The Digestive Disease Data Science Commons: Host Datasets

CSIBD investigators focus on a comprehensive approach for investigating the basis of human disease, going beyond massively parallel sequencing to dissect cellular circuitry in order to make functional genotype-phenotype connections. Studies are geared toward identifying the role of disease-linked functional variants in order to uncover therapeutic targets.

Raw data links will take you to public access (e.g. GEO, SRA) and protected (e.g. DUOS, dbGAP) repositories.  Please note that DUOS links in this page will direct you to the DUOS landing page.  Once you sign in to DUOS, you should arrive at the data library page in which you can use the search bar to look up the study you are interested in (e.g. search ‘000146’).  Like dbGAP, DUOS hosts protected clinical data and additional permissions are required for access as explained in their step by step tutorial.

Understanding disease at the single cell level

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  Spatially restricted immune and microbiota-driven adaptation of the gut

  Mayassi et al have created a blueprint of the gut by analyzing the entire mouse intestine, mapping gene expression and cell states and location both in the healthy gut an in response to perturbations such as circadian rhythm, changes in the microbiome, and inflammation.

  • Raw data

  • Explore the data

  • Code: GitLab and Zenodo

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  Human CD atlas study between colon and terminal ileum

  To characterize cell type-specific transcriptional heterogeneity in active Crohn's disease, Kong et al profiled 720,633 cells from terminal ileum and colon of 71 donors with varying inflammation status.

  • Raw data - 000145, 000146

  • Explore the data

  • Code

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  Intra- and inter-cellular rewiring of the human colon during ulcerative colitis

  To understand the cell type specificities and pathways of action of risk alleles for ulcerative colitis, Smillie et al generated an atlas of 366,650 cells from the colon mucosa of 18 UC patients and 12 healthy individuals

  • Raw data - 000110

  • Explore the data

  • Code

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  Adult Eosinophilic Esophagitis Registry Atlas

  Ding et al profiled more than 400,000 single cells from the esophageal mucosa of seven healthy and 15 eosinophilic esophagitis (EoE) participants. They found 60 cell subsets and changes in cell states, compositions, and interactions that reveal new features of EoE.

  • Raw data

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  • Code

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  Remodeling of colon plasma cell repertoire within ulcerative colitis patients

  This study characterizes the plasma cell and monoclonal antibody repertoire throughout the human colon at high resolution using matched single cell VDJ-and RNA-seq profiling, as well as antibody characterization of biopsies from patients with ulcerative colitis and healthy controls.

  • Raw data - 000148

  • Explore the data

  • Code

Featured: Bringing diversity into genetics

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  Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries

  Liu Z, Liu R, Gao H, Jung S, Gao X, Sun R, Liu X, Kim Y, Lee HS, Kawai Y, Nagasaki M, Umeno J, Tokunaga K, Kinouchi Y, Masamune A, Shi W, Shen C, Guo Z, Yuan K; FinnGen; International Inflammatory Bowel Disease Genetics Consortium; Chinese Inflammatory Bowel Disease Genetics Consortium; Zhu S, Li D, Liu J, Ge T, Cho J, Daly MJ, McGovern DPB, Ye BD, Song K, Kakuta Y, Li M, Huang H.

  In a study led by PFS award recipient Dr. Hailiang Huang, CSIBD investigators and collaborators created the first sizable sample of East Asian ancestries in studying IBD genetics. Eighty-one novel IBD associations were identified, including many new coding variants enriched in East Asian ancestries. These new coding variants deepen the IBD allelic series to facilitate target modulation in drug discoveries. The study also found that while IBD genetic effects are generally consistent across ancestries, genetics underlying CD appear more ancestral dependent than UC, driven by both allele frequency and genetic effect.

  Individual-level genotype data for EAS samples are available upon request: SHA1, Z.L. (zhanjuliu@tongji.edu.cn); KOR1, K.S. (kysong@amc.seoul.kr); JPN1, Y. Kakuta (ykakuta@med.tohoku.ac.jp) and; ICH1, IIBDGC (ibdgc-dcc@mssm.edu). Please note that access to individual-level genotypes from samples recruited within mainland China are subject to the policies and approvals from the Human Genetic Resource Administration, Ministry of Science and Technology of the People’s Republic of China.

  Data - CaVEMaN and DAP-G GTEx v8 Fine-Mapping cis-eQTL Data; 1000 Genomes Project Phase 3; TOPMed reference panel R2; Human Genome Diversity Project; Simons Genome Diversity Project; Korean Personal Genome Diversity Project; NBDC human database (accession ID: JGAS000114). 

  STRING functional protein association networks.

  NFE summary statistics; FIN summary statistics are from FinnGen R7; and more.

  PRS weights and genome-wide summary statistics for the meta-analyzed EAS samples, and across all study samples (EAS and EUR) can be downloaded here. 

CSIBD integrative studies

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  Mouse colon stroma inflammation

  Jasso et al performed single-cell RNA-sequencing of colon-derived stromal cells in mice and identified distinct classes of fibroblasts with gene signatures that are differentially regulated by chronic inflammation.

  • Raw data

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  • Code

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  The human and mouse enteric nervous system at single cell resolution

  Drokhlyansky, Smillie et al report on the development of methods to profile the ENS of adult mice and humans at single-cell resolution: RAISIN RNA-seq for profiling intact nuclei with ribosome-bound mRNA and MIRACL-seq for label-free enrichment of rare cell types by droplet-based profiling.

  • Raw data - 000119

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  • Code

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  B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV

  By analyzing samples from patients that recovered from COVID-19, Scheid et al characterize transcriptional differences among SARS-CoV-2-specific B cells. Their findings will inform design of immunogens to elicit cross-reactive protection.

  • Raw data:seq - 000125

  • Explore the data

  • Raw data:protein - 7M6D, 7M6E, 7M6F, 7M6G, 7M6H, and 7M6I

  • Raw data:electron microscopy - EMD-23694, EMD-23695, EMD-23696, EMD-23697, EMD-23698

  • Code

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  Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses

  Xu et al analyzed 58,067 immune cells from the mouse small intestine by single-cell RNA-seq (scRNA-seq), at steady-state and after induction of a type 2 inflammatory reaction to ovalbumin. The analysis revealed broad shifts in both cell-type composition and cell programs in response to the inflammation, especially in group 2 innate lymphoid cells (ILC2s)

  • Raw data

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  • Code

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  Genome-wide enhancer maps link risk variants to disease genes

  Nasser et al applied the activity-by-contact (ABC) model to build maps that connect enhancers to their target genes in 131 cell types and tissues. Using those maps, the team linked more than 5,000 GWAS signals to nearly 2,250 genes across 72 traits and diseases. The researchers also predicted which enhancers contain risk variants for inflammatory bowel disease, suggesting a possible disease mechanism.

  • Raw data:seq

  • UK Biobank fine-mapping data

  • ABC predictions

  • Code

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  A γδ T cell-IL-3 axis controls allergic responses through sensory neurons

  Flayer et al describe describe a T cell-IL-3 signaling axis that controls the allergen responsiveness of cutaneous sensory neurons

  • Raw data

  • Code

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  Single-cell transcriptomic analyses reveal distinct immune cell contributions to epithelial barrier dysfunction in checkpoint inhibitor colitis

  Immune checkpoint inhibitor treatments are limited by immune-related adverse events, including checkpoint inhibitor colitis (irColitis). Using single-cell multi-omics to profile ~300,000 cells from colon mucosa and blood of 13 patients with cancer who developed irColitis, Thomas et al found expansions in several T and inflammatory cell types, epithelial changes suggesting a breakdown of the mucosal barrier, and decreased intestinal absorption, as well as possible drug targets.

  • Raw data

  • Explore the data

  • Code - GitHub and Zenodo

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  Prediction of single-cell RNA expression profiles in live cells by Raman microscopy with Raman2RNA

  Kobayashi-Kirschvink et al developed Raman2RNA (R2R), an experimental and computational framework for inferring single-cell RNA expression profiles from label-free nondestructive Raman hyperspectral images.

  • Raw data

  • Code

  • Control software for Raman microscope

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  A genomic mutational constraint map using variation in 76,156 human genomes

  Chen et al presents Gnocchi (Genomic NOn-Coding Constraint of HaploInsufficient variation), a genomic constraint map for the whole genome. Gnocchi reveals patterns in how natural selection has shaped the human genome and could help clinical geneticists interpret non-coding variation in patients with rare diseases.

  • Aggregated allele frequency dataset

  • Code:QC

  • Code:functions

  • Code:statistics

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  Genetic vulnerability to Crohn's disease reveals a spatially resolved epithelial restitution program

  Nakata et al explored Crohn's disease risk variant HGFAC R509H, finding that it impairs mucosal healing and revealing a coordinated wound healing response mediated by wound-associated epithelial (WAE) cells and fibroblasts. The team used integrative spatial profiling methods to characterize the intercellular communication network through which WAE cells promote tissue healing.

  • Raw data

  • Code