Thor: a platform for cell-level investigation of spatial transcriptomics and histology [Heart Failure]

Spatial transcriptomics links gene expression with tissue morphology, however, current tools often prioritize genomic analysis, lacking integrated image interpretation. To address this, we present Thor, a comprehensive platform for cell-level analysis of spatial transcriptomics and histological images. Thor employs an anti-shrinking Markov diffusion method to infer single-cell spatial transcriptome from spot-level data, effectively combining gene expression and cell morphology. The platform includes 10 modular tools for genomic and image-based analysis, and is paired with Mjolnir, a web-based interface for interactive exploration of gigapixel images. Thor is validated on simulated data and multiple spatial platforms (ISH, MERFISH, Xenium, Stereo-seq). Thor identifies regenerative signatures in heart failure, unbiasedly screens breast cancer hallmarks, resolves fine layers in mouse olfactory bulb, and annotates fibrotic heart tissue. In high-resolution Visium HD data, it enhances spatial gene patterns aligned with histology. By bridging transcriptomic and histological analysis, Thor enables holistic tissue interpretation in spatial biology. Sample collection and preparation Tissues were collected from patients wearing LVAD before a heart transplant. All samples were obtained under an approved IRB protocol (Pro00006097:1 Congestive Heart Failure) at Houston Methodist Hospital. FFPE heart failure tissue samples were collected using standard-of-care procedures. Tissue sections (10 μm) obtained from the FFPE tissues were mounted on Visium spatial gene expression slides (10x Genomics, 1000520). The samples were processed as described in the manufacturer’s protocols. ST by 10x Genomics Visium The tissue slides were permeabilized at 37 °C for 6 min, and polyadenylated mRNA was captured by oligonucleotides bound to the slides. Reverse transcription, second-strand synthesis, complementary DNA (cDNA) amplification and library preparation proceeded using the Visium Spatial Gene Expression Slide & Reagent Kit (10x Genomics, 1000520) according to the manufacturer’s protocol. After evaluation by real-time PCR, cDNA amplification included 13-14 cycles. Indexed libraries were pooled equimolarly and sequenced on a NovaSeq X Plus instrument in a PE28/150 run (Illumina). An average of 26, 011 paired reads were generated per spot and the median genes per spot were 2,277. Tissues were stained with H&E, and slides were scanned on a Pannoramic MIDI scanner (3DHISTECH) using a ×20, 0.8-NA objective. *************************************************************** patient privacy, this data does not have fastq file ***************************************************************