October ABC Seminar: Weiruo Zhang, PhD, Stanford University

October ABC Seminar: Weiruo Zhang, PhD, Stanford University

Spatial biology is a new frontier that has become accessible through advances in spatial profiling technologies, such as multiplexed in situ imaging spatial proteomics, which can provide single-cell resolution up to 60 markers. In this talk, I will introduce a computational analysis pipeline that performs integrative analysis of spatial proteomics and single-cell RNA sequencing to identify clinically-relevant cellular interactions. The pipeline features (1) CELESTA, an unsupervised machine learning method for cell type identification in multiplexed spatial proteomics data; (2) a geospatial statistical method to identify cell-cell colocalizations; and (3) an integrative coupling of spatial proteomics and single-cell RNA sequencing data that identified cell-cell crosstalk associated with lymph node metastasis in head and neck cancer which we have validated through mouse model studies.

Research link:
https://profiles.stanford.edu/weiruo-zhang

Dr. Zhang is currently a Research Engineer at the Department of Biomedical Data Science and the Center for Cancer Systems Biology, Stanford School of Medicine. Dr. Zhang received her M.S. and Ph.D. in Electrical Engineering, both from Stanford University, with a focus on bioinformatics and developing computational algorithms for metabolomics data analysis. Her current research at Stanford primarily focuses on developing and implementing computational methods to integrate and analyze single-cell and spatial multi-omics data, such as single-cell RNA sequencing, spatial proteomics and spatial transcriptomics. Her research aims to apply quantitative approaches that bridge multi-omics, imaging, machine learning, and artificial intelligence to decipher biology for cancer progression and guide treatment responses.

 

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”

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

 

2023-24 ABC Seminar Speakers Announced

2023-24 ABC Seminar Speakers Announced

Developed by the Computational Pathology Department at Brigham and Women’s Hospital, the Advanced Biomedical Computation (ABC) Seminar, held monthly during the academic year, showcases innovative research from around the globe by up-and-coming investigators that are developing and applying advanced computational methods to solve biomedical problems.

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Mahmood receives 2023 Young Mentors Award from Harvard Medical School

Mahmood receives 2023 Young Mentors Award from Harvard Medical School

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

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

Jan. 30, 2023: Lambda Moses, California Institute of Technology

“From geospatial to spatial -omics with SpatialFeatureExperiment and Voyager”; https://partners.zoom.us/j/82826415806; To bring more of the geospatial tradition to spatial -omics, we developed SpatialFeatureExperiment (SFE), which extends the existing Bioconductor data structures SingleCellExperiment (SCE) and SpatialExperiment (SPE) with Simple Features to represent the geometries of Visium spots and cell segmentation and perform geometric operations. We developed the Voyager package that performs exploratory spatial data analysis (ESDA) on SFE objects.

Nov. 14, 2022: Martin Jankowiak, PhD, Broad Institute

“Inferring selection effects in SARS-CoV-2 with Bayesian Viral Allele Selection,” https://partners.zoom.us/j/86162386947; We develop Bayesian Viral Allele Selection (BVAS), a method that leverages the millions of SARS-CoV-2 viral genomes that have been sequenced across the globe to identify mutations linked to increased viral fitness.

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

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

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

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.