Physical Science Oncology Center at Penn, University of Pennsylvania, Philadelphia, PA 19104.
Molecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA 19104.
Proc Natl Acad Sci U S A. 2021 Nov 30;118(48). doi: 10.1073/pnas.2112940118.
Physicochemical principles such as stoichiometry and fractal assembly can give rise to characteristic scaling between components that potentially include coexpressed transcripts. For key structural factors within the nucleus and extracellular matrix, we discover specific gene-gene scaling exponents across many of the 32 tumor types in The Cancer Genome Atlas, and we demonstrate utility in predicting patient survival as well as scaling-informed machine learning (SIML). All tumors with adjacent tissue data show cancer-elevated proliferation genes, with some genes scaling with the nuclear filament , including the transcription factor FOXM1 that we show directly regulates SIML shows that such regulated cancers cluster together with longer overall survival than dysregulated cancers, but high and in half of regulated cancers surprisingly predict poor survival, including for liver cancer. is also studied because it too increases in tumors, and a pan-cancer set of fibrosis genes shows substoichiometric scaling with but predicts patient outcome only for liver cancer-unexpectedly being prosurvival. Single-cell RNA-seq data show nontrivial scaling consistent with power laws from bulk RNA and protein analyses, and SIML segregates synthetic from contractile cancer fibroblasts. Our scaling approach thus yields fundamentals-based power laws relatable to survival, gene function, and experiments.
物理化学原理，如化学计量学和分形组装，可以在潜在包括共表达转录本的成分之间产生特征性的比例关系。对于核和细胞外基质中的关键结构因素，我们在癌症基因组图谱中的 32 种肿瘤类型中的许多类型中发现了特定的基因-基因比例指数，并且我们证明了它在预测患者生存以及比例信息机器学习（SIML）方面的实用性。所有具有相邻组织数据的肿瘤都显示出癌症升高的增殖基因，其中一些基因与核丝状体比例相关，包括转录因子 FOXM1，我们直接证明其直接调节 SIML。SIML 表明，与失调的癌症相比，受调节的癌症与更长的总体生存时间聚类在一起，但令人惊讶的是，高和在一半的受调节癌症中预测预后不良，包括肝癌。也被研究，因为它也在肿瘤中增加，并且一组泛癌纤维化基因与但仅预测肝癌的患者预后 - 出乎意料的是，这是促生存的。单细胞 RNA-seq 数据显示与批量 RNA 和蛋白质分析的幂律一致的重要比例关系，并且 SIML 将合成与收缩性癌症成纤维细胞分开。因此，我们的比例方法产生了基于基本原理的与生存、基因功能和实验相关的幂律。
