 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Apr 01, 2015 |
| Title |
Fibrotic and Immune Pathway Signatures in Systemic Sclerosis Suggest a Progressive, Multi-step Model of Disease Pathogenesis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Pathway expression analysis in systemic sclerosis revealed key mediators driving pathology within each of the intrinsic gene expression subsets.
Genome-wide expression profiling in systemic sclerosis (SSc) has identified four 'intrinsic' subsets of disease (fibroproliferative, inflammatory, limited, and normal-like), each of which appear to be driven by distinct signaling pathways. Here we examine experimentally derived gene expression signatures for thirteen agonists to better understand the molecular mechanisms underlying each intrinsic subsets. Pathway-specific gene signatures were compared against skin biopsy microarray data consisting of 329 microarray hybridizations from 287 unique biopsies representing 111 patients. Hierarchical clustering recapitulated the four SSc 'intrinsic' gene expression subsets, along with an intermediate subset exhibiting both inflammatory and fibroproliferative gene expression signatures. The fibroproliferative subset is most strongly associated with the PDGF gene signature, while the inflammatory subset demonstrated strong activation of NF-kappaB, characterized by early induction of TH2 signals, which transitions to a more TH17-like immune response over time. The limited subset was associated with IFNalpha signaling, combined with strong downregulation of PDGF signaling. The inflammatory-proliferative subset shows downregulation of NF-kappaB-associated pathways in conjunction with increased PDGF signaling, suggestive of a transitional state linking the inflammatory and fibroproliferative subsets. IL-13 signaling was strongly associated with early disease, while TGFbeta signaling was associated with more severe disease. Together these data suggest a multi-step, progressive model of disease pathogenesis driven by distinct pathways. Targeting these pathways based upon a patient's underlying disease subset should improve therapeutic outcomes.
|
| |
|
| Overall design |
In vitro treatment of human dermal fibroblasts was performed to identify pathway-specific gene signatures. These gene signatures were then compared against systemic sclerosis skin biopsy microarrays to determine the overall contribution of each pathway to disease.
This study includes re-analysis of 247 skin biopsy samples from GSE9285, GSE32413, and GSE45485. Links to these Samples are provided below. The re-processed normalized data for these Samples are included in the supplementary file 'GSE56308_247_Skin_Biopsy_Reanalysis_Samples.txt'.
|
| |
|
| Contributor(s) |
Johnson ME, Mahoney JM, Taroni J, Sargent JL, Marmarelis E, Wu MR, Varga J, Hinchcliff M, Whitfield ML |
| Citation(s) |
25607805 |
| |
| Submission date |
Mar 27, 2014 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Tammara Wood |
| E-mail(s) |
[email protected]
|
| Organization name |
Dartmouth Medical School
|
| Department |
Biomedical Data Science
|
| Lab |
Whitfield Lab
|
| Street address |
WTRB 674
|
| City |
Lebanon |
| State/province |
NH |
| ZIP/Postal code |
03756 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
|
| Samples (94)
|
|
| Relations |
| Reanalysis of |
GSM1104220 |
| Reanalysis of |
GSM1104221 |
| Reanalysis of |
GSM1104222 |
| Reanalysis of |
GSM1104223 |
| Reanalysis of |
GSM1104224 |
| Reanalysis of |
GSM1104225 |
| Reanalysis of |
GSM1104226 |
| Reanalysis of |
GSM1104227 |
| Reanalysis of |
GSM1104228 |
| Reanalysis of |
GSM1104229 |
| Reanalysis of |
GSM1104230 |
| Reanalysis of |
GSM1104231 |
| Reanalysis of |
GSM1104232 |
| Reanalysis of |
GSM1104233 |
| Reanalysis of |
GSM1104234 |
| Reanalysis of |
GSM1104235 |
| Reanalysis of |
GSM1104236 |
| Reanalysis of |
GSM1104237 |
| Reanalysis of |
GSM1104238 |
| Reanalysis of |
GSM1104239 |
| Reanalysis of |
GSM1104240 |
| Reanalysis of |
GSM1104241 |
| Reanalysis of |
GSM1104242 |
| Reanalysis of |
GSM1104243 |
| Reanalysis of |
GSM1104244 |
| Reanalysis of |
GSM1104245 |
| Reanalysis of |
GSM1104246 |
| Reanalysis of |
GSM1104247 |
| Reanalysis of |
GSM1104248 |
| Reanalysis of |
GSM1104249 |
| Reanalysis of |
GSM1104250 |
| Reanalysis of |
GSM1104251 |
| Reanalysis of |
GSM1104252 |
| Reanalysis of |
GSM1104253 |
| Reanalysis of |
GSM1104254 |
| Reanalysis of |
GSM1104255 |
| Reanalysis of |
GSM1104256 |
| Reanalysis of |
GSM1104257 |
| Reanalysis of |
GSM1104258 |
| Reanalysis of |
GSM1104259 |
| Reanalysis of |
GSM1104260 |
| Reanalysis of |
GSM1104261 |
| Reanalysis of |
GSM1104262 |
| Reanalysis of |
GSM1104263 |
| Reanalysis of |
GSM1104264 |
| Reanalysis of |
GSM1104265 |
| Reanalysis of |
GSM1104266 |
| Reanalysis of |
GSM1104267 |
| Reanalysis of |
GSM1104268 |
| Reanalysis of |
GSM1104269 |
| Reanalysis of |
GSM1104270 |
| Reanalysis of |
GSM1104271 |
| Reanalysis of |
GSM1104272 |
| Reanalysis of |
GSM1104273 |
| Reanalysis of |
GSM1104274 |
| Reanalysis of |
GSM1104275 |
| Reanalysis of |
GSM1104276 |
| Reanalysis of |
GSM1104277 |
| Reanalysis of |
GSM1104278 |
| Reanalysis of |
GSM1104279 |
| Reanalysis of |
GSM1104280 |
| Reanalysis of |
GSM1104281 |
| Reanalysis of |
GSM1104282 |
| Reanalysis of |
GSM1104283 |
| Reanalysis of |
GSM1104284 |
| Reanalysis of |
GSM1104285 |
| Reanalysis of |
GSM1104286 |
| Reanalysis of |
GSM1104287 |
| Reanalysis of |
GSM1104288 |
| Reanalysis of |
GSM1104289 |
| Reanalysis of |
GSM1104290 |
| Reanalysis of |
GSM1104291 |
| Reanalysis of |
GSM1104292 |
| Reanalysis of |
GSM1104293 |
| Reanalysis of |
GSM1104294 |
| Reanalysis of |
GSM1104295 |
| Reanalysis of |
GSM1104296 |
| Reanalysis of |
GSM1104297 |
| Reanalysis of |
GSM1104298 |
| Reanalysis of |
GSM1104299 |
| Reanalysis of |
GSM1104300 |
| Reanalysis of |
GSM1104301 |
| Reanalysis of |
GSM1104302 |
| Reanalysis of |
GSM236379 |
| Reanalysis of |
GSM236380 |
| Reanalysis of |
GSM236381 |
| Reanalysis of |
GSM236382 |
| Reanalysis of |
GSM236383 |
| Reanalysis of |
GSM236384 |
| Reanalysis of |
GSM236385 |
| Reanalysis of |
GSM236386 |
| Reanalysis of |
GSM236387 |
| Reanalysis of |
GSM236388 |
| Reanalysis of |
GSM236389 |
| Reanalysis of |
GSM236390 |
| Reanalysis of |
GSM236391 |
| Reanalysis of |
GSM236392 |
| Reanalysis of |
GSM236393 |
| Reanalysis of |
GSM236394 |
| Reanalysis of |
GSM236395 |
| Reanalysis of |
GSM236396 |
| Reanalysis of |
GSM236397 |
| Reanalysis of |
GSM236398 |
| Reanalysis of |
GSM236399 |
| Reanalysis of |
GSM236400 |
| Reanalysis of |
GSM236401 |
| Reanalysis of |
GSM236402 |
| Reanalysis of |
GSM236403 |
| Reanalysis of |
GSM236404 |
| Reanalysis of |
GSM236405 |
| Reanalysis of |
GSM236406 |
| Reanalysis of |
GSM236407 |
| Reanalysis of |
GSM236408 |
| Reanalysis of |
GSM236409 |
| Reanalysis of |
GSM236410 |
| Reanalysis of |
GSM236411 |
| Reanalysis of |
GSM236412 |
| Reanalysis of |
GSM236413 |
| Reanalysis of |
GSM236414 |
| Reanalysis of |
GSM236415 |
| Reanalysis of |
GSM236416 |
| Reanalysis of |
GSM236417 |
| Reanalysis of |
GSM236418 |
| Reanalysis of |
GSM236419 |
| Reanalysis of |
GSM236420 |
| Reanalysis of |
GSM236421 |
| Reanalysis of |
GSM236422 |
| Reanalysis of |
GSM236423 |
| Reanalysis of |
GSM236424 |
| Reanalysis of |
GSM236425 |
| Reanalysis of |
GSM236426 |
| Reanalysis of |
GSM236427 |
| Reanalysis of |
GSM236428 |
| Reanalysis of |
GSM236429 |
| Reanalysis of |
GSM236430 |
| Reanalysis of |
GSM236431 |
| Reanalysis of |
GSM236432 |
| Reanalysis of |
GSM236433 |
| Reanalysis of |
GSM236434 |
| Reanalysis of |
GSM236435 |
| Reanalysis of |
GSM236436 |
| Reanalysis of |
GSM236437 |
| Reanalysis of |
GSM236438 |
| Reanalysis of |
GSM236439 |
| Reanalysis of |
GSM236440 |
| Reanalysis of |
GSM236441 |
| Reanalysis of |
GSM236442 |
| Reanalysis of |
GSM236443 |
| Reanalysis of |
GSM236444 |
| Reanalysis of |
GSM236445 |
| Reanalysis of |
GSM236446 |
| Reanalysis of |
GSM236447 |
| Reanalysis of |
GSM236448 |
| Reanalysis of |
GSM236449 |
| Reanalysis of |
GSM236450 |
| Reanalysis of |
GSM236451 |
| Reanalysis of |
GSM236452 |
| Reanalysis of |
GSM236453 |
| Reanalysis of |
GSM801988 |
| Reanalysis of |
GSM801989 |
| Reanalysis of |
GSM801990 |
| Reanalysis of |
GSM801991 |
| Reanalysis of |
GSM801992 |
| Reanalysis of |
GSM801993 |
| Reanalysis of |
GSM801994 |
| Reanalysis of |
GSM801995 |
| Reanalysis of |
GSM801996 |
| Reanalysis of |
GSM801997 |
| Reanalysis of |
GSM801998 |
| Reanalysis of |
GSM801999 |
| Reanalysis of |
GSM802000 |
| Reanalysis of |
GSM802001 |
| Reanalysis of |
GSM802002 |
| Reanalysis of |
GSM802003 |
| Reanalysis of |
GSM802004 |
| Reanalysis of |
GSM802005 |
| Reanalysis of |
GSM802006 |
| Reanalysis of |
GSM802007 |
| Reanalysis of |
GSM802008 |
| Reanalysis of |
GSM802009 |
| Reanalysis of |
GSM802010 |
| Reanalysis of |
GSM802011 |
| Reanalysis of |
GSM802012 |
| Reanalysis of |
GSM802013 |
| Reanalysis of |
GSM802014 |
| Reanalysis of |
GSM802015 |
| Reanalysis of |
GSM802016 |
| Reanalysis of |
GSM802017 |
| Reanalysis of |
GSM802018 |
| Reanalysis of |
GSM802019 |
| Reanalysis of |
GSM802020 |
| Reanalysis of |
GSM802021 |
| Reanalysis of |
GSM802022 |
| Reanalysis of |
GSM802023 |
| Reanalysis of |
GSM802024 |
| Reanalysis of |
GSM802025 |
| Reanalysis of |
GSM802026 |
| Reanalysis of |
GSM802027 |
| Reanalysis of |
GSM802028 |
| Reanalysis of |
GSM802029 |
| Reanalysis of |
GSM802030 |
| Reanalysis of |
GSM802031 |
| Reanalysis of |
GSM802032 |
| Reanalysis of |
GSM802033 |
| Reanalysis of |
GSM802034 |
| Reanalysis of |
GSM802035 |
| Reanalysis of |
GSM802036 |
| Reanalysis of |
GSM802037 |
| Reanalysis of |
GSM802038 |
| Reanalysis of |
GSM802039 |
| Reanalysis of |
GSM802040 |
| Reanalysis of |
GSM802041 |
| Reanalysis of |
GSM802042 |
| Reanalysis of |
GSM802043 |
| Reanalysis of |
GSM802044 |
| Reanalysis of |
GSM802045 |
| Reanalysis of |
GSM802046 |
| Reanalysis of |
GSM802047 |
| Reanalysis of |
GSM802048 |
| Reanalysis of |
GSM802049 |
| Reanalysis of |
GSM802050 |
| Reanalysis of |
GSM802051 |
| Reanalysis of |
GSM802052 |
| Reanalysis of |
GSM802053 |
| Reanalysis of |
GSM802054 |
| Reanalysis of |
GSM802055 |
| Reanalysis of |
GSM802056 |
| Reanalysis of |
GSM802057 |
| Reanalysis of |
GSM802058 |
| Reanalysis of |
GSM802059 |
| Reanalysis of |
GSM802060 |
| Reanalysis of |
GSM802061 |
| Reanalysis of |
GSM802062 |
| Reanalysis of |
GSM802063 |
| Reanalysis of |
GSM802064 |
| Reanalysis of |
GSM802065 |
| Reanalysis of |
GSM802066 |
| Reanalysis of |
GSM802067 |
| Reanalysis of |
GSM802068 |
| Reanalysis of |
GSM802069 |
| Reanalysis of |
GSM802070 |
| Reanalysis of |
GSM802071 |
| Reanalysis of |
GSM802072 |
| Reanalysis of |
GSM802073 |
| Reanalysis of |
GSM802074 |
| Reanalysis of |
GSM802075 |
| Reanalysis of |
GSM802076 |
| BioProject |
PRJNA244937 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56308_247_Skin_Biopsy_Reanalysis_Samples.txt.gz |
11.4 Mb |
(ftp)(http) |
TXT |
| GSE56308_RAW.tar |
1.5 Gb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...