摘要
Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.
Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.
作者
Dago Dougba Noel
Koffi N’Guessan Bénédicte Sonia
Dagnogo Olefongo
Daramcoum Wentoin Alimata Marie-Pierre
Mauro Giacomelli
Dagnogo Dramane
Eboulé Ago Eliane Rebecca
Yao Saraka Didier Martial
Diarrassouba Nafan
Giovanni Malerba
Raffaele Badolato
Dago Dougba Noel;Koffi N’Guessan Bénédicte Sonia;Dagnogo Olefongo;Daramcoum Wentoin Alimata Marie-Pierre;Mauro Giacomelli;Dagnogo Dramane;Eboulé Ago Eliane Rebecca;Yao Saraka Didier Martial;Diarrassouba Nafan;Giovanni Malerba;Raffaele Badolato(Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy;Angelo Nocivelli Institute of Molecular Medicine, Childrens Hospital, ASST Spedali Civili, Brescia, Italy;Unit of Biostatistics and Biomathematics & Unit of Bioinformatics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy;Biological Sciences Training and Research Unit, Department of Genetic and Biochemistry, Peleforo Gon Coulibaly University, Korhogo, Cte dIvoire;Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy;Biosciences Training and Research Unit, Biology and Health Laboratory, Felix Houphouet-Boigny University, Abidjan, Cte dIvoire)
