Gerber Lab awarded $3.1 Million Five Year NIH-NIGMS R35 Grant “Probabilistic deep learning models and integrated biological experiments for analyzing dynamic and heterogeneous microbiomes”

Gerber Lab awarded $3.1 Million Five Year NIH-NIGMS R35 Grant “Probabilistic deep learning models and integrated biological experiments for analyzing dynamic and heterogeneous microbiomes”

Posted on by Tarissa Arnold Mages

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.

RePORTER Link

 

Mahmood receives 2023 Young Mentors Award from Harvard Medical School

Mahmood receives 2023 Young Mentors Award from Harvard Medical School

Posted on by Tarissa Arnold Mages

Faisal Mahmood, PhD received the 2023 Young Mentor Award from Harvard Medical School for his outstanding contributions to mentorship.

The Young Mentor Award is one of several Excellence in Mentoring Awards that HMS established to recognize the value of quality mentoring relationships and the impact they have on the professional development and career advancement in medicine, teaching, research and administration. Created in 2005, the Young Mentor Award honors HMS faculty who are still in the early stages of their career but are devoting their time to providing mentoring for others.

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Mahmood Lab develops deep learning model for transforming tissue images: Nature Biomedical Engineering 2022

Mahmood Lab develops deep learning model for transforming tissue images: Nature Biomedical Engineering 2022

Posted on by Tarissa Arnold Mages

Histological artefacts in cryosectioned tissue can hinder rapid diagnostic assessments during surgery. Formalin-fixed and paraffin-embedded (FFPE) tissue provides higher quality slides, but the process for obtaining them is laborious (typically lasting 12–48 h) and hence unsuitable for intra-operative use. Here we report the development and performance of a deep-learning model that improves the quality of cryosectioned whole-slide images by transforming them into the style of whole-slide FFPE tissue within minutes. The model consists of a generative adversarial network incorporating an attention mechanism that rectifies cryosection artefacts and a self-regularization constraint between the cryosectioned and FFPE images for the preservation of clinically relevant features. Transformed FFPE-style images of gliomas and of non-small-cell lung cancers from a dataset independent from that used to train the model improved the rates of accurate tumour subtyping by pathologists.

Ozyoruk, K.B., Can, S., Darbaz, B. et al. A deep-learning model for transforming the style of tissue images from cryosectioned to formalin-fixed and paraffin-embedded. Nat. Biomed. Eng 6, 1407–1419 (2022). https://doi.org/10.1038/s41551-022-00952-9

Mahmood Lab develops self-supervised deep learning algorithm: Nature Biomedical Engineering 2022

Mahmood Lab develops self-supervised deep learning algorithm: Nature Biomedical Engineering 2022

Posted on by Tarissa Arnold Mages

The adoption of digital pathology has enabled the curation of large repositories of gigapixel whole-slide images (WSIs). Computationally identifying WSIs with similar morphologic features within large repositories without requiring supervised training can have significant applications. However, the retrieval speeds of algorithms for searching similar WSIs often scale with the repository size, which limits their clinical and research potential. Here we show that self-supervised deep learning can be leveraged to search for and retrieve WSIs at speeds that are independent of repository size. The algorithm, which we named SISH (for self-supervised image search for histology) and provide as an open-source package, requires only slide-level annotations for training, encodes WSIs into meaningful discrete latent representations and leverages a tree data structure for fast searching followed by an uncertainty-based ranking algorithm for WSI retrieval. We evaluated SISH on multiple tasks (including retrieval tasks based on tissue-patch queries) and on datasets spanning over 22,000 patient cases and 56 disease subtypes. SISH can also be used to aid the diagnosis of rare cancer types for which the number of available WSIs is often insufficient to train supervised deep-learning models.

Chen, C., Lu, M.Y., Williamson, D.F.K. et al. Fast and scalable search of whole-slide images via self-supervised deep learning. Nat. Biomed. Eng 6, 1420–1434 (2022). https://doi.org/10.1038/s41551-022-00929-8

Gerber Lab’s “MDITRE: Scalable and Interpretable Machine Learning for Predicting Host Status from Temporal Microbiome Dynamics” is mSystems Editor’s Pick

Gerber Lab’s “MDITRE: Scalable and Interpretable Machine Learning for Predicting Host Status from Temporal Microbiome Dynamics” is mSystems Editor’s Pick

Posted on by admin

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. 

Mahmood Lab’s Pan-cancer integrative histology-genomic analysis is featured on cover of Cancer Cell

Mahmood Lab’s Pan-cancer integrative histology-genomic analysis is featured on cover of Cancer Cell

Posted on by Tim Janicki

The rapidly emerging field of computational pathology has demonstrated promise in developing objective prognostic models from histology images. However, most prognostic models are either based on histology or genomics alone and do not address how these data sources can be integrated to develop joint image-omic prognostic models. Additionally, identifying explainable morphological and molecular descriptors from these models that govern such prognosis is of interest. We use multimodal deep learning to jointly examine pathology whole-slide images and molecular profile data from 14 cancer types. Our weakly supervised, multimodal deep-learning algorithm is able to fuse these heterogeneous modalities to predict outcomes and discover prognostic features that correlate with poor and favorable outcomes. We present all analyses for morphological and molecular correlates of patient prognosis across the 14 cancer types at both a disease and a patient level in an interactive open-access database to allow for further exploration, biomarker discovery, and feature assessment.

Chen RJ, Lu MY, Williamson DFK, Chen TY, Lipkova J, Noor Z, Shaban M, Shady M, Williams M, Joo B, Mahmood F. Pan-cancer integrative histology-genomic analysis via multimodal deep learning. Cancer Cell. 2022 Aug 8;40(8):865-878.e6. doi: 10.1016/j.ccell.2022.07.004. PMID: 35944502.

Graduate Students, Gerber Lab

Posted on by admin

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, Gerber Lab

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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.

Computational Biology (ML4Bio) Postdoctoral Fellow – Gibson Lab

Posted on by Travis Gibson

Opening for a Postdoctoral Research Fellow to join the Gibson Lab https://gibsonlab.io at Harvard Medical School and Brigham and Women’s Hospital. We leverage tools from machine learning and control theory to understand biological systems. Control theoretic concepts are integrated both in the design of our optimization schemes and statistical machine learning models, as well as in the design of our in vitro and in vivo experiments. Our main area of focus is the microbiome and microbial dynamics more specifically. Applications include the design of bacteriotherapies (bugs-as-drugs), developing methods to learn microbial dynamics at ecosystem-scale, studying the impact of phages on microbial communities, methods for tracking low abundance pathogens, and methods for integrating multiple data modalities and prior knowledge (from other studies or databases) in time-series models. We focus on Bayesian methods that propagate measurement uncertainty throughout the model so that we can access confidence in model parameters and to help prioritize follow-up experiments. ML techniques applied include variational inference, Bayesian non-parametric models, and relaxation techniques (for making discrete models differentiable).

The specific project(s) you will be working on will fall under one of the following grants. Follow the links below for more details:

The candidate will also be encouraged to design their own experiments as well, which would then be carried out by staff in the germ-free mouse facility or in a collaborating wet lab. In addition to addressing our biological questions we also include key experimental components that can aid in validating our methods that would otherwise not be included in a purely hypothesis driven experiment. For a candidate wanting some wet lab experience we are looking to develop new single-molecule enzyme-linked immunosorbent assays (digital ELISA) to measure low abundance host inflammatory markers in feces (please mention this explicitly in your cover letter if interested).

Qualifications

  • PhD in computer science, applied mathematics, ecology, computational biology, systems biology, 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; this isn’t a software engineering job, but you will need to be able to develop efficient implementations and apply your work to real biomedical data
  • Ability to reside in the U.S. and legally work in the country.

About the lab environment

The Gibson Lab is located in the Division of Computational Pathology at Brigham and Women’s Hospital (BWH), a Harvard Medical School teaching hospital, which is the second largest non-university recipient of NIH research funding. The broad mandate of the 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 the Harvard Medical School quad, Harvard School of Public Health, Boston Children’s Hospital, and the Dana Farber Cancer Institute. Many of our lab members also have appointments at the Massachusetts Institute of Technology and the Broad Institute.

Applications Process

Submit: (1) brief research statement (not to exceed 2 pages); (2) curriculum vitae; (3) two most relevant publications; (4) names and contact information of three individuals who can serve as references to: Travis Gibson, tegibson@bwh.harvard.edu. If you wish to chat briefly over Zoom before submitting materials to learn more details about our ongoing work, please inquire about this possibility.

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.

The Massachusetts Lab for Artificial Intelligence/Deep Learning for the Microbiome

The Massachusetts Lab for Artificial Intelligence/Deep Learning for the Microbiome

Posted on by admin

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.