کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5649509 | 1407126 | 2017 | 29 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A Functional Genomic Meta-Analysis of Clinical Trials in Systemic Sclerosis: Toward Precision Medicine and Combination Therapy
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کلمات کلیدی
SSCMMFGSEATGF-βsystemic sclerosis - اسکلروز سیستمیکtransforming growth factor-β - تبدیل فاکتور رشد βGene Set Enrichment Analysis - تجزیه و تحلیل غنی سازی مجموعه ژنیDEG - شماGiant - غولSupport vector machine - ماشین بردار پشتیبانیSVM - ماشین بردار پشتیبانیmycophenolate mofetil - مایکوفنولات موفتیلDifferentially expressed gene - ژن بیان شده متفاوت است
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
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چکیده انگلیسی
Systemic sclerosis is an orphan, systemic autoimmune disease with no FDA-approved treatments. Its heterogeneity and rarity often result in underpowered clinical trials making the analysis and interpretation of associated molecular data challenging. We performed a meta-analysis of gene expression data from skin biopsies of patients with systemic sclerosis treated with five therapies: mycophenolate mofetil, rituximab, abatacept, nilotinib, and fresolimumab. A common clinical improvement criterion of â20% or â5 modified Rodnan skin score was applied to each study. We applied a machine learning approach that captured features beyond differential expression and was better at identifying targets of therapies than the differential expression alone. Regardless of treatment mechanism, abrogation of inflammatory pathways accompanied clinical improvement in multiple studies suggesting that high expression of immune-related genes indicates active and targetable disease. Our framework allowed us to compare different trials and ask if patients who failed one therapy would likely improve on a different therapy, based on changes in gene expression. Genes with high expression at baseline in fresolimumab nonimprovers were downregulated in mycophenolate mofetil improvers, suggesting that immunomodulatory or combination therapy may have benefitted these patients. This approach can be broadly applied to increase tissue specificity and sensitivity of differential expression results.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 137, Issue 5, May 2017, Pages 1033-1041
Journal: Journal of Investigative Dermatology - Volume 137, Issue 5, May 2017, Pages 1033-1041
نویسندگان
Jaclyn N. Taroni, Viktor Martyanov, J. Matthew Mahoney, Michael L. Whitfield,