system, and reconstructing them is essential for understanding cellular growth and function. In this work, we present the Inferelator 3.0, which has been significantly updated to integrate data from distinct cell types to learn context-specific regulatory networks and aggregate them into a shared regulatory network, while retaining the functionality of the previous versions. The Inferelator 3.0 reliably learns informative networks from the model organisms Bacillus subtilis and Saccharomyces cerevisiae. We demonstrate its capabilities by learning networks for multiple distinct neuronal and glial cell types in the developing Mus musculus brain at E18 from a large (1.3 million) single-cell gene expression data set with paired single-cell chromatin accessibility data.