Prediction of cell type-specific gene modules: Identification and initial characterization of a core set of smooth muscle-specific genes

Prediction of cell type-specific gene modules: Identification and initial characterization of a core set of smooth muscle-specific genes
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DOI:
10.1101/gr.1197303
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发表时间:
2003-08-01
期刊:
影响因子:
7
通讯作者:
Lindahl, P
Lindahl, P
中科院分区:
生物学1区
文献类型:
--
作者:
Nelander, S;Mostad, P;Lindahl, P

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在相同细胞亚群中表达的基因可能构成由共享的顺式调控元件和一组不同的转录因子调控的模块。识别此类单位是细胞分化分子研究的重要切入点。我们开发了一种通用的方法来分类细胞类型特异性基因表达序列标签(EST)的数据,我们优化它的平滑肌细胞(SMC)特异性基因的识别。表达谱来源于小鼠中EST数据的定量分布,并且基因基于其与已知参考基因(在这种情况下为平滑肌肌球蛋白重链)的谱相似性进行分类。大多数(>90%)已知的SMC特异性基因被鉴定,以及新的候选基因。广泛的实验验证证实了候选物的SMC特异性表达,例如,脂肪瘤优选伴侣(LPP)和新型SMC特异性推定单胺氧化酶SMAO。我们的方法在客观的交叉验证比较中表现得比其他计算方法好得多。SMC特异性基因的总数估计接近50个。
Genes that are expressed in the same subset of cells potentially constitute a module regulated by shared cis-regulatory elements and a distinct set of transcription factors. Identifying such units is an important entry point to the molecular study of cell differentiation. We developed a general method to classify cell type-specific genes from expressed sequence tag (EST) data, and we optimized it for identification of smooth muscle cell (SMC)-specific genes. Expression profiles were derived from the quantitative distribution of EST data in mouse, and genes were classified based on their profile similarity to known reference genes, in this case smooth muscle myosin heavy chain. A large majority (>90%) of known SMC-specific genes were identified, together with novel candidates. Extensive experimental validation confirmed SMC-specific expression of candidates, for example, lipoma preferred partner (LPP) and a novel SMC-specific putative monoamine oxidase, SMAO. Our method performed considerably better than other computational methods in an objective cross validation comparison. The total number of SMC-specific genes is estimated to be similar to50.