Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy

Dataset overview

Participants 199

Samples 199

Reuse readiness 6.0/10 evidence-backed score

Single-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy.

Martin JC, Chang C, Boschetti G, Ungaro R, Giri M, Grout JA, Gettler K, Chuang LS, et al. · Cell · 2019

Abstract

Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single-cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities.

doi:10.1016/j.cell.2019.08.008 ↗ PMID 31474370 ↗ PMC7060942 ↗

Study facts

Organism: Homo sapiens
Platform: Illumina HiSeq 2000
Age group: paediatric
Disease groups: —
Anatomical sites: ileum

Data availability

Processed matrix

File types CSV

Ileal biopsy199

Accession	Sample	Tissue	Molecule
`GSM3975848`	Ileal biopsy, J10352	Ileal biopsy	total RNA
`GSM3975850`	Ileal biopsy, J10327	Ileal biopsy	total RNA
`GSM3975851`	Ileal biopsy, J10123	Ileal biopsy	total RNA
`GSM3975852`	Ileal biopsy, J10201	Ileal biopsy	total RNA
`GSM3975854`	Ileal biopsy, J10278	Ileal biopsy	total RNA
`GSM3975855`	Ileal biopsy, J10362	Ileal biopsy	total RNA
`GSM3975857`	Ileal biopsy, J10347	Ileal biopsy	total RNA
`GSM3975858`	Ileal biopsy, J10033	Ileal biopsy	total RNA
`GSM3975860`	Ileal biopsy, J10175	Ileal biopsy	total RNA
`GSM3975861`	Ileal biopsy, J10174	Ileal biopsy	total RNA
`GSM3975863`	Ileal biopsy, J10344	Ileal biopsy	total RNA
`GSM3975864`	Ileal biopsy, J10291	Ileal biopsy	total RNA
`GSM3975866`	Ileal biopsy, J10348	Ileal biopsy	total RNA
`GSM3975867`	Ileal biopsy, J10231	Ileal biopsy	total RNA
`GSM3975868`	Ileal biopsy, J10178	Ileal biopsy	total RNA
`GSM3975870`	Ileal biopsy, J10095	Ileal biopsy	total RNA
`GSM3975871`	Ileal biopsy, J10357	Ileal biopsy	total RNA
`GSM3975873`	Ileal biopsy, J10197	Ileal biopsy	total RNA
`GSM3975874`	Ileal biopsy, J10169	Ileal biopsy	total RNA
`GSM3975876`	Ileal biopsy, J10079	Ileal biopsy	total RNA
`GSM3975877`	Ileal biopsy, J10359	Ileal biopsy	total RNA
`GSM3975879`	Ileal biopsy, J10370	Ileal biopsy	total RNA
`GSM3975880`	Ileal biopsy, J10209	Ileal biopsy	total RNA
`GSM3975882`	Ileal biopsy, J10315	Ileal biopsy	total RNA
`GSM3975883`	Ileal biopsy, J10371	Ileal biopsy	total RNA
`GSM3975885`	Ileal biopsy, J10286	Ileal biopsy	total RNA
`GSM3975886`	Ileal biopsy, J10240	Ileal biopsy	total RNA
`GSM3975888`	Ileal biopsy, J10386	Ileal biopsy	total RNA
`GSM3975889`	Ileal biopsy, J10051	Ileal biopsy	total RNA
`GSM3975891`	Ileal biopsy, J10014	Ileal biopsy	total RNA
`GSM3975892`	Ileal biopsy, J10369	Ileal biopsy	total RNA
`GSM3975894`	Ileal biopsy, J10380	Ileal biopsy	total RNA
`GSM3975895`	Ileal biopsy, J10026	Ileal biopsy	total RNA
`GSM3975896`	Ileal biopsy, J10055	Ileal biopsy	total RNA
`GSM3975898`	Ileal biopsy, J10120	Ileal biopsy	total RNA
`GSM3975899`	Ileal biopsy, J10288	Ileal biopsy	total RNA
`GSM3975901`	Ileal biopsy, J10136	Ileal biopsy	total RNA
`GSM3975902`	Ileal biopsy, J10057	Ileal biopsy	total RNA
`GSM3975904`	Ileal biopsy, J10140	Ileal biopsy	total RNA
`GSM3975905`	Ileal biopsy, J10255	Ileal biopsy	total RNA
`GSM3975907`	Ileal biopsy, J10114	Ileal biopsy	total RNA
`GSM3975908`	Ileal biopsy, J10329	Ileal biopsy	total RNA
`GSM3975910`	Ileal biopsy, J10018	Ileal biopsy	total RNA
`GSM3975911`	Ileal biopsy, J10163	Ileal biopsy	total RNA
`GSM3975913`	Ileal biopsy, J10118	Ileal biopsy	total RNA
`GSM3975915`	Ileal biopsy, J10127	Ileal biopsy	total RNA
`GSM3975916`	Ileal biopsy, J10062	Ileal biopsy	total RNA
`GSM3975917`	Ileal biopsy, J10129	Ileal biopsy	total RNA
`GSM3975919`	Ileal biopsy, J10280	Ileal biopsy	total RNA
`GSM3975920`	Ileal biopsy, J10170	Ileal biopsy	total RNA
`GSM3975922`	Ileal biopsy, J10097	Ileal biopsy	total RNA
`GSM3975923`	Ileal biopsy, J10070	Ileal biopsy	total RNA
`GSM3975925`	Ileal biopsy, J10035	Ileal biopsy	total RNA
`GSM3975926`	Ileal biopsy, J10396	Ileal biopsy	total RNA
`GSM3975928`	Ileal biopsy, J10238	Ileal biopsy	total RNA
`GSM3975929`	Ileal biopsy, J10403	Ileal biopsy	total RNA
`GSM3975931`	Ileal biopsy, J10409	Ileal biopsy	total RNA
`GSM3975932`	Ileal biopsy, J10393	Ileal biopsy	total RNA
`GSM3975934`	Ileal biopsy, J10016	Ileal biopsy	total RNA
`GSM3975935`	Ileal biopsy, J10053	Ileal biopsy	total RNA
`GSM3975937`	Ileal biopsy, J10385	Ileal biopsy	total RNA
`GSM3975938`	Ileal biopsy, J10098	Ileal biopsy	total RNA
`GSM3975939`	Ileal biopsy, J10125	Ileal biopsy	total RNA
`GSM3975941`	Ileal biopsy, J10072	Ileal biopsy	total RNA
`GSM3975942`	Ileal biopsy, J10196	Ileal biopsy	total RNA
`GSM3975944`	Ileal biopsy, J10253	Ileal biopsy	total RNA
`GSM3975945`	Ileal biopsy, J10308	Ileal biopsy	total RNA
`GSM3975947`	Ileal biopsy, J10404	Ileal biopsy	total RNA
`GSM3975948`	Ileal biopsy, J10346	Ileal biopsy	total RNA
`GSM3975950`	Ileal biopsy, J10252	Ileal biopsy	total RNA
`GSM3975951`	Ileal biopsy, J10258	Ileal biopsy	total RNA
`GSM3975953`	Ileal biopsy, J10275	Ileal biopsy	total RNA
`GSM3975954`	Ileal biopsy, J10294	Ileal biopsy	total RNA
`GSM3975956`	Ileal biopsy, J10183	Ileal biopsy	total RNA
`GSM3975957`	Ileal biopsy, J10332	Ileal biopsy	total RNA
`GSM3975959`	Ileal biopsy, J10269	Ileal biopsy	total RNA
`GSM3975960`	Ileal biopsy, J10173	Ileal biopsy	total RNA
`GSM3975961`	Ileal biopsy, J10092	Ileal biopsy	total RNA
`GSM3975963`	Ileal biopsy, J10086	Ileal biopsy	total RNA
`GSM3975964`	Ileal biopsy, J10135	Ileal biopsy	total RNA
`GSM3975966`	Ileal biopsy, J10063	Ileal biopsy	total RNA
`GSM3975967`	Ileal biopsy, J10065	Ileal biopsy	total RNA
`GSM3975969`	Ileal biopsy, J10374	Ileal biopsy	total RNA
`GSM3975970`	Ileal biopsy, J10153	Ileal biopsy	total RNA
`GSM3975972`	Ileal biopsy, J10121	Ileal biopsy	total RNA
`GSM3975973`	Ileal biopsy, J10283	Ileal biopsy	total RNA
`GSM3975974`	Ileal biopsy, J10265	Ileal biopsy	total RNA
`GSM3975976`	Ileal biopsy, J10119	Ileal biopsy	total RNA
`GSM3975977`	Ileal biopsy, J10004	Ileal biopsy	total RNA
`GSM3975979`	Ileal biopsy, J10143	Ileal biopsy	total RNA
`GSM3975980`	Ileal biopsy, J10325	Ileal biopsy	total RNA
`GSM3975982`	Ileal biopsy, J10377	Ileal biopsy	total RNA
`GSM3975983`	Ileal biopsy, J10206	Ileal biopsy	total RNA
`GSM3975985`	Ileal biopsy, J10273	Ileal biopsy	total RNA
`GSM3975986`	Ileal biopsy, J10059	Ileal biopsy	total RNA
`GSM3975987`	Ileal biopsy, J10402	Ileal biopsy	total RNA
`GSM3975989`	Ileal biopsy, J10241	Ileal biopsy	total RNA
`GSM3975990`	Ileal biopsy, J10090	Ileal biopsy	total RNA
`GSM3975992`	Ileal biopsy, J10157	Ileal biopsy	total RNA
`GSM3975993`	Ileal biopsy, J10186	Ileal biopsy	total RNA
`GSM3975995`	Ileal biopsy, J10388	Ileal biopsy	total RNA
`GSM3975996`	Ileal biopsy, J10106	Ileal biopsy	total RNA
`GSM3975998`	Ileal biopsy, J10324	Ileal biopsy	total RNA
`GSM3975999`	Ileal biopsy, J10061	Ileal biopsy	total RNA
`GSM3976001`	Ileal biopsy, J10226	Ileal biopsy	total RNA
`GSM3976002`	Ileal biopsy, J10367	Ileal biopsy	total RNA
`GSM3976004`	Ileal biopsy, J10298	Ileal biopsy	total RNA
`GSM3976005`	Ileal biopsy, J10384	Ileal biopsy	total RNA
`GSM3976007`	Ileal biopsy, J10274	Ileal biopsy	total RNA
`GSM3976008`	Ileal biopsy, J10264	Ileal biopsy	total RNA
`GSM3976009`	Ileal biopsy, J10282	Ileal biopsy	total RNA
`GSM3976011`	Ileal biopsy, J10250	Ileal biopsy	total RNA
`GSM3976012`	Ileal biopsy, J10069	Ileal biopsy	total RNA
`GSM3976014`	Ileal biopsy, J10335	Ileal biopsy	total RNA
`GSM3976015`	Ileal biopsy, J10305	Ileal biopsy	total RNA
`GSM3976017`	Ileal biopsy, J10214	Ileal biopsy	total RNA
`GSM3976018`	Ileal biopsy, J10130	Ileal biopsy	total RNA
`GSM3976020`	Ileal biopsy, J10117	Ileal biopsy	total RNA
`GSM3976021`	Ileal biopsy, J10382	Ileal biopsy	total RNA
`GSM3976023`	Ileal biopsy, J10233	Ileal biopsy	total RNA
`GSM3976024`	Ileal biopsy, J10217	Ileal biopsy	total RNA
`GSM3976026`	Ileal biopsy, J10303	Ileal biopsy	total RNA
`GSM3976027`	Ileal biopsy, J10391	Ileal biopsy	total RNA
`GSM3976029`	Ileal biopsy, J10405	Ileal biopsy	total RNA
`GSM3976030`	Ileal biopsy, J10311	Ileal biopsy	total RNA
`GSM3976032`	Ileal biopsy, J10236	Ileal biopsy	total RNA
`GSM3976033`	Ileal biopsy, J10158	Ileal biopsy	total RNA
`GSM3976035`	Ileal biopsy, J10394	Ileal biopsy	total RNA
`GSM3976036`	Ileal biopsy, J10331	Ileal biopsy	total RNA
`GSM3976038`	Ileal biopsy, J10299	Ileal biopsy	total RNA
`GSM3976039`	Ileal biopsy, J10271	Ileal biopsy	total RNA
`GSM3976040`	Ileal biopsy, J10133	Ileal biopsy	total RNA
`GSM3976042`	Ileal biopsy, J10212	Ileal biopsy	total RNA
`GSM3976043`	Ileal biopsy, J10019	Ileal biopsy	total RNA
`GSM3976045`	Ileal biopsy, J10039	Ileal biopsy	total RNA
`GSM3976046`	Ileal biopsy, J10224	Ileal biopsy	total RNA
`GSM3976047`	Ileal biopsy, J10056	Ileal biopsy	total RNA
`GSM3976049`	Ileal biopsy, J10172	Ileal biopsy	total RNA
`GSM3976050`	Ileal biopsy, J10227	Ileal biopsy	total RNA
`GSM3976052`	Ileal biopsy, J10334	Ileal biopsy	total RNA
`GSM3976053`	Ileal biopsy, J10256	Ileal biopsy	total RNA
`GSM3976054`	Ileal biopsy, J10300	Ileal biopsy	total RNA
`GSM3976056`	Ileal biopsy, J10375	Ileal biopsy	total RNA
`GSM3976057`	Ileal biopsy, J10390	Ileal biopsy	total RNA
`GSM3976059`	Ileal biopsy, J10081	Ileal biopsy	total RNA
`GSM3976060`	Ileal biopsy, J10047	Ileal biopsy	total RNA
`GSM3976062`	Ileal biopsy, J10046	Ileal biopsy	total RNA
`GSM3976063`	Ileal biopsy, J10378	Ileal biopsy	total RNA
`GSM3976065`	Ileal biopsy, J10406	Ileal biopsy	total RNA
`GSM3976066`	Ileal biopsy, J10131	Ileal biopsy	total RNA
`GSM3976068`	Ileal biopsy, J10050	Ileal biopsy	total RNA
`GSM3976069`	Ileal biopsy, J10161	Ileal biopsy	total RNA
`GSM3976071`	Ileal biopsy, J10397	Ileal biopsy	total RNA
`GSM3976072`	Ileal biopsy, J10109	Ileal biopsy	total RNA
`GSM3976073`	Ileal biopsy, J10321	Ileal biopsy	total RNA
`GSM3976075`	Ileal biopsy, J10107	Ileal biopsy	total RNA
`GSM3976076`	Ileal biopsy, J10193	Ileal biopsy	total RNA
`GSM3976078`	Ileal biopsy, J10276	Ileal biopsy	total RNA
`GSM3976079`	Ileal biopsy, J10379	Ileal biopsy	total RNA
`GSM3976081`	Ileal biopsy, J10319	Ileal biopsy	total RNA
`GSM3976082`	Ileal biopsy, J10074	Ileal biopsy	total RNA
`GSM3976083`	Ileal biopsy, J10132	Ileal biopsy	total RNA
`GSM3976085`	Ileal biopsy, J10222	Ileal biopsy	total RNA
`GSM3976086`	Ileal biopsy, J10071	Ileal biopsy	total RNA
`GSM3976088`	Ileal biopsy, J10228	Ileal biopsy	total RNA
`GSM3976089`	Ileal biopsy, J10399	Ileal biopsy	total RNA
`GSM3976091`	Ileal biopsy, J10267	Ileal biopsy	total RNA
`GSM3976092`	Ileal biopsy, J10296	Ileal biopsy	total RNA
`GSM3976094`	Ileal biopsy, J10104	Ileal biopsy	total RNA
`GSM3976095`	Ileal biopsy, J10257	Ileal biopsy	total RNA
`GSM3976096`	Ileal biopsy, J10009	Ileal biopsy	total RNA
`GSM3976098`	Ileal biopsy, J10302	Ileal biopsy	total RNA
`GSM3976099`	Ileal biopsy, J10230	Ileal biopsy	total RNA
`GSM3976101`	Ileal biopsy, J10333	Ileal biopsy	total RNA
`GSM3976102`	Ileal biopsy, J10383	Ileal biopsy	total RNA
`GSM3976104`	Ileal biopsy, J10025	Ileal biopsy	total RNA
`GSM3976106`	Ileal biopsy, J10111	Ileal biopsy	total RNA
`GSM3976107`	Ileal biopsy, J10395	Ileal biopsy	total RNA
`GSM3976109`	Ileal biopsy, J10295	Ileal biopsy	total RNA
`GSM3976110`	Ileal biopsy, J10330	Ileal biopsy	total RNA
`GSM3976111`	Ileal biopsy, J10320	Ileal biopsy	total RNA
`GSM3976113`	Ileal biopsy, J10401	Ileal biopsy	total RNA
`GSM3976114`	Ileal biopsy, J10381	Ileal biopsy	total RNA
`GSM3976116`	Ileal biopsy, J10215	Ileal biopsy	total RNA
`GSM3976117`	Ileal biopsy, J10030	Ileal biopsy	total RNA
`GSM3976119`	Ileal biopsy, J10328	Ileal biopsy	total RNA
`GSM3976120`	Ileal biopsy, J10007	Ileal biopsy	total RNA
`GSM3976122`	Ileal biopsy, J10100	Ileal biopsy	total RNA
`GSM3976123`	Ileal biopsy, J10151	Ileal biopsy	total RNA
`GSM3976125`	Ileal biopsy, J10155	Ileal biopsy	total RNA
`GSM3976126`	Ileal biopsy, J10188	Ileal biopsy	total RNA
`GSM3976127`	Ileal biopsy, J10194	Ileal biopsy	total RNA
`GSM3976129`	Ileal biopsy, J10207	Ileal biopsy	total RNA
`GSM3976130`	Ileal biopsy, J10216	Ileal biopsy	total RNA
`GSM3976132`	Ileal biopsy, J10279	Ileal biopsy	total RNA
`GSM3976133`	Ileal biopsy, J10293	Ileal biopsy	total RNA
`GSM3976135`	Ileal biopsy, J10337	Ileal biopsy	total RNA
`GSM3976136`	Ileal biopsy, J10340	Ileal biopsy	total RNA
`GSM3976138`	Ileal biopsy, J10361	Ileal biopsy	total RNA

Strengths & limitations for reuse

Strengths

Raw reads are advertised
Processed matrices are advertised
Participant counts are documented

Limitations

Not documented: raw counts are advertised
Not documented: cell metadata are advertised

Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

Field	Value	Evidence
`assay.assay_type`	RNA-Seq	"library_strategy": "RNA-Seq" Section `samples`, offset —
`assay.library_chemistry`	TruSeq RNA Sample preparation (Illumina)	library preparation were performed using TruSeq RNA Sample preparation (Illumina) Section `extract protocol`, offset —
`assay.platform`	Illumina HiSeq 2000	Illumina HiSeq 2000 Section `samples`, offset —
`assay.reference_genome`	Gencode v23	Gencode v23 as the reference genome Section `samples`, offset —

Cohort

Field	Value	Evidence
`cohort.age_group`	paediatric from source	GEO age characteristics: 6.6; A1a; 8.0; A1a; 9.2; A1a; 9.5; A1a; 10.4; A1b; 10.7; A1b; 11.8; A1b; 12.6; A1b; 12.8; A1b; 13.6; A1b; 13.8; A1b; 14.2; A1b; 14.3; A1b; 14.8; A1b; 14.8; A1b; 14.8; A1b; 15.4; A1b; 15.8; A1b; 15.8; A1b; 15.9; A1b; 16.9; A1b; 6.2; A1a; 6.3; A1a; 6.5; A1a; 7.2; A1a; 7.3; A1a; 7.6; A1a; 7.7; A1a; 7.9 Section `GEO family SOFT`, offset —
`cohort.crohns_disease_participants`	199	Ileal gene expression profiles were analyzed for 199 treatment-naïve pediatric Crohn patients and non-IBD controls Section `series`, offset —
`cohort.disease_activity_metadata_available`	True	inflammation Section `samples`, offset —
`cohort.study_design`	cross_sectional inferred	Ileal biopsies were obtained at diagnostic colonoscopies Section `sample metadata`, offset —
`cohort.total_participants`	199	Ileal gene expression profiles were analyzed for 199 treatment-naïve pediatric Crohn patients and non-IBD controls Section `series`, offset —
`cohort.treatment_exposure_documented`	True	Ileal gene expression profiles were analyzed for 199 treatment-naïve pediatric Crohn patients and non-IBD controls Section `series_overall_design`, offset —

Data_Assets

Field	Value	Evidence
`data_assets.open_access`	True	Public on Aug 21 2019 Section `series.series_status`, offset —
`data_assets.participant_metadata`	True	"diagnosis": "CD" Section `samples`, offset —
`data_assets.processed_matrix`	True	GSE134881_RISKfpkmAll.csv.gz Section `series.series_supplementary_file`, offset —
`data_assets.raw_reads`	True	"relationtype": "SRA", "targetobject": "SRP216403" Section `external relations`, offset —

Processing

Field Value Evidence

Field	Value	Evidence
`processing.normalization_method`	transcripts per million	with transcripts per million as the output Section `sample metadata`, offset —

processing.normalization_method

transcripts per million

with transcripts per million as the output

Section sample metadata, offset —

Specimens

Field	Value	Evidence
`specimens.anatomical_sites`	['ileum']	Ileal biopsy Section `samples`, offset —
`specimens.inflamed_status_available`	True	"inflammation": "Histologically involved" Section `samples`, offset —
`specimens.number_of_samples`	199	"sample_count": 199 Section `sample_count`, offset —
`specimens.specimen_type`	biopsy	Ileal biopsy, J10352 Section `samples`, offset —