Biology subjects

Zeira, R.

Publications and source records attributed to Zeira, R..

4 recordsLinked to original sources

bioRxiv2024

HIPI: Spatially Resolved Multiplexed Protein Expression Inferred from H&E WSIs

Solid tumors are characterized by complex interactions between the tumor, the immune system and the microenvironment. These interactions and intra-tumor variations have both diagnostic and prognostic significance and implications. However, quantifying the underlying processes in patient samples requires expensive and complicated molecular experiments. In contrast, H&E staining is typically performed as part of the routine standard process, and is very cheap. Here we present HIPI (H&E Image Interpretation and Protein Expression Inference) for predicting cell marker expression from tumor H&E images. We process paired H&E and CyCIF images taken from serial sections of colorectal cancers to train our model. We show that our model accurately predicts the spatial distribution of several important cell markers, on both held-out tumor regions as well as new tumor samples taken from different patients. Moreover, using only the tissue image morphology, HIPI is able to colocalize the interactions between different cell types, further demonstrating its potential clinical significance.

bioinformatics↗

bioRxiv2023

PASTE2: Partial Alignment of Multi-slice Spatially Resolved Transcriptomics Data

Spatially resolved transcriptomics (SRT) technologies measure mRNA expression at thousands of locations in a tissue slice. However, nearly all SRT technologies measure expression in two dimensional slices extracted from a three-dimensional tissue, thus losing information that is shared across multiple slices from the same tissue. Integrating SRT data across multiple slices can help recover this information and improve downstream expression analyses, but multi-slice alignment and integration remains a challenging task. Existing methods for integrating SRT data either do not use spatial information or assume that the morphology of the tissue is largely preserved across slices, an assumption that is often violated due to biological or technical reasons. We introduce PASTE2, a method for partial alignment and 3D reconstruction of multi-slice SRT datasets, allowing only partial overlap between aligned slices and/or slice-specific cell types. PASTE2 formulates a novel partial Fused Gromov-Wasserstein Optimal Transport problem, which we solve using a conditional gradient algorithm. PASTE2 includes a model selection procedure to estimate the fraction of overlap between slices, and optionally uses information from histological images that accompany some SRT experiments. We show on both simulated and real data that PASTE2 obtains more accurate alignments than existing methods. We further use PASTE2 to reconstruct a 3D map of gene expression in a Drosophila embryo from a 16 slice Stereo-seq dataset. PASTE2 produces accurate alignments of multi-slice datasets from multiple SRT technologies, enabling detailed studies of spatial gene expression across a wide range of biological applications. Code availabilitySoftware is available at https://github.com/raphael-group/paste2

bioinformatics↗

bioRxiv2021

Alignment and Integration of Spatial Transcriptomics Data

Spatial transcriptomics (ST) is a new technology that measures mRNA expression across thousands of spots on a tissue slice, while preserving information about the spatial location of spots. ST is typically applied to several replicates from adjacent slices of a tissue. However, existing methods to analyze ST data do not take full advantage of the similarity in both gene expression and spatial organization across these replicates. We introduce a new method PASTE (Probabilistic Alignment of ST Experiments) to align and integrate ST data across adjacent tissue slices leveraging both transcriptional similarity and spatial distances between spots. First, we formalize and solve the problem of pairwise alignment of ST data from adjacent tissue slices, or layers, using Fused Gromov-Wasserstein Optimal Transport (FGW-OT), which accounts for variability in the composition and spatial location of the spots on each layer. From these pairwise alignments, we construct a 3D representation of the tissue. Next, we introduce the problem of simultaneous alignment and integration of multiple ST layers into a single layer with a low rank gene expression matrix. We derive an algorithm to solve the problem by alternating between solving FGW-OT instances and solving a Non-negative Matrix Factorization (NMF) of a weighted expression matrix. We show on both simulated and real ST datasets that PASTE accurately aligns spots across adjacent layers and accurately estimates a consensus expression matrix from multiple ST layers. PASTE outperforms integration methods that rely solely on either transcriptional similarity or spatial similarity, demonstrating the advantages of combining both types of information. Code availabilitySoftware is available at https://github.com/raphael-group/paste

bioinformatics↗

bioRxiv2020

STARCH: Copy number and clone inference from spatial transcriptomics data

Tumors are highly heterogeneous, consisting of cell populations with both transcriptional and genetic diversity. These diverse cell populations are spatially organized within a tumor, creating a distinct tumor microenvironment. A new technology called spatial transcriptomics can measure spatial patterns of gene expression within a tissue by sequencing RNA transcripts from a grid of spots, each containing a small number of cells. In tumor cells, these gene expression patterns represent the combined contribution of regulatory mechanisms, which alter the rate at which a gene is transcribed, and genetic diversity, particularly copy number aberrations (CNAs) which alter the number of copies of a gene in the genome. CNAs are common in tumors and often promote cancer growth through upregulation of oncogenes or downregulation of tumor-suppressor genes. We introduce a new method STARCH (Spatial Transcriptomics Algorithm Reconstructing Copy-number Heterogeneity) to infer CNAs from spatial transcriptomics data. STARCH overcomes challenges in inferring CNAs from RNA-sequencing data by leveraging the observation that cells located nearby in a tumor are likely to share similar CNAs. We find that STARCH outperforms existing methods for inferring CNAs from RNA-sequencing data without incorporating spatial information.

bioinformatics↗