GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota Transplantation Analysis.
GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota Transplantation Analysis.
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DOI：
10.1371/journal.pone.0158897
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Miller SI
中科院分区：
文献类型：
--
作者：
Brittnacher MJ;Heltshe SL;Hayden HS;Radey MC;Weiss EJ;Damman CJ;Zisman TL;Suskind DL;Miller SI
在人类疾病的临床研究中，肠道微生物群的比较分析通常依赖于对物种或基因的识别和量化。除了探索微生物组的特定功能特征和物种多样性或扩张的潜在意义外，还计算微生物组相似性，以研究针对改变微生物组的治疗措施的变化。已建立的生态相似性度量可以从物种丰富度来构建，但缺乏直接从全基因组鸟枪(WGS)元基因组序列计算这些常用的生态学相似性度量的方法。我们提出了一种计算WGS元基因组序列相似性的无比对方法，该方法类似于物种的Bray-Curtis指数，由通用序列相似性测试工具(GUTSS)软件应用程序实现。这一方法被应用于健康幼儿的肠道微生物群，以测量在生命的前3年向成人微生物群的发育变化。我们还计算了供体和受体微生物群的相似性，以衡量粪便微生物区系移植(FMT)研究中供体微生物区系的建立或植入，这些研究侧重于轻到中度的克罗恩病。我们展示了如何计算与供体的相对相似指数，作为患者微生物群对FMT反应的变化的衡量标准。由于如果没有量化实际FMT植入的分析方法，就不能完全评估移植过程的临床效果，因此我们开发了一种检测肠道微生物群变化的方法，该方法独立于物种鉴定和数据库偏见，对微生物成分的相对丰度变化敏感，并可作为移植成功与临床疾病测量相关联的指数。更广泛地说，这种方法可以应用于临床评估人类微生物群，并为可能针对微生物组改变的特定疗法的候选个体提供潜在的诊断判断。
Comparative analysis of gut microbiomes in clinical studies of human diseases typically rely on identification and quantification of species or genes. In addition to exploring specific functional characteristics of the microbiome and potential significance of species diversity or expansion, microbiome similarity is also calculated to study change in response to therapies directed at altering the microbiome. Established ecological measures of similarity can be constructed from species abundances, however methods for calculating these commonly used ecological measures of similarity directly from whole genome shotgun (WGS) metagenomic sequence are lacking. We present an alignment-free method for calculating similarity of WGS metagenomic sequences that is analogous to the Bray–Curtis index for species, implemented by the General Utility for Testing Sequence Similarity (GUTSS) software application. This method was applied to intestinal microbiomes of healthy young children to measure developmental changes toward an adult microbiome during the first 3 years of life. We also calculate similarity of donor and recipient microbiomes to measure establishment, or engraftment, of donor microbiota in fecal microbiota transplantation (FMT) studies focused on mild to moderate Crohn's disease. We show how a relative index of similarity to donor can be calculated as a measure of change in a patient's microbiome toward that of the donor in response to FMT. Because clinical efficacy of the transplant procedure cannot be fully evaluated without analysis methods to quantify actual FMT engraftment, we developed a method for detecting change in the gut microbiome that is independent of species identification and database bias, sensitive to changes in relative abundance of the microbial constituents, and can be formulated as an index for correlating engraftment success with clinical measures of disease. More generally, this method may be applied to clinical evaluation of human microbiomes and provide potential diagnostic determination of individuals who may be candidates for specific therapies directed at alteration of the microbiome.