Organ Fibrosis Collaboration (Saez-Rodriguez Lab)
Overview
Integrate the dismech knowledge base with the cross-organ fibrosis atlas from the Saez-Rodriguez lab (Heidelberg / EMBL-EBI), an open single-cell resource mapping shared and organ-specific fibrotic gene programs across heart, liver, kidney, and lung.
The atlas provides quantitative molecular data (gene signatures, TF activities, cell-cell communication, fibroblast subpopulations) while dismech provides structured, evidence-backed disease mechanism context (causal chains, phenotypes, treatments, clinical trials). The two are complementary: the atlas answers "what changes?" and dismech answers "why it matters clinically."
The Organ Fibrosis Atlas
Resource: https://organfibrosis.saezlab.org/ Preprint: Küchenhoff, Kim, Lanzer, Kretzler, Ramirez Flores & Saez-Rodriguez. "Shared and organ-specific gene expression programs of fibrotic diseases." bioRxiv 2026.03.09.709232v1. Code: https://github.com/saezlab/organfibrosis License: CC-BY-NC 4.0 (data), GPL-3.0 (code)
What it provides
| Aspect | Detail |
|---|---|
| Scale | >5 million cells, 20 studies, 25+ disease etiologies |
| Organs | Heart, liver, kidney, lung |
| Data type | Single-cell / single-nucleus RNA-seq meta-analysis |
| Key outputs | Cross-organ gene expression programs, disease fibroblast subpopulations with ECM signatures, organ-specific vs conserved TF activity profiles, intercellular communication patterns |
| Pipeline | Snakemake, standard scRNA-seq tooling (likely scanpy/decoupler/liana ecosystem) |
| Interactive | Dash-based web app for gene-of-interest queries across fibrotic tissues |
Related Saez lab resources
- Kidney fibrosis multi-omics model (GitHub): 14,000+ biomolecules across 7 time points post-TGF-β stimulation; temporal fibrosis marker discovery
- Liver disease atlas (GitHub): Cross-species (human/mouse) chronic liver disease transcriptomics
- ReHeaT (GitHub): Reference heart failure transcriptome
Existing dismech coverage
Disorders with explicit fibrotic mechanisms (21 files mention myofibroblasts/stellate cells)
| Disorder | Organ | Fibrosis mechanism |
|---|---|---|
| Liver Cirrhosis | Liver | HSC → myofibroblast transdifferentiation, collagen/ECM deposition |
| Primary Myelofibrosis | Bone marrow | TGF-β/PDGF/bFGF → reticulin/collagen deposition |
| Systemic Sclerosis | Skin, lung, heart, kidney | Multi-organ fibrosis via myofibroblast activation |
| Chronic Kidney Disease | Kidney | Tubulointerstitial fibrosis |
| Hepatitis B/C | Liver | Viral-driven hepatic fibrosis |
| Heart Failure | Heart | Cardiac fibrosis/remodeling |
| Dilated Cardiomyopathy | Heart | Myocardial fibrosis |
| Hypertensive Heart Disease | Heart | Pressure-overload cardiac fibrosis |
| Chronic Pancreatitis | Pancreas | Pancreatic stellate cell activation |
| Bird Fancier's Lung | Lung | Hypersensitivity pneumonitis → pulmonary fibrosis |
| IgG4-Related Disease | Multi-organ | Storiform fibrosis |
| Crohn Disease | GI tract | Intestinal stricturing/fibrosis |
| Polycystic Kidney Disease | Kidney | Cystic renal fibrosis |
| Cystic Fibrosis | Lung, pancreas, liver | Epithelial-driven (not fibroblast-centric) |
Broader fibrosis mentions
- 71 disorder files mention "fibrosis"
- 130 files mention TGF or collagen
- 68 files mention extracellular matrix
Key gap: no Idiopathic Pulmonary Fibrosis (IPF) entry
IPF is the prototypical fibrotic lung disease and a major focus of the organ fibrosis atlas. Creating this entry would be a high-value first deliverable.
Integration strategy
Value exchange
| dismech → Atlas | Atlas → dismech |
|---|---|
| Curated disease mechanisms with causal chains and PMID evidence | Quantitative gene signatures per cell type per organ |
| Ontology-grounded cell types (CL), processes (GO), genes (HGNC) | Disease fibroblast subpopulation definitions |
| Treatment-mechanism linkages (drug → target pathway → phenotype) | Cross-organ conserved vs organ-specific programs |
| Clinical trial connections to fibrotic phenotypes | TF activity profiles and intercellular communication data |
| Comorbidity trajectories between fibrotic diseases | Validated gene sets for computational model enrichment |
Alignment points
The dismech schema already supports everything needed for integration:
-
Cell types → CellTypeDescriptor with CL ontology. Atlas fibroblast subpopulations (e.g., ECM-producing disease fibroblasts) can be mapped to CL terms and added to pathophysiology entries.
-
Gene signatures → GeneDescriptor with HGNC. Cross-organ fibrosis genes identified by the atlas can populate
genesslots in pathophysiology entries. -
Biological processes → BiologicalProcessDescriptor with GO. Conserved fibrotic programs (ECM organization, TGF-β signaling, wound healing) already have GO terms.
-
Datasets → Dataset class with
SINGLE_CELL_RNA_SEQtype. Atlas study accessions (GEO/Zenodo) can be referenced directly. -
Computational models → ComputationalModel class. The Saez lab's multi-omics network models and TF activity inference could be represented.
-
Cross-organ comparison → The
comorbiditiesfield and Disease Trajectories integration can capture cross-organ fibrotic progression patterns.
Tasks
Tier 1: Low Effort (data annotation, new entries)
- [ ] Create IPF (Idiopathic Pulmonary Fibrosis) disorder entry — the archetypal fibrotic lung disease and central to the atlas
- [ ] Add Zenodo/GEO dataset references from the organ fibrosis atlas to existing entries (Liver Cirrhosis, Heart Failure, Dilated Cardiomyopathy, CKD)
- [ ] Enrich fibroblast/myofibroblast cell type descriptors in existing entries with CL terms for disease fibroblast subpopulations identified by the atlas
- [ ] Add cross-references between existing fibrotic disorders (comorbidities section) reflecting shared transcriptomic programs
Tier 2: Medium Effort (new entries, deeper annotation)
- [ ] Create NASH/MASLD entry — major liver fibrosis etiology covered by the atlas
- [ ] Create Diabetic Nephropathy entry — kidney fibrosis etiology covered by the atlas
- [ ] Enrich Heart Failure and Dilated Cardiomyopathy with cardiac fibrosis gene signatures from atlas
- [ ] Add conserved fibrotic TF activity profiles (TF → target gene → biological process chains) to pathophysiology entries
- [ ] Add intercellular communication patterns (e.g., fibroblast ↔ macrophage crosstalk) as pathophysiology mechanisms with cell_types and biological_processes
- [ ] Reference Saez lab kidney fibrosis multi-omics model as a ComputationalModel entry in CKD
Tier 3: High Effort (schema-level, cross-cutting)
- [ ] Define a "Conserved Fibrotic Response" shared pathophysiology module reusable across organ-specific entries (TGF-β activation → myofibroblast differentiation → ECM deposition → tissue stiffening)
- [ ] Add atlas-derived gene program annotations (co-expressed gene sets) — may need schema extension for GeneProgram class (synergy with VIRTUAL_CELL project)
- [ ] Integrate spatial transcriptomics data when atlas expands to spatial modality
- [ ] Cross-link fibrotic disease comorbidities with Disease Trajectories EHR data (synergy with COMORBIDITIES project)
Tier 4: Aspirational (collaborative research)
- [ ] Joint validation: use dismech causal chains to interpret atlas gene signatures (which genes fall on known mechanism paths?)
- [ ] Use atlas data to discover novel cell types involved in dismech-curated mechanisms
- [ ] Propose shared fibrosis mechanisms as drug targets: cross-reference atlas conserved programs with dismech treatment entries
- [ ] Contribute dismech disease-context annotations back to the atlas as structured metadata
- [ ] Explore MorPhiC iPSC perturbation data for fibrosis-relevant genes (ISL1 for cardiac, NKX2-1 for lung)
Cross-project synergies
| Project | Synergy |
|---|---|
| VIRTUAL_CELL | GeneProgram class needed for both; CELLxGENE datasets overlap with atlas source data; scGPT embeddings for fibroblast subpopulations |
| COMORBIDITIES | Cross-organ fibrotic progression (liver → cardiac, kidney → cardiac) informed by both EHR trajectories and atlas shared programs |
| GWAS_MECHANISMS | Fibrosis GWAS loci can be mapped to atlas cell-type-specific expression to assign mechanism context |
Contact / Collaboration
- PI: Julio Saez-Rodriguez (EMBL-EBI, saezrodriguez@ebi.ac.uk)
- First authors: Leonie Küchenhoff, Gahyun Kim (Heidelberg)
- Key collaborator: Matthias Kretzler (Michigan, kidney fibrosis expertise)
- Resource: https://organfibrosis.saezlab.org/
- Code: https://github.com/saezlab/organfibrosis
Notes
2026-03-12 (Project Creation)
Project created to explore collaboration with Saez-Rodriguez lab organ fibrosis atlas.
Key observations: 1. The preprint was posted March 9, 2026 — only 3 days ago. This is an ideal time to reach out for collaboration before publication. 2. dismech already has substantial fibrotic disease coverage (21 files with myofibroblast/stellate cell mechanisms, 71 files mentioning fibrosis). 3. The atlas covers 4 organs (heart, liver, kidney, lung) — dismech has entries for fibrotic diseases in all 4 but lacks IPF, the archetypal pulmonary fibrosis. 4. Schema is fully ready: CellTypeDescriptor, GeneDescriptor, Dataset (with scRNA-seq type), ComputationalModel all exist. No schema changes needed for Tier 1-2 work. 5. The Saez lab ecosystem (decoupler for TF/pathway activity, liana for cell-cell communication, liver disease atlas, ReHeaT) provides multiple integration points beyond the organ fibrosis atlas itself. 6. CC-BY-NC 4.0 license on the data is compatible with knowledge base annotation (citing/referencing, not redistributing raw data).