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Article ; Online: Combining machine learning and structure-based approaches to develop oncogene PIM kinase inhibitors

Haifa Almukadi / Gada Ali Jadkarim / Arif Mohammed / Majid Almansouri / Nasreen Sultana / Noor Ahmad Shaik / Babajan Banaganapalli

Frontiers in Chemistry, Vol

2023 Volume 11

Abstract: Introduction: PIM kinases are targets for therapeutic intervention since they are associated with a number of malignancies by boosting cell survival and proliferation. Over the past years, the rate of new PIM inhibitors discovery has increased ... ...

Abstract	Introduction: PIM kinases are targets for therapeutic intervention since they are associated with a number of malignancies by boosting cell survival and proliferation. Over the past years, the rate of new PIM inhibitors discovery has increased significantly, however, new generation of potent molecules with the right pharmacologic profiles were in demand that can probably lead to the development of Pim kinase inhibitors that are effective against human cancer.Method: In the current study, a machine learning and structure based approaches were used to generate novel and effective chemical therapeutics for PIM-1 kinase. Four different machine learning methods, namely, support vector machine, random forest, k-nearest neighbour and XGBoost have been used for the development of models. Total, 54 Descriptors have been selected using the Boruta method.Results: SVM, Random Forest and XGBoost shows better performance as compared to k-NN. An ensemble approach was implemented and, finally, four potential molecules (CHEMBL303779, CHEMBL690270, MHC07198, and CHEMBL748285) were found to be effective for the modulation of PIM-1 activity. Molecular docking and molecular dynamic simulation corroborated the potentiality of the selected molecules. The molecular dynamics (MD) simulation study indicated the stability between protein and ligands.Discussion: Our findings suggest that the selected models are robust and can be potentially useful for facilitating the discovery against PIM kinase.
Keywords	PIM kinase ; classification models ; virtual screening ; molecular docking ; cancer drug treatment ; Chemistry ; QD1-999
Subject code	006
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification of novel mycobacterium tuberculosis leucyl-tRNA synthetase inhibitor using a knowledge-based computational screening approach

Faten Ahmad Alsulaimany / Haifa Almukadi / Nidal M. Omer Zabermawi / Thamer Abdulhamid Aljuhani / Omran M. Rashidi / Walaa F. Albaqami / Anwar A. Alghamdi / Aftab Ahmad / Noor Ahmad Shaik / Babajan Banaganapalli

Journal of King Saud University: Science, Vol 34, Iss 4, Pp 102032- (2022)

2022

Abstract: Objectives: Tuberculosis is a chronic lung disease caused by Mycobacterium tuberculosis (MTB), whose thick cell envelope and drug metabolizing enzymes offering it multidrug resistance. Therefore, there is a need to identify new molecular targets, ... ...

Abstract	Objectives: Tuberculosis is a chronic lung disease caused by Mycobacterium tuberculosis (MTB), whose thick cell envelope and drug metabolizing enzymes offering it multidrug resistance. Therefore, there is a need to identify new molecular targets, biologically active as well as clinically safe anti-MTB compounds from natural resources. Methods: In this study, we performed high throughput computational screening of FDA listed natural bioactive compounds for identifying novel anti-MTB leucyl-tRNA (LeuRS) synthetase inhibitors. Results: Initial virtual molecular docking of 136 bioactive compounds has identified Docetaxel, Reserpine and Irinotecan as promising lead molecules owing to their structural plasticity and binding affinity with the active site of MTB-LeuRS. Further, deep molecular docking and molecular dynamics (MD) simulation analysis (at 100 ns) of the above three test compounds along with Oxaborole compound (GSK656) has demonstrated the superior binding affinity and stability of Irinotecan in forming molecular complexes with LeuRS protein. Interestingly, it also showed comparable binding residues and affinity parameters (like flexibility, structural divergence) as the GSK656 inhibitor in binding the tRNASyn domain 2 of LeuRS. A good correlation of pharmacokinetic properties (ADME-Tox) like bioavailability, absorption, solubility, and low toxicity between Irinotecan and GSK656 was evident. Competitive binding of Irinotecan to tRNASyn domain 2 of LeuRS is likely to make it unavailable to bind Leucine amino acid, which may negatively impact the protein biosynthesis and eventually inhibit the bacterial growth and attenuate the pathogen’s virulence. Conclusions: Our findings pave the way for further experimental confirmation of Irinotecan in the quest for a novel anti-LeuRS specific inhibitor to combat drug resistant MTB infection.
Keywords	Mycobacterium tuberculosis ; Deep docking ; Bioactive compounds ; MD simulation ; tRNA ; Drug resistance ; Science (General) ; Q1-390
Subject code	540
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genetic association study of NOD2 and IL23R amino acid substitution polymorphisms in Saudi Inflammatory Bowel Disease patients

Raneem Saadi Alharbi / Noor Ahmad Shaik / Hadiah Almahdi / Hanan Abdelhalim ElSokary / Bassam Adnan Jamalalail / Mahmoud H. Mosli / Hadeel A. Alsufyani / Jumana Yousuf Al-Aama / Ramu Elango / Omar Ibrahim Saadah / Babajan Banaganapalli

Journal of King Saud University: Science, Vol 34, Iss 1, Pp 101726- (2022)

2022

Abstract: Background: Inflammatory Bowel Disease (IBD) is a complex autoimmune disease whose genetic basis is not well explored in the highly consanguineous Saudi population. Therefore, this study aims to evaluate the relevance of NOD2 and IL23R genes ... ...

Abstract	Background: Inflammatory Bowel Disease (IBD) is a complex autoimmune disease whose genetic basis is not well explored in the highly consanguineous Saudi population. Therefore, this study aims to evaluate the relevance of NOD2 and IL23R genes polymorphisms, selected from Caucasian Genome-wide association study (GWAS) findings, as risk markers for IBD pathology in Saudi patients. Materials and Methods: The genetic status of NOD2 and IL23R polymorphisms of 97 IBD patients and 100 healthy individuals was determined through real-time PCR based TaqMan Allelic Discrimination Assay. Genotype calls of TaqMan assay were further validated by the direct DNA sequencing method. The pathogenicity of the variants was further explored by computational predictions and by 3D structural modelling methods. Results: Our study found no evidence for a significant association of Caucasian IBD risk alleles, i.e., NOD2 (P268S and R702W) and IL23R (G149R and R381Q) with IBD pathology in Saudi Arabian patients under dominant, recessive or co-dominant genetic models. Moreover, SNP-SNP interaction analysis with multidimensionality reduction assays have also confirmed the above findings. Our computational predictions of the variants suggest the variable deleterious nature and minor structural drifts on the tertiary protein structures. Conclusion: This study expands the genetic heterogeneity of IBD and concludes that Caucasian genetic risk markers have limited or of no use in estimating the risk of IBD development in Saudi patients. Future genetic association studies in Saudi Arabia need to employ genetic markers whose minor allele frequencies exceed 10% in Arab population to have robust outcomes.
Keywords	NOD2 ; IL23R ; Inflammatory Bowel Disease ; Crohn’s disease ; Polymorphism ; Science (General) ; Q1-390
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Transcriptome-Based Molecular Networks Uncovered Interplay Between Druggable Genes of CD8+ T Cells and Changes in Immune Cell Landscape in Patients With Pulmonary Tuberculosis

Faten Ahmad Alsulaimany / Nidal M. Omer Zabermawi / Haifa Almukadi / Snijesh V. Parambath / Preetha Jayasheela Shetty / Venkatesh Vaidyanathan / Ramu Elango / Babajan Babanaganapalli / Noor Ahmad Shaik

Frontiers in Medicine, Vol

2022 Volume 8

Abstract: BackgroundTuberculosis (TB) is a major infectious disease, where incomplete information about host genetics and immune responses is hindering the development of transformative therapies. This study characterized the immune cell landscape and blood ... ...

Abstract	BackgroundTuberculosis (TB) is a major infectious disease, where incomplete information about host genetics and immune responses is hindering the development of transformative therapies. This study characterized the immune cell landscape and blood transcriptomic profile of patients with pulmonary TB (PTB) to identify the potential therapeutic biomarkers.MethodsThe blood transcriptome profile of patients with PTB and controls were used for fractionating immune cell populations with the CIBERSORT algorithm and then to identify differentially expressed genes (DEGs) with R/Bioconductor packages. Later, systems biology investigations (such as semantic similarity, gene correlation, and graph theory parameters) were implemented to prioritize druggable genes contributing to the immune cell alterations in patients with TB. Finally, real time-PCR (RT-PCR) was used to confirm gene expression levels.ResultsPatients with PTB had higher levels of four immune subpopulations like CD8+ T cells (P = 1.9 × 10−8), natural killer (NK) cells resting (P = 6.3 × 10−5), monocytes (P = 6.4 × 10−6), and neutrophils (P = 1.6 × 10−7). The functional enrichment of 624 DEGs identified in the blood transcriptome of patients with PTB revealed major dysregulation of T cell-related ontologies and pathways (q ≤ 0.05). Of the 96 DEGs shared between transcriptome and immune cell types, 39 overlapped with TB meta-profiling genetic signatures, and their semantic similarity analysis with the remaining 57 genes, yielded 45 new candidate TB markers. This study identified 9 CD8+ T cell-associated genes (ITK, CD2, CD6, CD247, ZAP70, CD3D, SH2D1A, CD3E, and IL7R) as potential therapeutic targets of PTB by combining computational druggability and co-expression (r2 ≥ \|0.7\|) approaches.ConclusionThe changes in immune cell proportion and the downregulation of T cell-related genes may provide new insights in developing therapeutic compounds against chronic TB.
Keywords	Mycobacterium tuberculosis ; gene express profile ; drug target ; CD8+T cells ; immune pathways ; Medicine (General) ; R5-920
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identifying significant genes and functionally enriched pathways in familial hypercholesterolemia using integrated gene co-expression network analysis

Zuhier Awan / Nuha Alrayes / Zeenath Khan / Majid Almansouri / Abdulhadi Ibrahim Hussain Bima / Haifa Almukadi / Hussam Ibrahim Kutbi / Preetha Jayasheela Shetty / Noor Ahmad Shaik / Babajan Banaganapalli

Saudi Journal of Biological Sciences, Vol 29, Iss 5, Pp 3287-

2022 Volume 3299

Abstract: Familial hypercholesterolemia (FH) is a monogenic lipid disorder which promotes atherosclerosis and cardiovascular diseases. Owing to the lack of sufficient published information, this study aims to identify the potential genetic biomarkers for FH by ... ...

Abstract	Familial hypercholesterolemia (FH) is a monogenic lipid disorder which promotes atherosclerosis and cardiovascular diseases. Owing to the lack of sufficient published information, this study aims to identify the potential genetic biomarkers for FH by studying the global gene expression profile of blood cells. The microarray expression data of FH patients and controls was analyzed by different computational biology methods like differential expression analysis, protein network mapping, hub gene identification, functional enrichment of biological pathways, and immune cell restriction analysis. Our results showed the dysregulated expression of 115 genes connected to lipid homeostasis, immune responses, cell adhesion molecules, canonical Wnt signaling, mucin type O-glycan biosynthesis pathways in FH patients. The findings from expanded protein interaction network construction with known FH genes and subsequent Gene Ontology (GO) annotations have also supported the above findings, in addition to identifying the involvement of dysregulated thyroid hormone and ErbB signaling pathways in FH patients. The genes like CSNK1A1, JAK3, PLCG2, RALA, and ZEB2 were found to be enriched under all GO annotation categories. The subsequent phenotype ontology results have revealed JAK3I, PLCG2, and ZEB2 as key hub genes contributing to the inflammation underlying cardiovascular and immune response related phenotypes. Immune cell restriction findings show that above three genes are highly expressed by T-follicular helper CD4+ T cells, naïve B cells, and monocytes, respectively. These findings not only provide a theoretical basis to understand the role of immune dysregulations underlying the atherosclerosis among FH patients but may also pave the way to develop genomic medicine for cardiovascular diseases.
Keywords	Familial hypercholesterolemia ; Gene expression ; DEGs ; PPI ; Microarray ; Network ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A novel polyherbal formulation containing thymoquinone attenuates carbon tetrachloride-induced hepatorenal injury in a rat model

Aftab Ahmad / Mohammed F Abuzinadah / Huda M Alkreathy / Hussam I Kutbi / Noor Ahmad Shaik / Varish Ahmad / Shakir Saleem / Asif Husain

Asian Pacific Journal of Tropical Biomedicine, Vol 10, Iss 4, Pp 147-

2020 Volume 155

Abstract: Objective: To evaluate a novel polyherbal formulation (BSVT) containing the standardized extracts from the leaves of Boerhavia diffusa, Solidago virgaurea, Vitex negundo, and thymoquinone in CCl4 induced hepatorenal toxicity in rats. Methods: A total of ... ...

Abstract	Objective: To evaluate a novel polyherbal formulation (BSVT) containing the standardized extracts from the leaves of Boerhavia diffusa, Solidago virgaurea, Vitex negundo, and thymoquinone in CCl4 induced hepatorenal toxicity in rats. Methods: A total of 36 rats were divided into six groups including normal control, CCl4 (2 mL/kg, i.p.), CCl4 (2 mL/kg, i.p.) + Cystone® (750 mg/kgp.o.), CCl4 (2 mL/kg, i.p.) + BSVT (25 mg/ kg, p.o.), CCl4 (2 mL/kg, i.p.) + BSVT (50 mg/kg, p.o.), and CCl4 (2 mL/kg, i.p.) + BSVT (100 mg/kg,p.o.). All treatments were given for four weeks. Serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, cholesterol, total protein, serum urea, blood urea nitrogen and creatinine were assessed. Superoxide dismutase, malondialdehyde, and glutathione peroxidase were evaluated in tissue homogenate. The histopathological study of liver and kidney tissues was also done. Results: Aspartate transaminase, alanine transaminase, alkaline phosphatase, cholesterol, serum urea, blood urea nitrogen and creatinine were significantly elevated (P<0.001) while total protein was considerably reduced in the CCl4 group as compared to the normal con trol (P<0.001), which indicated hepatorenal toxicity. In addition, superoxide dismutase and glutathione peroxidase activities were significantly decreased (P<0.001) while malondialdehyde levels were increased markedly (P<0.001). Treatment with BSVT formulation recovered these parameters towards a normal level in a dose-dependent manner. Conclusions: BSVT formulation ameliorates the hepatorenal toxicity in a dose-dependent manner. Furthermore, clinical studies are required to confirm its efficacy.
Keywords	boerhavia diffusa ; solidago virgaurea ; vitex negundo ; thymoquinone ; cystone® ; carbon tetrachloride ; hepatorenal ; Arctic medicine. Tropical medicine ; RC955-962 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular designing, virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR

Noor Ahmad Shaik / Huda M. Al-Kreathy / Ghada M. Ajabnoor / Prashant Kumar Verma / Babajan Banaganapalli

Saudi Journal of Biological Sciences, Vol 26, Iss 3, Pp 439-

2019 Volume 448

Abstract: The somatic mutations in ATP binding cleft of the tyrosine kinase binding domain of EGFR are known to occur in 15–40% of non-small cell lung cancer (NSCLC) patients. Although first and second generation anti-EGFR inhibitors are widely used to treat these ...

Abstract	The somatic mutations in ATP binding cleft of the tyrosine kinase binding domain of EGFR are known to occur in 15–40% of non-small cell lung cancer (NSCLC) patients. Although first and second generation anti-EGFR inhibitors are widely used to treat these patients, their therapeutic efficacy is modest and often results in adverse effects or drug resistance. Therefore, there is a need to develop novel as well as safe anti-EGFR drugs. The rapid emergence of computational drug designing provided a great opportunity to both discover and predict the efficacy of novel EGFR inhibitors from plant sources. In the present study, we designed several chemical analogues of edible curcumin (CUCM) compound and assessed their drug likeliness, ADME and toxicity properties using a diverse range of advanced computational methods. We also have examined the structural plasticity and binding characteristics of EGFR wild-type and mutant forms (S769L and K846R) against ligand molecules like Gefitinib, native CUCM, and different CUCM analogues. Through multidimensional experimental approaches, we conclude that CUCM-36 ((1E,4Z,6E)-1-(3,4-Diphenoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-phenoxyphenyl)-1,4,6-heptatrien-3-one) is the best anti-EGFR compound with high drug-likeness, ADME properties, and low toxicity properties. CUCM-36 compound has demonstrated better affinity towards both wild-type (ΔG is −8.5 kcal/Mol) and mutant forms (V769L & K846R; ΔG for both is >−9.20 kcal/Mol) compared to natural CUCM and Gefitinib inhibitor. This study advises the future laboratory assays to develop CUCM-36 as a novel drug compound for treating EGFR positive non-small cell lung cancer patients. Keywords: Curcumin analogue, EGFR genetic, Molecular docking, Novel compound, Mutations
Keywords	Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Exploring celiac disease candidate pathways by global gene expression profiling and gene network cluster analysis

Babajan Banaganapalli / Haifa Mansour / Arif Mohammed / Arwa Mastoor Alharthi / Nada Mohammed Aljuaid / Khalidah Khalid Nasser / Aftab Ahmad / Omar I. Saadah / Jumana Yousuf Al-Aama / Ramu Elango / Noor Ahmad Shaik

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 13

Abstract: Abstract Celiac disease (CeD) is a gastrointestinal autoimmune disorder, whose specific molecular basis is not yet fully interpreted. Therefore, in this study, we compared the global gene expression profile of duodenum tissues from CeD patients, both at ... ...

Abstract	Abstract Celiac disease (CeD) is a gastrointestinal autoimmune disorder, whose specific molecular basis is not yet fully interpreted. Therefore, in this study, we compared the global gene expression profile of duodenum tissues from CeD patients, both at the time of disease diagnosis and after two years of the gluten-free diet. A series of advanced systems biology approaches like differential gene expression, protein–protein interactions, gene network-cluster analysis were deployed to annotate the candidate pathways relevant to CeD pathogenesis. The duodenum tissues from CeD patients revealed the differential expression of 106 up- and 193 down-regulated genes. The pathway enrichment of differentially expressed genes (DEGs) highlights the involvement of biological pathways related to loss of cell division regulation (cell cycle, p53 signalling pathway), immune system processes (NOD-like receptor signalling pathway, Th1, and Th2 cell differentiation, IL-17 signalling pathway) and impaired metabolism and absorption (mineral and vitamin absorptions and drug metabolism) in celiac disease. The molecular dysfunctions of these 3 biological events tend to increase the number of intraepithelial lymphocytes (IELs) and villous atrophy of the duodenal mucosa promoting the development of CeD. For the first time, this study highlights the involvement of aberrant cell division, immune system, absorption, and metabolism pathways in CeD pathophysiology and presents potential novel therapeutic opportunities.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Novel MYO1D Missense Variant Identified Through Whole Exome Sequencing and Computational Biology Analysis Expands the Spectrum of Causal Genes of Laterality Defects

Rabab Said Alsafwani / Khalidah K. Nasser / Thoraia Shinawi / Babajan Banaganapalli / Hanan Abdelhalim ElSokary / Zhaher F. Zaher / Noor Ahmad Shaik / Gaser Abdelmohsen / Jumana Yousuf Al-Aama / Adam J. Shapiro / Osman O. Al-Radi / Ramu Elango / Turki Alahmadi

Frontiers in Medicine, Vol

2021 Volume 8

Abstract: Laterality defects (LDs) or asymmetrically positioned organs are a group of rare developmental disorders caused by environmental and/or genetic factors. However, the exact molecular pathophysiology of LD is not yet fully characterised. In this context, ... ...

Abstract	Laterality defects (LDs) or asymmetrically positioned organs are a group of rare developmental disorders caused by environmental and/or genetic factors. However, the exact molecular pathophysiology of LD is not yet fully characterised. In this context, studying Arab population presents an ideal opportunity to discover the novel molecular basis of diseases owing to the high rate of consanguinity and genetic disorders. Therefore, in the present study, we studied the molecular basis of LD in Arab patients, using next-generation sequencing method. We discovered an extremely rare novel missense variant in MYO1D gene (Pro765Ser) presenting with visceral heterotaxy and left isomerism with polysplenia syndrome. The proband in this index family has inherited this homozygous variant from her heterozygous parents following the autosomal recessive pattern. This is the first report to show MYO1D genetic variant causing left–right axis defects in humans, besides previous known evidence from zebrafish, frog and Drosophila models. Moreover, our multilevel bioinformatics-based structural (protein variant structural modelling, divergence, and stability) analysis has suggested that Ser765 causes minor structural drifts and stability changes, potentially affecting the biophysical and functional properties of MYO1D protein like calmodulin binding and microfilament motor activities. Functional bioinformatics analysis has shown that MYO1D is ubiquitously expressed across several human tissues and is reported to induce severe phenotypes in knockout mouse models. In conclusion, our findings show the expanded genetic spectrum of LD, which could potentially pave way for the novel drug target identification and development of personalised medicine for high-risk families.
Keywords	laterality defects ; whole exome sequencing ; microfilament ; gene expression ; variant ; Medicine (General) ; R5-920
Subject code	572
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: In-silico analysis of inflammatory bowel disease (IBD) GWAS loci to novel connections.

Md Mesbah-Uddin / Ramu Elango / Babajan Banaganapalli / Noor Ahmad Shaik / Fahad A Al-Abbasi

PLoS ONE, Vol 10, Iss 3, p e

2015 Volume 0119420

Abstract: Genome-wide association studies (GWASs) for many complex diseases, including inflammatory bowel disease (IBD), produced hundreds of disease-associated loci-the majority of which are noncoding. The number of GWAS loci is increasing very rapidly, but the ... ...

Abstract	Genome-wide association studies (GWASs) for many complex diseases, including inflammatory bowel disease (IBD), produced hundreds of disease-associated loci-the majority of which are noncoding. The number of GWAS loci is increasing very rapidly, but the process of translating single nucleotide polymorphisms (SNPs) from these loci to genomic medicine is lagging. In this study, we investigated 4,734 variants from 152 IBD associated GWAS loci (IBD associated 152 lead noncoding SNPs identified from pooled GWAS results + 4,582 variants in strong linkage-disequilibrium (LD) (r2 ≥0.8) for EUR population of 1K Genomes Project) using four publicly available bioinformatics tools, e.g. dbPSHP, CADD, GWAVA, and RegulomeDB, to annotate and prioritize putative regulatory variants. Of the 152 lead noncoding SNPs, around 11% are under strong negative selection (GERP++ RS ≥2); and ~30% are under balancing selection (Tajima's D score >2) in CEU population (1K Genomes Project)--though these regions are positively selected (GERP++ RS <0) in mammalian evolution. The analysis of 4,734 variants using three integrative annotation tools produced 929 putative functional SNPs, of which 18 SNPs (from 15 GWAS loci) are in concordance with all three classifiers. These prioritized noncoding SNPs may contribute to IBD pathogenesis by dysregulating the expression of nearby genes. This study showed the usefulness of integrative annotation for prioritizing fewer functional variants from a large number of GWAS markers.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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