logistic矩阵分解法预测临床前癌细胞的临床药物反应。

IF 0.9 4区 生物学 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY
Akram Emdadi, Changiz Eslahchi
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引用次数: 0

摘要

利用大量抗癌药物的癌细胞系药物反应值预测肿瘤药物反应是个体化医疗的重大挑战。通过从临床前模型获得的数据预测患者对药物的反应,由于对细胞系和药物的不同知识的可用性,使得预测患者对药物的反应变得更加容易。本文提出了TCLMF方法,这是一种基于logistic矩阵分解方法,在临床前样本上训练的预测肿瘤样本药物反应的预测模型。TCLMF模型是基于来自癌细胞系的基因表达谱、组织类型信息、药物化学结构和药物敏感性(IC 50)数据设计的。我们使用来自癌症药物敏感性基因组数据集(GDSC)的临床前数据来训练所提出的药物反应模型,然后我们使用该模型来预测来自癌症基因组图谱(TCGA)数据集的样本的药物敏感性。TCLMF方法侧重于识别细胞系和药物的成功特征,以计算肿瘤样本对药物敏感的概率。在本研究中,使用肿瘤样本和细胞系之间的相似性描述来计算每个肿瘤样本的最近细胞系邻居。对新肿瘤的药物反应,然后通过平均从其邻近细胞系获得的低秩特征来计算。我们将TCLMF模型的结果与之前提出的方法的结果进行比较,使用两个数据库和两种方法来测试模型的性能。在第一种方法中,研究了之前方法中考虑的12种已知临床药物反应足够的药物。对于12种药物中的7种,TCLMF可以显著区分对这些药物耐药的患者和对这些药物敏感的患者。在第二种方法中使用阈值将这些方法转换为分类模型,并对结果进行比较。结果表明,TCLMF方法在其他算法的结果之间提供了准确的预测。最后,利用TCLMF的logistic矩阵分解过程得到的潜伏载体,对肿瘤组织类型进行准确分类。这些发现表明,TCLMF方法产生了有效的肿瘤样本潜伏载体。TCLMF方法的源代码可在https://github.com/emdadi/TCLMF中获得。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinical drug response prediction from preclinical cancer cell lines by logistic matrix factorization approach.

Predicting tumor drug response using cancer cell line drug response values for a large number of anti-cancer drugs is a significant challenge in personalized medicine. Predicting patient response to drugs from data obtained from preclinical models is made easier by the availability of different knowledge on cell lines and drugs. This paper proposes the TCLMF method, a predictive model for predicting drug response in tumor samples that was trained on preclinical samples and is based on the logistic matrix factorization approach. The TCLMF model is designed based on gene expression profiles, tissue type information, the chemical structure of drugs and drug sensitivity (IC 50) data from cancer cell lines. We use preclinical data from the Genomics of Drug Sensitivity in Cancer dataset (GDSC) to train the proposed drug response model, which we then use to predict drug sensitivity of samples from the Cancer Genome Atlas (TCGA) dataset. The TCLMF approach focuses on identifying successful features of cell lines and drugs in order to calculate the probability of the tumor samples being sensitive to drugs. The closest cell line neighbours for each tumor sample are calculated using a description of similarity between tumor samples and cell lines in this study. The drug response for a new tumor is then calculated by averaging the low-rank features obtained from its neighboring cell lines. We compare the results of the TCLMF model with the results of the previously proposed methods using two databases and two approaches to test the model's performance. In the first approach, 12 drugs with enough known clinical drug response, considered in previous methods, are studied. For 7 drugs out of 12, the TCLMF can significantly distinguish between patients that are resistance to these drugs and the patients that are sensitive to them. These approaches are converted to classification models using a threshold in the second approach, and the results are compared. The results demonstrate that the TCLMF method provides accurate predictions across the results of the other algorithms. Finally, we accurately classify tumor tissue type using the latent vectors obtained from TCLMF's logistic matrix factorization process. These findings demonstrate that the TCLMF approach produces effective latent vectors for tumor samples. The source code of the TCLMF method is available in https://github.com/emdadi/TCLMF.

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来源期刊
Journal of Bioinformatics and Computational Biology
Journal of Bioinformatics and Computational Biology MATHEMATICAL & COMPUTATIONAL BIOLOGY-
CiteScore
2.10
自引率
0.00%
发文量
57
期刊介绍: The Journal of Bioinformatics and Computational Biology aims to publish high quality, original research articles, expository tutorial papers and review papers as well as short, critical comments on technical issues associated with the analysis of cellular information. The research papers will be technical presentations of new assertions, discoveries and tools, intended for a narrower specialist community. The tutorials, reviews and critical commentary will be targeted at a broader readership of biologists who are interested in using computers but are not knowledgeable about scientific computing, and equally, computer scientists who have an interest in biology but are not familiar with current thrusts nor the language of biology. Such carefully chosen tutorials and articles should greatly accelerate the rate of entry of these new creative scientists into the field.
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