Biology subjects

Burlingame, E. A.

Publications and source records attributed to Burlingame, E. A..

7 recordsLinked to original sources

bioRxiv2021

A community-based approach to image analysis of cells, tissues and tumors

Emerging multiplexed imaging platforms provide an unprecedented view of an increasing number of molecular markers at subcellular resolution and the dynamic evolution of tumor cellular composition. As such, they are capable of elucidating cell-to-cell interactions within the tumor microenvironment that impact clinical outcome and therapeutic response. However, the rapid development of these platforms has far outpaced the computational methods for processing and analyzing the data they generate. While being technologically disparate, all imaging assays share many computational requirements for post-collection data processing. We convened a workshop to characterize these shared computational challenges and a follow-up hackathon to implement solutions for a selected subset of them. Here, we delineate these areas that reflect major axes of research within the field, including image registration, segmentation of cells and subcellular structures, and identification of cell types from their morphology. We further describe the logistical organization of these events, believing our lessons learned can aid others in uniting the imaging community around self-identified topics of mutual interest, in designing and implementing operational procedures to address those topics and in mitigating issues inherent in image analysis (e.g., sharing exemplar images of large datasets and disseminating baseline solutions to hackathon challenges through open-source code repositories).

bioinformatics↗

bioRxiv2021

Transfer Learning for Inference of Metastatic Origin from Whole Slide Histology

Accurate diagnosis of metastatic cancer is essential for prescribing optimal control strategies to halt further spread of metastasizing disease. While pathological inspection aided by immunohistochemistry staining provides a valuable gold standard for clinical diagnostics, deep learning methods have emerged as powerful tools for identifying clinically relevant features of whole slide histology relevant to a tumors metastatic origin. Although deep learning models require significant training data to learn effectively, transfer learning paradigms provide mechanisms to circumvent limited training data by first training a model on related data prior to fine-tuning on smaller data sets of interest. In this work we propose a transfer learning approach that trains a convolutional neural network to infer the metastatic origin of tumor tissue from whole slide images of hematoxylin and eosin (H&E) stained tissue sections and illustrate the advantages of pre-training network on whole slide images of primary tumor morphology. We further characterize statistical dissimilarity between primary and metastatic tumors of various indications on patch-level images to highlight limitations of our indication-specific transfer learning approach. Using a primary-to-metastatic transfer learning approach, we achieved mean class-specific areas under receiver operator characteristics curve (AUROC) of 0.779, which outperformed comparable models trained on only images of primary tumor (mean AUROC of 0.691) or trained on only images of metastatic tumor (mean AUROC of 0.675), supporting the use of large scale primary tumor imaging data in developing computer vision models to characterize metastatic origin of tumor lesions.

pathology↗

bioRxiv2020

Toward reproducible, scalable, and robust data analysis across multiplex tissue imaging platforms

The emergence of megascale single-cell multiplex tissue imaging (MTI) datasets necessitates reproducible, scalable, and robust tools for cell phenotyping and spatial analysis. We developed open-source, graphics processing unit (GPU)-accelerated tools for intensity normalization, phenotyping, and microenvironment characterization. We deploy the toolkit on a human breast cancer (BC) tissue microarray stained by cyclic immunofluorescence and benchmark our cell phenotypes against a published MTI dataset. Finally, we demonstrate an integrative analysis revealing BC subtype-specific features.

systems biology↗

bioRxiv2020

An Integrated Clinical, Omic, and Image Atlas of an Evolving Metastatic Breast Cancer

Mechanisms of therapeutic resistance manifest in metastatic cancers as tumor cell intrinsic alterations and extrinsic microenvironmental influences that can change during treatment. To support the development of methods for the identification of these mechanisms in individual patients, we present here an Omic and Multidimensional Spatial (OMS) Atlas generated from four serial biopsies of a metastatic breast cancer patient during 3.5 years of therapy. This resource links detailed, longitudinal clinical metadata including treatment times and doses, anatomic imaging, and blood-based response measurements to exploratory analytics including comprehensive DNA, RNA, and protein profiles, images of multiplexed immunostaining, and 2- and 3-dimensional scanning electron micrographs. These data reveal aspects of therapy-associated heterogeneity and evolution of the cancers genome, signaling pathways, immune microenvironment, cellular composition and organization, and ultrastructure. We present illustrative examples showing how integrative analyses of these data provide insights into potential mechanisms of response and resistance, and suggest novel therapeutic vulnerabilities.

cancer biology↗

bioRxiv2020

DISSECT: DISentangle SharablE ConTent for Multimodal Integration and Crosswise-mapping

Deep learning systems have emerged as powerful mechanisms for learning domain translation models. However, in many cases, complete information in one domain is assumed to be necessary for sufficient cross-domain prediction. In this work, we motivate a formal justification for domain-specific information separation in a simple linear case and illustrate that a self-supervised approach enables domain translation between data domains while filtering out domain-specific data features. We introduce a novel approach to identify domainspecific information from sets of unpaired measurements in complementary data domains by considering a deep learning cross-domain autoencoder architecture designed to learn shared latent representations of data while enabling domain translation. We introduce an orthogonal gate block designed to enforce orthogonality of input feature sets by explicitly removing non-sharable information specific to each domain and illustrate separability of domain-specific information on a toy dataset.

bioinformatics↗

bioRxiv2019

SHIFT: speedy histological-to-immunofluorescent translation of whole slide images enabled by deep learning

Spatially-resolved molecular profiling by immunostaining tissue sections is a key feature in cancer diagnosis, subtyping, and treatment, where it complements routine histopathological evaluation by clarifying tumor phenotypes. In this work, we present a deep learning-based method called speedy histological-to-immunofluorescent translation (SHIFT) which takes histologic images of hematoxylin and eosin-stained tissue as input, then in near-real time returns inferred virtual immunofluorescence (IF) images that accurately depict the underlying distribution of phenotypes without requiring immunostaining of the tissue being tested. We show that deep learning-extracted feature representations of histological images can guide representative sample selection, which improves SHIFT generalizability. SHIFT could serve as an efficient preliminary, auxiliary, or substitute for IF by delivering multiplexed virtual IF images for a fraction of the cost and in a fraction of the time required by nascent multiplexed imaging technologies.\n\nKEY POINTSO_LISpatially-resolved molecular profiling is an essential complement to histopathological evaluation of cancer tissues.\nC_LIO_LIInformation obtained by immunofluorescence imaging is encoded by features in histological images.\nC_LIO_LISHIFT leverages previously unappreciated features in histological images to facilitate virtual immunofluorescence staining.\nC_LIO_LIFeature representations of images guide sample selection, improving model generalizability.\nC_LI

systems biology↗

bioRxiv2019

Predicting Primary Site of Secondary Liver Cancer with a Neural Estimator of Metastatic Origin (NEMO)

Pathologists rely on clinical information, tissue morphology, and sophisticated molecular diagnostics to accurately infer the metastatic origin of secondary liver cancer. In this paper, we introduce a deep learning approach to identify spatially localized regions of cancerous tumor within hematoxylin and eosin stained tissue sections of liver cancer and to generate predictions of the cancers metastatic origin. Our approach achieves an accuracy of 90.2% when classifying metastatic origin of whole slide images into three distinct classes, which compares favorably to an established clinical benchmark by three board-certified pathologists whose accuracies ranged from 90.2% to 94.1% on the same prediction task. This approach illustrates the potential impact of deep learning systems to leverage morphological and structural features of H&E stained tissue sections to guide pathological and clinical determination of the metastatic origin of secondary liver cancers.

cancer biology↗