New bioinformatics approach to analyze gene expressions and signaling pathways reveals unique purine gene dysregulation profiles that distinguish between CD and UC.
New bioinformatics approach to analyze gene expressions and signaling pathways reveals unique purine gene dysregulation profiles that distinguish between CD and UC.
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DOI：
10.1002/ibd.20893
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发表时间：
2009-07
影响因子：
4.9
通讯作者：
Christofi, Fievos L.
中科院分区：
文献类型：
--
作者：
Rybaczyk, Leszek;Rozmiarek, Andrew;Circle, Kristin;Grants, Iveta;Needleman, Bradley;Wunderlich, Jacqueline E.;Huang, Kun;Christofi, Fievos L.
关键词：
嘌呤基因的表达受到炎症或实验性结肠炎的调节，并且改变的表达导致肠道功能中断。我们研究了IBD中嘌呤基因的失调谱，并使用通路分析和新的基因表达和选择比较分析（CAGES）方法确定它们是否可以区分CD和UC。通过NCI BRB阵列工具分析来自NCBI GEO（http：//www.example.com projects /geo/）的22个嘌呤基因和36个探针组的原始数据集，www.ncbi.nlm.nih.gov/ IBD中59%的嘌呤基因发生失调，包括AD 0 RA 3、CD 73、AD 0 RA 2A、AD 0 RA 2B、阿达尔、AMPD 2、AMPD 3、DPP 4、P2 RY 5、P2 RY 6、P2 RY 13、P2 RY 14和P2 RX 5。在CD活检组织中，ADORA 3、AMPD 3、P2 RY 13和P2 RY 5的表达与急性炎症评分、CDAI或疾病慢性化呈负相关;在UC中，P2 RY 14的表达呈正相关。在粘膜活检或PBMC中，CD和UC通过嘌呤基因的独特失调模式（上调或下调）来区分。对于每种疾病，嘌呤基因失调在PBMC和活检之间不同，并且可能在性别之间不同。免疫途径分析（IPA）显示，CD 73（上调）或ADORA 3（下调）表达的改变与炎症或嘌呤基因（≤ 57个基因的10%）以及GPCR、cAMP依赖性和炎症途径之间存在显著相关性; IPA可区分CD和UC。总之，CAGES和通路分析提供了新的证据，表明UC和CD具有与炎症、cAMP或其他信号通路相关的不同嘌呤基因失调特征。疾病特异性嘌呤基因特征谱和途径关联可能具有治疗、诊断和功能相关性。
Expression of purine genes is modulated by inflammation or experimental colitis and altered expression leads to disrupted gut function. We studied purine gene dysregulation profiles in IBD and determined whether they can distinguish between CD and UC using Pathway Analysis and a new Comparative Analysis of Gene Expression and Selection (CAGES) method. Raw datasets for 22 purine genes and 36 probe-sets from NCBI GEO (http://www.ncbi.nlm.nih.gov/ projects /geo/) were analyzed by NCI BRB array tools for random-variance of multiple/36 t-tests in colonic mucosal biopsies or PBMCs of CD, UC or control subjects. Dysregulation occurs in 59% of purine genes in IBD including ADORA3,CD73, ADORA2A,ADORA2B,ADAR,AMPD2,AMPD3,DPP4, P2RY5,P2RY6,P2RY13,P2RY14 and P2RX5. In CD biopsies, expression of ADORA3,AMPD3,P2RY13 and P2RY5 were negatively correlated with acute inflammatory score, CDAI or disease chronicity;P2RY14 was positively correlated in UC. In mucosal biopsies or PBMCs, CD and UC were distinguished by unique patterns of dysregulation (up- or down-regulation) in purine genes. Purine gene dysregulation differs between PBMCs and biopsies and possibly between sexes for each disease. Ingenuity pathway analysis (IPA) revealed significant associations between alterations in the expression of CD73 (upregulation) or ADORA3 (downregulation) and inflammatory or purine genes (≤10% of 57 genes) as well as GPCR, cAMP-dependent and inflammatory pathways; IPA distinguishes CD from UC. In conclusion, CAGES and Pathway Analysis provided novel evidence that UC and CD have distinct purine gene dysregulation signatures in association with inflammation, cAMP or other signaling pathways. Disease-specific purine gene signature profiles and pathway associations may be of therapeutic, diagnostic and functional relevance.
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影响因子：
3.1
作者：
Cavalcante, IC;Castro, MV;Brito, GAC
通讯作者：
Brito, GAC
影响因子：
13.8
作者：
DRAGUNOW, M;FAULL, RLM
通讯作者：
FAULL, RLM
影响因子：
4.9
作者：
Antonioli, L;Fornai, M;Del Tacca, M
通讯作者：
Del Tacca, M
影响因子：
29.4
作者：
Christofi, FL;Kim, M;Cooke, HJ
通讯作者：
Cooke, HJ
DOI：
10.1152/ajpgi.1999.276.2.g451
发表时间：
1999-02-01
影响因子：
4.5
作者：
Cooke, HJ;Wang, YZ;Christofi, FL
通讯作者：
Christofi, FL