论文标题

个性化疾病的代谢分析

Personalized Metabolic Analysis of Diseases

论文作者

Cakmak, Ali, Celik, M. Hasan

论文摘要

在包括癌症在内的许多疾病中,患者细胞的代谢接线发生了巨大改变。了解这种变化的性质可能为新的治疗机会以及针对患者的个性化治疗策略的制定铺平了道路。在本文中,我们提出了一种算法,代谢,该算法允许对疾病状态中细胞生化网络的变化进行系统级别的分析。它可以研究在反应和途径级粒度上的疾病,以详细和总结疾病病因的看法。代谢技术采用了通量变异性分析,其目标函数是基于生物流体代谢组学测量的动态构建的,以个性化的方式。此外,代谢形成了每种疾病的分类模型,以诊断患者并根据计算的代谢网络变化来预测其亚组。我们证明了在三种不同的疾病中使用代谢,即乳腺癌,克罗恩病和大肠癌。我们的结果表明,构建的监督学习模型成功地通过平均90%的F1评分诊断患者。此外,除了确认先前报道的乳腺癌相关途径外,我们发现丁烷酸盐代谢经历显着降低了活性,而精氨酸和脯氨酸代谢的活性显着增加,这尚未报道。代谢可作为PYTHON包装提供。

The metabolic wiring of patient cells is altered drastically in many diseases, including cancer. Understanding the nature of such changes may pave the way for new therapeutic opportunities, as well as the development of personalized treatment strategies for patients. In this paper, we propose an algorithm, Metabolitics, which allows systems-level analysis of changes in the biochemical network of cells in disease states. It enables the study of a disease at both reaction- and pathway-level granularities for detailed and summarized view of disease etiology. Metabolitics employs flux variability analysis with an objective function which is dynamically built based on the biofluid metabolomics measurements in a personalized manner. Moreover, Metabolitics builds classification models for each disease to diagnose patients and predict their subgroups based on the computed metabolic network changes. We demonstrate the use of Metabolitics on three distinct diseases, namely, breast cancer, Crohn's disease, and colorectal cancer. Our results show that the constructed supervised learning models successfully diagnose patients by f1-score of over 90% on the average. Besides, in addition to the confirmation of previously reported breast cancer associated pathways, we discovered that Butanoate metabolism experiences significantly decreased activity, while Arginine and Proline Metabolism is subject to significant increase in activity, which have not been reported before. Metabolitics is made available as a Python package in pypi.

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