Robust prediction of colorectal cancer via gut microbiome 16S rRNA sequencing data.

Annamaria Porreca, Eliana Ibrahimi, Fabrizio Maturo, Laura Judith Marcos Zambrano, Melisa Meto, Marta B Lopes
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Abstract

Introduction. The study addresses the challenge of utilizing human gut microbiome data for the early detection of colorectal cancer (CRC). The research emphasizes the potential of using machine learning techniques to analyze complex microbiome datasets, providing a non-invasive approach to identifying CRC-related microbial markers.Hypothesis/Gap Statement. The primary hypothesis is that a robust machine learning-based analysis of 16S rRNA microbiome data can identify specific microbial features that serve as effective biomarkers for CRC detection, overcoming the limitations of classical statistical models in high-dimensional settings.Aim. The primary objective of this study is to explore and validate the potential of the human microbiome, specifically in the colon, as a valuable source of biomarkers for colorectal cancer (CRC) detection and progression. The focus is on developing a classifier that effectively predicts the presence of CRC and normal samples based on the analysis of three previously published faecal 16S rRNA sequencing datasets.Methodology. To achieve the aim, various machine learning techniques are employed, including random forest (RF), recursive feature elimination (RFE) and a robust correlation-based technique known as the fuzzy forest (FF). The study utilizes these methods to analyse the three datasets, comparing their performance in predicting CRC and normal samples. The emphasis is on identifying the most relevant microbial features (taxa) associated with CRC development via partial dependence plots, i.e. a machine learning tool focused on explainability, visualizing how a feature influences the predicted outcome.Results. The analysis of the three faecal 16S rRNA sequencing datasets reveals the consistent and superior predictive performance of the FF compared to the RF and RFE. Notably, FF proves effective in addressing the correlation problem when assessing the importance of microbial taxa in explaining the development of CRC. The results highlight the potential of the human microbiome as a non-invasive means to detect CRC and underscore the significance of employing FF for improved predictive accuracy.Conclusion. In conclusion, this study underscores the limitations of classical statistical techniques in handling high-dimensional information such as human microbiome data. The research demonstrates the potential of the human microbiome, specifically in the colon, as a valuable source of biomarkers for CRC detection. Applying machine learning techniques, particularly the FF, is a promising approach for building a classifier to predict CRC and normal samples. The findings advocate for integrating FF to overcome the challenges associated with correlation when identifying crucial microbial features linked to CRC development.

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通过肠道微生物组 16S rRNA 测序数据对结直肠癌进行可靠预测。
简介该研究探讨了利用人类肠道微生物组数据进行结直肠癌(CRC)早期检测所面临的挑战。研究强调了使用机器学习技术分析复杂微生物组数据集的潜力,提供了一种非侵入性方法来识别与 CRC 相关的微生物标记物。主要假设是,对 16S rRNA 微生物组数据进行基于机器学习的稳健分析,可以识别特定的微生物特征,作为检测 CRC 的有效生物标记物,克服经典统计模型在高维环境中的局限性。本研究的主要目的是探索和验证人类微生物组(尤其是结肠中的微生物组)作为结直肠癌(CRC)检测和进展的生物标志物的潜力。研究重点是在分析之前发表的三个粪便 16S rRNA 测序数据集的基础上,开发一种能有效预测 CRC 和正常样本的分类器。为实现这一目标,研究人员采用了多种机器学习技术,包括随机森林(RF)、递归特征消除(RFE)和一种称为模糊森林(FF)的稳健相关技术。研究利用这些方法分析了三个数据集,比较了它们在预测 CRC 和正常样本方面的性能。重点是通过部分依存图(即一种注重可解释性的机器学习工具)确定与 CRC 发展最相关的微生物特征(类群),直观显示特征如何影响预测结果。对三个粪便 16S rRNA 测序数据集的分析表明,与 RF 和 RFE 相比,FF 具有一致且更优越的预测性能。值得注意的是,在评估微生物类群对解释 CRC 发病的重要性时,FF 能有效解决相关性问题。研究结果凸显了人类微生物组作为一种非侵入性手段检测 CRC 的潜力,并强调了采用 FF 提高预测准确性的重要性。总之,本研究强调了经典统计技术在处理人类微生物组数据等高维信息时的局限性。研究表明,人类微生物组,特别是结肠中的微生物组,有可能成为检测 CRC 的重要生物标志物来源。应用机器学习技术,特别是 FF,是建立预测 CRC 和正常样本的分类器的有效方法。研究结果主张在确定与 CRC 发展相关的关键微生物特征时,整合 FF 以克服相关性带来的挑战。
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