scholarly journals Identification of Candidate Genes Related to Inflammatory Bowel Disease Using Minimum Redundancy Maximum Relevance, Incremental Feature Selection, and the Shortest-Path Approach

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Fei Yuan ◽  
Yu-Hang Zhang ◽  
Xiang-Yin Kong ◽  
Yu-Dong Cai

Identification of disease genes is a hot topic in biomedicine and genomics. However, it is a challenging problem because of the complexity of diseases. Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to host intestinal microflora. It has been proven to be associated with the development of intestinal malignancies. Although the specific pathological characteristics and genetic background of IBD have been partially revealed, it is still an overdetermined disease and the blueprint of all genetic variants still needs to be improved. In this study, a novel computational method was built to identify genes related to IBD. Samples from two subtypes of IBD (ulcerative colitis and Crohn’s disease) and normal samples were employed. By analyzing the gene expression profiles of these samples using minimum redundancy maximum relevance and incremental feature selection, 21 genes were obtained that could effectively distinguish samples from the two subtypes of IBD and the normal samples. Then, the shortest-path approach was used to search for an additional 20 genes in a large network constructed using protein-protein interactions based on the above-mentioned 21 genes. Analyses of the 41 genes obtained indicate that they are closely associated with this disease.

2020 ◽  
Vol 21 (9) ◽  
pp. 3364 ◽  
Author(s):  
Sara Salvador-Martín ◽  
Irene Raposo-Gutiérrez ◽  
Víctor Manuel Navas-López ◽  
Carmen Gallego-Fernández ◽  
Ana Moreno-Álvarez ◽  
...  

Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.


2020 ◽  
Vol 158 (6) ◽  
pp. S-792-S-793
Author(s):  
Jan Nowak ◽  
Alex Adams ◽  
Rahul Kalla ◽  
Daniel Bergemalm ◽  
Simen Vatn ◽  
...  

2020 ◽  
Vol 26 (7) ◽  
pp. 985-993 ◽  
Author(s):  
Petr Jabandziev ◽  
Julia Bohosova ◽  
Tereza Pinkasova ◽  
Lumir Kunovsky ◽  
Ondrej Slaby ◽  
...  

Abstract Prevalence of inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gut, has been on the rise in recent years—not only in the adult population but also especially in pediatric patients. Despite the absence of curative treatments, current therapeutic options are able to achieve long-term remission in a significant proportion of cases. To this end, however, there is a need for biomarkers enabling accurate diagnosis, prognosis, and prediction of response to therapies to facilitate a more individualized approach to pediatric IBD patients. In recent years, evidence has continued to evolve concerning noncoding RNAs (ncRNAs) and their roles as integral factors in key immune-related cellular pathways. Specific deregulation patterns of ncRNAs have been linked to pathogenesis of various diseases, including pediatric IBD. In this article, we provide an overview of current knowledge on ncRNAs, their altered expression profiles in pediatric IBD patients, and how these are emerging as potentially valuable clinical biomarkers as we enter an era of personalized medicine.


2013 ◽  
Vol 173 (2) ◽  
pp. 250-258 ◽  
Author(s):  
M. Iborra ◽  
F. Bernuzzi ◽  
C. Correale ◽  
S. Vetrano ◽  
G. Fiorino ◽  
...  

2018 ◽  
Vol 24 (10) ◽  
pp. 2285-2290 ◽  
Author(s):  
Raguraj Chandradevan ◽  
Tatyana Hofmekler ◽  
Kajari Mondal ◽  
Nusrat Harun ◽  
Suresh Venkateswaran ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 77
Author(s):  
Sara Salvador-Martín ◽  
Bartosz Kaczmarczyk ◽  
Rebeca Álvarez ◽  
Víctor Manuel Navas-López ◽  
Carmen Gallego-Fernández ◽  
...  

Background: Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: An observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged < 18 years who started treatment with infliximab or adalimumab (29 responders and nine non-responders). Whole gene expression profiles from total RNA isolated from whole blood samples of six responders and six non-responders taken before administration of the biologic and after two weeks of therapy were analyzed using next-generation RNA sequencing. The expression of six selected genes was measured for purposes of validation in all of the 38 patients recruited using qPCR. Results: Genes were differentially expressed in non-responders and responders (32 before initiation of treatment and 44 after two weeks, Log2FC (Fold change) >0.6 or <−0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, p value < 0.05). Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.


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