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单细胞测序在多组学中的应用。

Applications of Single-Cell Sequencing for Multiomics.

作者信息

Xu Yungang, Zhou Xiaobo

机构信息

Center for Systems Medicine, School of Biomedical Informatics, UTHealth at Houston, Houston, TX, USA.

Center for Bioinformatics and Systems Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

出版信息

Methods Mol Biol. 2018;1754:327-374. doi: 10.1007/978-1-4939-7717-8_19.

Abstract

Single-cell sequencing interrogates the sequence or chromatin information from individual cells with advanced next-generation sequencing technologies. It provides a higher resolution of cellular differences and a better understanding of the underlying genetic and epigenetic mechanisms of an individual cell in the context of its survival and adaptation to microenvironment. However, it is more challenging to perform single-cell sequencing and downstream data analysis, owing to the minimal amount of starting materials, sample loss, and contamination. In addition, due to the picogram level of the amount of nucleic acids used, heavy amplification is often needed during sample preparation of single-cell sequencing, resulting in the uneven coverage, noise, and inaccurate quantification of sequencing data. All these unique properties raise challenges in and thus high demands for computational methods that specifically fit single-cell sequencing data. We here comprehensively survey the current strategies and challenges for multiple single-cell sequencing, including single-cell transcriptome, genome, and epigenome, beginning with a brief introduction to multiple sequencing techniques for single cells.

摘要

单细胞测序利用先进的下一代测序技术检测单个细胞的序列或染色质信息。它能提供更高分辨率的细胞差异,有助于在个体细胞的存活和对微环境的适应背景下,更好地理解其潜在的遗传和表观遗传机制。然而,由于起始材料量极少、样本损失和污染,进行单细胞测序及下游数据分析更具挑战性。此外,由于单细胞测序样本制备过程中使用的核酸量处于皮克水平,通常需要大量扩增,这导致测序数据覆盖不均、存在噪声且定量不准确。所有这些独特特性给专门适用于单细胞测序数据的计算方法带来了挑战,因此也对其提出了很高的要求。我们在此全面综述了多种单细胞测序(包括单细胞转录组、基因组和表观基因组测序)的当前策略和挑战,并首先简要介绍了多种单细胞测序技术。

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