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 ...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.展开更多
As a supplementary of [Xu L. Front. Electr. Electron. Eng. China, 2010, 5（3）： 281-328], this paper outlines current status of efforts made on Bayesian Ying- Yang （BYY） harmony learning, plus gene analysis appli- ...As a supplementary of [Xu L. Front. Electr. Electron. Eng. China, 2010, 5（3）： 281-328], this paper outlines current status of efforts made on Bayesian Ying- Yang （BYY） harmony learning, plus gene analysis appli- cations. At the beginning, a bird＇s-eye view is provided via Gaussian mixture in comparison with typical learn- ing algorithms and model selection criteria. Particularly, semi-supervised learning is covered simply via choosing a scalar parameter. Then, essential topics and demand- ing issues about BYY system design and BYY harmony learning are systematically outlined, with a modern per- spective on Yin-Yang viewpoint discussed, another Yang factorization addressed, and coordinations across and within Ying-Yang summarized. The BYY system acts as a unified framework to accommodate unsupervised, su- pervised, and semi-supervised learning all in one formu- lation, while the best harmony learning provides novelty and strength to automatic model selection. Also, mathe- matical formulation of harmony functional has been ad- dressed as a unified scheme for measuring the proximity to be considered in a BYY system, and used as the best choice among others. Moreover, efforts are made on a number of learning tasks, including a mode-switching factor analysis proposed as a semi-blind learning frame- work for several types of independent factor analysis, a hidden Markov model （HMM） gated temporal fac- tor analysis suggested for modeling piecewise stationary temporal dependence, and a two-level hierarchical Gaus- sian mixture extended to cover semi-supervised learning, as well as a manifold learning modified to facilitate au- tomatic model selection. Finally, studies are applied to the problems of gene analysis, such as genome-wide asso- ciation, exome sequencing analysis, and gene transcrip- tional regulation.展开更多
文摘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.
文摘As a supplementary of [Xu L. Front. Electr. Electron. Eng. China, 2010, 5（3）： 281-328], this paper outlines current status of efforts made on Bayesian Ying- Yang （BYY） harmony learning, plus gene analysis appli- cations. At the beginning, a bird＇s-eye view is provided via Gaussian mixture in comparison with typical learn- ing algorithms and model selection criteria. Particularly, semi-supervised learning is covered simply via choosing a scalar parameter. Then, essential topics and demand- ing issues about BYY system design and BYY harmony learning are systematically outlined, with a modern per- spective on Yin-Yang viewpoint discussed, another Yang factorization addressed, and coordinations across and within Ying-Yang summarized. The BYY system acts as a unified framework to accommodate unsupervised, su- pervised, and semi-supervised learning all in one formu- lation, while the best harmony learning provides novelty and strength to automatic model selection. Also, mathe- matical formulation of harmony functional has been ad- dressed as a unified scheme for measuring the proximity to be considered in a BYY system, and used as the best choice among others. Moreover, efforts are made on a number of learning tasks, including a mode-switching factor analysis proposed as a semi-blind learning frame- work for several types of independent factor analysis, a hidden Markov model （HMM） gated temporal fac- tor analysis suggested for modeling piecewise stationary temporal dependence, and a two-level hierarchical Gaus- sian mixture extended to cover semi-supervised learning, as well as a manifold learning modified to facilitate au- tomatic model selection. Finally, studies are applied to the problems of gene analysis, such as genome-wide asso- ciation, exome sequencing analysis, and gene transcrip- tional regulation.
