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一种用于选择稳健的多重应激生物标志物组合的知识整合策略,用于…… (原文结尾不完整)

A knowledge integration strategy for the selection of a robust multi-stress biomarkers panel for .

作者信息

Huang Yiming, Sinha Nishant, Wipat Anil, Bacardit Jaume

机构信息

Interdisciplinary Computing and Complex BioSystems (ICOS) Group, School of Computing, Newcastle University, UK.

Department of Neurology, Perelman School of Medicine, University of Pennsylvania, USA.

出版信息

Synth Syst Biotechnol. 2022 Dec 13;8(1):97-106. doi: 10.1016/j.synbio.2022.12.001. eCollection 2023 Mar.

Abstract

One challenge in the engineering of biological systems is to be able to recognise the cellular stress states of bacterial hosts, as these stress states can lead to suboptimal growth and lower yields of target products. To enable the design of genetic circuits for reporting or mitigating the stress states, it is important to identify a relatively reduced set of gene biomarkers that can reliably indicate relevant cellular growth states in bacteria. Recent advances in high-throughput omics technologies have enhanced the identification of molecular biomarkers specific states in bacteria, motivating computational methods that can identify robust biomarkers for experimental characterisation and verification. Focused on identifying gene expression biomarkers to sense various stress states in subtilis, this study aimed to design a knowledge integration strategy for the selection of a robust biomarker panel that generalises on external datasets and experiments. We developed a recommendation system that ranks the candidate biomarker panels based on complementary information from machine learning model, gene regulatory network and co-expression network. We identified a recommended biomarker panel showing high stress sensing power for a variety of conditions both in the dataset used for biomarker identification (mean f1-score achieved at 0.99), as well as in a range of independent datasets (mean f1-score achieved at 0.98). We discovered a significant correlation between stress sensing power and evaluation metrics such as the number of associated regulators in a gene regulatory network (GRN) and the number of associated modules in a co-expression network (CEN). GRNs and CENs provide information relevant to the diversity of biological processes encoded by biomarker genes. We demonstrate that quantitatively relating meaningful evaluation metrics with stress sensing power has the potential for recognising biomarkers that show better sensitivity and robustness to an extended set of stress conditions and enable a more reliable biomarker panel selection.

摘要

生物系统工程中的一个挑战是能够识别细菌宿主的细胞应激状态,因为这些应激状态可能导致生长不理想以及目标产物产量降低。为了设计用于报告或减轻应激状态的基因回路,识别一组相对精简的基因生物标志物非常重要,这些标志物能够可靠地指示细菌中的相关细胞生长状态。高通量组学技术的最新进展增强了对细菌特定状态分子生物标志物的识别,这推动了能够识别用于实验表征和验证的稳健生物标志物的计算方法的发展。本研究聚焦于识别基因表达生物标志物以感知枯草芽孢杆菌中的各种应激状态,旨在设计一种知识整合策略,用于选择在外部数据集和实验中具有通用性的稳健生物标志物组。我们开发了一种推荐系统,该系统根据机器学习模型、基因调控网络和共表达网络的互补信息对候选生物标志物组进行排名。我们确定了一个推荐的生物标志物组,该组在用于生物标志物识别的数据集(平均F1分数达到0.99)以及一系列独立数据集中(平均F1分数达到0.98),对各种条件都显示出高应激感知能力。我们发现应激感知能力与评估指标之间存在显著相关性,例如基因调控网络(GRN)中相关调节因子的数量以及共表达网络(CEN)中相关模块的数量。GRN和CEN提供了与生物标志物基因编码的生物过程多样性相关的信息。我们证明,将有意义的评估指标与应激感知能力进行定量关联,有可能识别出对更广泛的应激条件具有更好敏感性和稳健性的生物标志物,并实现更可靠的生物标志物组选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e660/9794971/1e43a6ccc200/gr1.jpg

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