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运用 Gurobi 优化器,通过数学线性规划对 miRNA 介导的基因调控进行建模。

Mathematical Linear Programming to Model MicroRNAs-Mediated Gene Regulation Using Gurobi Optimizer.

机构信息

Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.

出版信息

Methods Mol Biol. 2021;2328:287-301. doi: 10.1007/978-1-0716-1534-8_19.

Abstract

Genes are transcribed into various RNA molecules, and a portion of them called messenger RNA (mRNA) is then translated into proteins in the process known as gene expression. Gene expression is a high-energy demanding process, and aberrant expression changes often manifest into pathophysiology. Therefore, gene expression is tightly regulated by several factors at different levels. MicroRNAs (miRNAs) are one of the powerful post-transcriptional regulators involved in key biological processes and diseases. They inhibit the translation of their mRNA targets or degrade them in a sequence-specific manner, and hence control the rate of protein synthesis. In recent years, in response to experimental limitations, several computational methods have been proposed to predict miRNA target genes based on sequence complementarity and structural features. However, these predictions yield a large number of false positives. Integration of gene and miRNA expression data drastically alleviates this problem. Here, I describe a mathematical linear modeling approach to identify miRNA targets at the genome scale using gene and miRNA expression data. Mathematical modeling is faster and more scalable to genome-level compared to conventional statistical modeling approaches.

摘要

基因被转录成各种 RNA 分子,其中一部分称为信使 RNA(mRNA),然后在基因表达过程中被翻译成蛋白质。基因表达是一个高能量需求的过程,异常的表达变化常常表现为病理生理学。因此,基因表达受到不同层次的几个因素的严格调控。microRNAs(miRNAs)是参与关键生物过程和疾病的强大的转录后调控因子之一。它们以序列特异性的方式抑制其 mRNA 靶标的翻译或降解,从而控制蛋白质合成的速度。近年来,为了应对实验限制,已经提出了几种计算方法,基于序列互补性和结构特征来预测 miRNA 靶基因。然而,这些预测会产生大量的假阳性。整合基因和 miRNA 表达数据可以极大地缓解这个问题。在这里,我描述了一种使用基因和 miRNA 表达数据在基因组范围内识别 miRNA 靶标的数学线性建模方法。与传统的统计建模方法相比,数学建模在基因组水平上更快、更具可扩展性。

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