QColors:从短而不连续的下一代测序读数中重建保守病毒类群的算法。

Q2 Medicine
Austin Huang, Rami Kantor, Allison DeLong, Leeann Schreier, Sorin Istrail
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引用次数: 0

摘要

下一代测序技术最近被用于描述艾滋病病毒感染者体内病毒基因型异质性群体(称为类群)的突变谱。这些信息具有临床意义,因为患者体内艾滋病毒的少数基因亚群可使病毒摆脱免疫反应和抗逆转录病毒疗法等选择压力。然而,从新一代测序读数中重建准物种序列的方法尚未得到广泛应用,仍是一个新兴的研究领域。此外,大多数艾滋病研究方法都集中在 454 测序上,而实际使用的许多新一代测序平台仅限于相对于 454 测序更短的读长。在确定如何以最佳方式解决其他平台的读长限制方面,几乎没有开展任何工作。本文介绍的方法结合了读数差异和读数重叠的图示,以保守的方式确定序列中具有足够变异性的区域,从而分离出准物种序列。在这些容易推断准物种的区域内,我们使用约束编程法,通过冲突图的顶点着色来求解最优的准物种子序列确定方法,这种表示方法也适用于非连续读数的数据,如成对端测序。我们将该方法应用于基于实际患者内克隆 HIV-1 测序数据的模拟,从而展示了该方法的实用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

QColors: an algorithm for conservative viral quasispecies reconstruction from short and non-contiguous next generation sequencing reads.

QColors: an algorithm for conservative viral quasispecies reconstruction from short and non-contiguous next generation sequencing reads.

Next generation sequencing technologies have recently been applied to characterize mutational spectra of the heterogeneous population of viral genotypes (known as a quasispecies) within HIV-infected patients. Such information is clinically relevant because minority genetic subpopulations of HIV within patients enable viral escape from selection pressures such as the immune response and antiretroviral therapy. However, methods for quasispecies sequence reconstruction from next generation sequencing reads are not yet widely used and remains an emerging area of research. Furthermore, the majority of research methodology in HIV has focused on 454 sequencing, while many next-generation sequencing platforms used in practice are limited to shorter read lengths relative to 454 sequencing. Little work has been done in determining how best to address the read length limitations of other platforms. The approach described here incorporates graph representations of both read differences and read overlap to conservatively determine the regions of the sequence with sufficient variability to separate quasispecies sequences. Within these tractable regions of quasispecies inference, we use constraint programming to solve for an optimal quasispecies subsequence determination via vertex coloring of the conflict graph, a representation which also lends itself to data with non-contiguous reads such as paired-end sequencing. We demonstrate the utility of the method by applying it to simulations based on actual intra-patient clonal HIV-1 sequencing data.

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来源期刊
In Silico Biology
In Silico Biology Computer Science-Computational Theory and Mathematics
CiteScore
2.20
自引率
0.00%
发文量
1
期刊介绍: The considerable "algorithmic complexity" of biological systems requires a huge amount of detailed information for their complete description. Although far from being complete, the overwhelming quantity of small pieces of information gathered for all kind of biological systems at the molecular and cellular level requires computational tools to be adequately stored and interpreted. Interpretation of data means to abstract them as much as allowed to provide a systematic, an integrative view of biology. Most of the presently available scientific journals focus either on accumulating more data from elaborate experimental approaches, or on presenting new algorithms for the interpretation of these data. Both approaches are meritorious.
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