Assigning roles to DNA regulatory motifs using comparative genomics.
Assigning roles to DNA regulatory motifs using comparative genomics.
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DOI：
10.1093/bioinformatics/btq049
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发表时间：
2010-04-01
期刊：
影响因子：
--
通讯作者：
Bailey TL
中科院分区：
文献类型：
--
作者：
Buske FA;Bodén M;Bauer DC;Bailey TL
动机：转录因子在细胞的整个生命周期中起着至关重要的作用。它们的功能角色是由它们调控的基因决定的。揭示这些角色不仅有助于了解手头的工作组，还可以将其置于整个监管网络的背景下。结果：在这里，我们提出了一种对齐和无阈值的比较基因组学方法来分配DNA调控基序的功能角色。我们将我们的方法引入GOMO算法，这是一种计算工具，用于检测用户指定的DNA调控基序[表示为位置权重矩阵(PWM)]和基因本体论(GO)术语之间的关联。将多个物种纳入分析大大提高了GOMO识别与TFS监管目标相关的GO术语的能力。在预测酿酒酵母和智人Tf角色的过程中，包括三个比较物种，显著预测的数量分别增加了75%和200%。预测的围棋术语也更加具体，从而对TF的作用产生了更深入的生物学见解。调整单个序列组成的基序(结合)亲和力分数被证明是避免假阳性关联的关键。我们描述了一种新的DNA序列评分算法，该算法补偿了单个序列碱基组成的DNA结合亲和力的热力学测量。事实证明，GOMO的预测精度对如何定义推动者相对不敏感。因为GOMO使用了一种无阈值的基因集分析形式，所以没有自由的参数可以调整。生物学家可以通过网络(http://meme.nbcr.net).)使用GOMO来研究感兴趣的DNA调控基序的潜在作用联系人：t.bailey@uq.edu.au补充信息：补充数据可从BioInformation Online获得。
Motivation: Transcription factors (TFs) are crucial during the lifetime of the cell. Their functional roles are defined by the genes they regulate. Uncovering these roles not only sheds light on the TF at hand but puts it into the context of the complete regulatory network. Results: Here, we present an alignment- and threshold-free comparative genomics approach for assigning functional roles to DNA regulatory motifs. We incorporate our approach into the Gomo algorithm, a computational tool for detecting associations between a user-specified DNA regulatory motif [expressed as a position weight matrix (PWM)] and Gene Ontology (GO) terms. Incorporating multiple species into the analysis significantly improves Gomo's ability to identify GO terms associated with the regulatory targets of TFs. Including three comparative species in the process of predicting TF roles in Saccharomyces cerevisiae and Homo sapiens increases the number of significant predictions by 75 and 200%, respectively. The predicted GO terms are also more specific, yielding deeper biological insight into the role of the TF. Adjusting motif (binding) affinity scores for individual sequence composition proves to be essential for avoiding false positive associations. We describe a novel DNA sequence-scoring algorithm that compensates a thermodynamic measure of DNA-binding affinity for individual sequence base composition. Gomo's prediction accuracy proves to be relatively insensitive to how promoters are defined. Because Gomo uses a threshold-free form of gene set analysis, there are no free parameters to tune. Biologists can investigate the potential roles of DNA regulatory motifs of interest using Gomo via the web (http://meme.nbcr.net). Contact: t.bailey@uq.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.
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DOI：
10.1016/s0097-8485(96)80004-0
发表时间：
1996-03-01
期刊：
COMPUTERS & CHEMISTRY
影响因子：
--
作者：
Gribskov, M;Robinson, NL
通讯作者：
Robinson, NL
DOI：
10.1111/j.1467-9868.2004.00439.x
发表时间：
2004-01-01
影响因子：
5.8
作者：
Storey, JD;Taylor, JE;Siegmund, D
通讯作者：
Siegmund, D
影响因子：
14.8
作者：
Berger, Michael F.;Bulyk, Martha L.
通讯作者：
Bulyk, Martha L.
影响因子：
14.9
作者：
Roven, C;Bussemaker, HJ
通讯作者：
Bussemaker, HJ
影响因子：
64.8
作者：
Kellis, M;Patterson, N;Lander, ES
通讯作者：
Lander, ES