@article{a3acc1070a03460692fc36a6f23b2778,
title = "Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response",
abstract = " Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α 4 β 7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches.",
author = "Yael Haberman and Rebekah Karns and Dexheimer, {Phillip J.} and Melanie Schirmer and Judith Somekh and Ingrid Jurickova and Tzipi Braun and Elizabeth Novak and Laura Bauman and Collins, {Margaret H.} and Angela Mo and Rosen, {Michael J.} and Erin Bonkowski and Nathan Gotman and Alison Marquis and Mason Nistel and Rufo, {Paul A.} and Baker, {Susan S.} and Sauer, {Cary G.} and James Markowitz and Pfefferkorn, {Marian D.} and Rosh, {Joel R.} and Boyle, {Brendan M.} and Mack, {David R.} and Baldassano, {Robert N.} and Sapana Shah and Leleiko, {Neal S.} and Heyman, {Melvin B.} and Grifiths, {Anne M.} and Patel, {Ashish S.} and Noe, {Joshua D.} and Aronow, {Bruce J.} and Subra Kugathasan and Walters, {Thomas D.} and Greg Gibson and Thomas, {Sonia Davis} and Kevin Mollen and Shai Shen-Orr and Curtis Huttenhower and Xavier, {Ramnik J.} and Hyams, {Jeffrey S.} and Denson, {Lee A.}",
note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-018-07841-3",
language = "אנגלית",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}