title: Identification of altered pathways in Down syndrome-associated congenital heart defects using an individualized pathway aberrance score.
abstract: The aim of this study was to identify disrupted pathways related to Down syndrome (DS), and DS-associated congenital heart defects (DS-CHD). The gene expression profile and pathway data of 10 human DS patients and 5 control samples in E-GEOD-1789 were recruited and analyzed by the individualized pathway aberrance score (iPAS) method, consisting of the data processing, gene-level statistics, pathway-level statistics, and significant measurement steps. The pre-processing step identified 12,493 genes and 1022 pathways (4269 genes). The pathway significant analysis identified eight pathways (adjusted P value <0.1) that differed between the disease and control samples. The cross-presentation of particulate exogenous antigen (phagosomes) and methionine salvage pathways showed the most significant differences among these. The gene expression levels of key pathway genes, such as CYBB and ADI1, were higher in disease samples than in normal controls. Based on our results, we predicted that the cross-presentation of particulate exogenous antigens (phagosomes) and the methionine salvage pathway could be good indicators of DS-CHD.
authors.affiliation: Department of Cardiology, Lanzhou General Hospital of Lanzhou Military Area Command, Lanzhou, Gansu Province, China.
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Lanzhou General Hospital of Lanzhou Military Area Command, Lanzhou, Gansu Province, China.
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Cardiology, Lanzhou General Hospital of Lanzhou Military Area Command, Lanzhou, Gansu Province, China.
authors.forename: W Y
authors.initials: WY
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Lanzhou General Hospital of Lanzhou Military Area Command, Lanzhou, Gansu Province, China.
authors.forename: F J
authors.initials: FJ
authors.lastname: Su
authors.affiliation: Department of Cardiology, Lanzhou General Hospital of Lanzhou Military Area Command, Lanzhou, Gansu Province, China.
authors.forename: Y X
authors.initials: YX
authors.lastname: Zhang
mesh_terms: D016022:Case-Control Studies; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism; D004314:Down Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D053263:Gene Regulatory Networks; D006330:Heart Defects, Congenital / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008715:Methionine / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000235:genetics / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D008715:Methionine; C484693:ADI1 protein, human; D049308:Dioxygenases; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases