Longitudinal microbiome data sets are being generated with increasing regularity, and there is broad recognition that these studies are critical for unlocking the mechanisms through which the microbiome impacts human health and disease. However, there is a dearth of computational tools for analyzing microbiome time-series data. To address this gap, we developed an open-source software package, Microbiome Differentiable Interpretable Temporal Rule Engine (MDITRE), which implements a new highly efficient method leveraging deep-learning technologies to derive human-interpretable rules that predict host status from longitudinal microbiome data. Using semi-synthetic and a large compendium of publicly available 16S rRNA amplicon and metagenomics sequencing data sets, we demonstrate that in almost all cases, MDITRE performs on par with or better than popular uninterpretable machine learning methods, and orders-of-magnitude faster than the prior interpretable technique. MDITRE also provides a graphical user interface, which we show through case studies can be used to derive biologically meaningful interpretations linking patterns of microbiome changes over time with host phenotypes.
Graduate Students
I am always excited to work with talented graduate students with interests relevant to my lab, which focuses on developing novel machine learning/computational biology/wet lab approaches to further understanding of the microbiome–the trillions of microbes living on and within us. This fascinating, complex and dynamic ecosystem is crucial for human health, and when disrupted may contribute to a variety of diseases including infections, arthritis, allergies, cancer, heart and bowel disorders.
In general, I can only be a primary advisor (and provide financial support) for students enrolled at Harvard or MIT. However, I am open to co-advising students at other institutions.
If you’re interested, email me at ggerber#bwh.harvard.edu. Please include your CV and a brief description of your research interests.
Students should have a high level of interest in:
- Developing and applying new technologies to biomedical problems.
- Advancing knowledge of the microbiome and its role in human health and disease.
- Having your work make an impact on healthcare outcomes.
- Working on an interdisciplinary team and collaborating with computational, wet lab and clinical scientists.
About the lab: the Gerber Lab develops novel statistical machine learning models and high-throughput experimental systems to understand the role of the microbiota in human diseases, and applies these findings to develop new diagnostic tests and therapies. A particular focus of the Gerber Lab is understanding dynamic behaviors of host-microbial ecosystems. Our work in this area includes Bayesian statistical machine learning methods for discovering temporal patterns in microbiome data, inferring dynamical systems models from microbiome time-series data, or predicting host status from microbiome time-series data with human interpretable rules. We have applied these methods to a number of clinically relevant questions including understanding dynamic effects of antibiotics, infections and dietary changes on the microbiome, and designing bacteriotherapies for C. difficile infection and food allergy. We also apply our methods to synthetic biology problems, to engineer consortia of bacteria for diagnostic and therapeutic purposes.
Environment: the Gerber Lab is located in the Division of Computational Pathology, which Dr. Gerber heads, at Brigham and Women’s Hospital (BWH) at Harvard Medical School (HMS), and the Massachusetts Host-Microbiome Center, which Dr. Gerber co-directs. BWH, an HMS affiliated teaching hospital is adjacent to the HMS main quad and is the second largest non-university recipient of NIH research funding. The broad mandate of the BWH Division of Computational Pathology is to develop and apply advanced computational methods for furthering the understanding, diagnosis and treatment of human diseases. The Division is situated within the BWH Department of Pathology, which houses over 40+ established investigators, 50+ postdoctoral research fellows, and 100+ research support staff. In addition, BWH is part of the greater Longwood Medical Area in Boston, a rich, stimulating environment conducive to intellectual development and research collaborations, which includes HMS, Harvard School of Public Health, Boston Children’s Hospital and the Dana Farber Cancer Institute.
Postdoctoral Fellow, Deep Learning for Microbiome
Post-doctoral positions available (with flexible start dates) to develop novel deep learning approaches to further understanding of the microbiome–the trillions of microbes living on and within us. This fascinating, complex and dynamic ecosystem is crucial for human health, and when disrupted may contribute to a variety of diseases including infections, arthritis, allergies, cancer, heart and bowel disorders. Over the past decade, sequencing and other high-throughput methods have provided data about the microbiome at unprecedented scale.
We are looking for talented and highly motivated post-docs with strong mathematical backgrounds (computer science, computational biology, statistics, mathematics, ecology, physics, etc.) who want to develop and apply novel deep learning methods that will further understanding of the microbiome. Applications include forecasting microbial population dynamics in the gut for rational design of therapies, predicting the impact of the microbiome on the onset or progression of human diseases, predicting interactions with the host immune system, elucidating host-microbial metabolic interactions, and discovering functions of uncharacterized microbial metabolites and proteins. From the machine learning perspective, areas of interest include:
- Fully-differentiable interpretable probabilistic models based on relaxations and variational inference
- Deep Bayesian, dynamical systems and other structured models
- Neural topic models
- Deep learning models using sequence information
The position could be a good fit for either someone with a strong machine learning background who wants to get domain-specific research experience, OR someone with a strong mathematical background who wants to get more machine learning experience.
Applicants should have a high level of interest in:
- Applying new deep learning technologies to biomedical problems.
- Advancing knowledge of the microbiome and its role in human health and disease.
- Having your work make an impact on healthcare outcomes.
- Working on an interdisciplinary team and collaborating with computational, wet lab and clinical scientists.
The candidate is expected to engage with the broader machine learning and computational biology communities by presenting work at top conferences, as well as publishing applications of new methods in high impact journals. Although some experience modeling biological or other complex systems is required, microbiome specific knowledge is not required.
About the lab: the Gerber Lab develops novel statistical machine learning models and high-throughput experimental systems to understand the role of the microbiota in human diseases, and applies these findings to develop new diagnostic tests and therapies. A particular focus of the Gerber Lab is understanding dynamic behaviors of host-microbial ecosystems. Our work in this area includes Bayesian statistical machine learning methods for discovering temporal patterns in microbiome data, inferring dynamical systems models from microbiome time-series data, or predicting host status from microbiome time-series data with human interpretable rules. We have applied these methods to a number of clinically relevant questions including understanding dynamic effects of antibiotics, infections and dietary changes on the microbiome, and designing bacteriotherapies for C. difficile infection and food allergy. We also apply our methods to synthetic biology problems, to engineer consortia of bacteria for diagnostic and therapeutic purposes.
Environment: the Gerber Lab is located in the Division of Computational Pathology, which Dr. Gerber heads, at Brigham and Women’s Hospital (BWH) at Harvard Medical School (HMS), and the Massachusetts Host-Microbiome Center, which Dr. Gerber co-directs. BWH, an HMS affiliated teaching hospital is adjacent to the HMS main quad and is the second largest non-university recipient of NIH research funding. The broad mandate of the BWH Division of Computational Pathology is to develop and apply advanced computational methods for furthering the understanding, diagnosis and treatment of human diseases. The Division is situated within the BWH Department of Pathology, which houses over 40+ established investigators, 50+ postdoctoral research fellows, and 100+ research support staff. In addition, BWH is part of the greater Longwood Medical Area in Boston, a rich, stimulating environment conducive to intellectual development and research collaborations, which includes HMS, Harvard School of Public Health, Boston Children’s Hospital and the Dana Farber Cancer Institute.
Qualifications:
- PhD in computer science, computational biology, ecology, mathematics, physics, statistics, or other quantitative discipline.
- Excellent publication track record.
- Strong mathematical background with track record developing novel models and methods.
- Solid programming skills in Python, with PyTorch experience desirable.
- Experience modeling biological or other complex systems required; microbiome experience desirable, but not required.
- Superior communication skills and ability to work on multidisciplinary teams.
Email single PDF including cover letter, CV, unofficial transcripts, brief research statement and list of at least three references to Dr. Georg Gerber (ggerber@bwh.harvard.edu). In your CV, indicate whether you are a U.S. citizen/permanent resident or visa holder (and list visa type).
We are an equal opportunity employer and all qualified applicants will receive consideration for employment without regard to race, color, religion, sex, national origin, disability status, protected veteran status, gender identity, sexual orientation, pregnancy and pregnancy-related conditions or any other characteristic protected by law.
Research Scientist, Machine Learning for Microbiome
The Microbiome AI/Deep Learning Lab in the Massachusetts Host-Microbiome Center and Division of Computational Pathology at Brigham and Women’s Hospital/Harvard Medical School is seeking a scientist with experience in machine learning.
You will develop, deploy, and apply machine learning approaches, with a special emphasis on deep learning, to a variety of microbiology data sources. Applications will include forecasting microbial population dynamics in the gut, predicting impact of the microbiome on host phenotype, tracking infections in human populations, elucidating microbial metabolism, and discovering functions of uncharacterized microbial metabolites and proteins. An important component of the position will also include engagement with the broader research community to identify new application areas.
Applicants should have a high level of interest in:
- Applying new deep learning technologies to biomedical problems.
- Advancing knowledge of the microbiome and its role in human health and disease.
- Having your work make a direct impact on healthcare outcomes.
- Working on an interdisciplinary team and collaborating with computational, wet lab and clinical scientists.
- Engaging with the broader research community to advance applications of AI/deep learning for the microbiome.
About the environment: The Microbiome AI/Deep Learning Lab is a newly established initiative within the Massachusetts Host-Microbiome Center (MHMC) and the Division of Computational Pathology (DCP) at Brigham and Women’s Hospital (BWH)/Harvard Medical School (HMS). With recent funding from the Massachusetts Life Sciences Center, the Lab is building a state-of-the-art compute cluster with extensive GPU and CPU nodes, with the objective of making advanced deep learning technologies broadly available to microbiome researchers. The MHMC is a research and core facility that has worked with 100+ groups in the US and internationally to promote understanding of host-microbiome interactions in health and disease, emphasizing a focus on function to define causative effects of the microbiota and to harness this knowledge in developing new therapies, diagnostics and further commercial applications. The DCP is a research division with a broad mandate to develop and apply advanced computational methods for furthering the understanding, diagnosis and treatment of human diseases. BWH is an HMS affiliated teaching hospital, adjacent to the HMS main quad, and the second largest non-university recipient of NIH research funding.
Required Qualifications:
- PhD in Computational Biology, Computer Science, Physics, Statistics, Quantitative Microbial Genetics, Quantitative Ecology, or related quantitative discipline, with demonstrated experience in machine learning.
- Strong publication track record.
- Programming experience in Python.
- Experience with Unix, shell scripting, and high-performance computing environments (e.g., SLURM/LSF).
- Experience with bioinformatics methods and pipelines for next generation sequencing data analysis.
- Experience with organizing and managing large multi-omics datasets.
- Strong written and oral communication skills.
Desired Qualifications:
- Experience with PyTorch.
- Experience with microbiology/microbiome applications and metabolic modeling tools.
Email single PDF including cover letter, CV, and list of at least three references to Dr. Georg Gerber (ggerber#bwh.harvard.edu). In your CV, indicate whether you are a U.S. citizen/permanent resident or visa holder (and list visa type).
We are an equal opportunity employer and all qualified applicants will receive consideration for employment without regard to race, color, religion, sex, national origin, disability status, protected veteran status, gender identity, sexual orientation, pregnancy and pregnancy-related conditions or any other characteristic protected by law.
Gerber lab study showing gut metabolites predict C. diff recurrence
Clostridioides difficile infection (CDI) is the most common hospital acquired infection in the USA, with recurrence rates > 15%. Although primary CDI has been extensively linked to gut microbial dysbiosis, less is known about the factors that promote or mitigate recurrence. Using broad metabolomics data and statistics and machine learning models, Jen Dawkins, a HST PhD student and member of the Gerber lab, showed the metabolites in the gut can accurately predict C. difficile recurrence. These findings have implications for development of diagnostic tests and treatments that could ultimately short-circuit the cycle of CDI recurrence, by providing candidate metabolic biomarkers for diagnostics development, as well as offering insights into the complex microbial and metabolic alterations that are protective or permissive for recurrence.
The Massachusetts Lab for Artificial Intelligence/Deep Learning for the Microbiome
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.
$2.9M grant from the National Science Foundation “The rules of microbiota colonization of the mammalian gut”
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.
- PI: Georg K Gerber
- Co-PI: Harris Wang
- Co-I: Travis Gibson
