This work will leverage deep learning technologies to advance the microbiome field beyond finding associations in data, to accurately predicting the effects of perturbations on microbiota, elucidating mechanisms through which the microbiota affects the host, and improving bacteriotherapies to enable their success in the clinic. New deep learning models will be developed that address specific challenges for the microbiome, including noisy/small datasets, highly heterogenous human microbiomes, the need for direct interpretability of model outputs, complex multi-modal datasets, and constraints imposed by biological principles. Computational models and biological experiments will be directly coupled through reinforcing cycles of predicting, testing predictions with new experiments, and improving models. An important objective will also be to make computational tools widely available to the research community, through release of quality open-source software.
Through a $3.3M grant from the Massachusetts Life Science Center and in-kind support from Brigham and Women’s Hospital and Mass General Brigham, the BWH Massachusetts Host-Microbiome Center (MHMC) and Division of Computational Pathology will establish a new lab to develop and apply advanced AI/deep learning technologies to microbiome research. Dr. Georg Gerber, Chief of BWH Computational Pathology and co-director of the MHMC will head the new lab.
The microbiome is inherently complex and dynamic. Multi-omic data characterizing microbes in culture systems, animal models, and human populations can provide unique and complementary insights into these rich host-microbial ecosystems. However, to fully realize the potential of these data, sophisticated computational approaches are needed.
Artificial Intelligence (AI), and in particular Deep Learning (DL), are revolutionizing many fields, such as speech and image recognition. These technologies are also increasingly impacting the biomedical sciences.
The Lab aims to unleash the power of AI and DL technologies for the microbiome field.
Anchored by a dedicated large GPU with Tesla A100 nodes and CPU compute clusters, the Lab will develop custom AI/DL applications for the microbiome, deploy existing software in a managed and easy-to-use environment, and provide outreach and education to the microbiome community. The Lab will be staffed by principal investigators in the Division of Computational Pathology, as well as an application scientist and network engineers.
A joint initiative between the Brigham and Women’s Hospital (BWH) Division of Computational Pathology and the Massachusetts Host-Microbiome Center (MHMC), the Lab is funded by the Massachusetts Life Sciences Center and Brigham and Women’s Hospital/Mass General Brigham. Industry and academic users will be able to access the Lab through the MHMC’s existing core services model and through collaborations.
The Gerber lab in collaboration with the Wang lab at Columbia and the Gibson Lab at BWH and have received a $2.9M grant from the National Science Foundation to develop and apply novel computational and experimental methods to elucidate fundamental rules governing the formation and maintenance of complex microbial ecosystems in the mammalian gut.
Abstract: Microbiomes, or the collections of trillions of bacteria and other micro-organisms living on, within and around us, have enormous impact on human life. For example, they help people digest food, promote the growth of farm animals and crops, and degrade pollutants in the environment. Despite the importance of microbiomes, the processes governing their formation and maintenance remain poorly understood. The mammalian gut is a particularly intriguing system for microbiome studies, since a diverse collection of microbes has evolved that specifically colonizes and functions in that environment. The goal of the project is to derive fundamental rules that describe and predict the dynamic process of microbial colonization of the mammalian gut. To achieve this goal, the team of investigators will develop new computer-based methods to automatically extract predictive and explanatory rules from large microbiome data sets. The team will also develop new experimental tools and generate data sets in mouse measuring how microbiomes change over time and across space in the mammalian gut. Overall, the project will further the understanding of the formation of microbiomes in mammals and can provide broader insights into the emergence of other microbial ecosystems, such as those in soil and marine environments. These insights could ultimately help scientists to rationally alter or maintain microbiomes in different environments to benefit human activities. The project will also generate practical resources for the scientific community (computer-based tools and datasets) and provide education on the microbiome to college and elementary school students through courses and hands-on labs.
A wealth of genomic data provides information as to which microbes are present in environments, but little insight into underlying factors that explain or predict complex assemblages of microbial consortia. This project aims to elucidate mechanistic factors that drive the dynamic process of microbial colonization of the mammalian gut. These determinants will be investigated at multiple systems scales, from the level of microbial communities down to the level of individual genes. The project will leverage high-throughput experimental methods developed by the investigators, to generate data characterizing functional genetic selection and spatial organization of microbiota in the mammalian gut. From the Computer Science perspective, the project will develop new computational methods to infer human-interpretable rules and other structured outputs from complex and noisy high-throughput microbiome datasets, using Bayesian and neural-style approaches that incorporate prior biological knowledge while scaling to massive datasets. This project has three main thrusts: 1) Learn microbial community-level rules that quantitatively predict population dynamics of mouse gut colonization and assess these rules across differing ranges of microbial diversity and composition, 2) Elucidate microbial gene-level mechanisms that predict mouse gut colonization dynamics, and 3) Profile microbial spatiotemporal organization and dynamics during gut colonization at the species and gene level to predict microbial community dynamics. The project is expected to establish a set of new computational and experimental tools and principles for understanding the rules of microbial colonization of the gut, with potential applications to other ecosystems including gut microbiota of non-mammalian species as well as complex environmental microbiota.