Ferrari Ivan, De Grossi Federica, Lai Giancarlo, Oliveto Stefania, Deroma Giorgia, Biffo Stefano, Manfrini Nicola
INGM, Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy.
Department of Biosciences, University of Milan, Milan, Italy.
Brief Bioinform. 2024 Nov 22;26(1). doi: 10.1093/bib/bbae635.
Conventional approaches to predict protein involvement in cancer often rely on defining either aberrant mutations at the single-gene level or correlating/anti-correlating transcript levels with patient survival. These approaches are typically conducted independently and focus on one protein at a time, overlooking nucleotide substitutions outside of coding regions or mutational co-occurrences in genes within the same interaction network. Here, we present CancerHubs, a method that integrates unbiased mutational data, clinical outcome predictions and interactomics to define novel cancer-related protein hubs. Through this approach, we identified TGOLN2 as a putative novel broad cancer tumour suppressor and EFTUD2 as a putative novel multiple myeloma oncogene.
预测蛋白质在癌症中作用的传统方法通常依赖于定义单基因水平上的异常突变,或者将转录水平与患者生存率进行关联/反关联。这些方法通常是独立进行的,每次只关注一种蛋白质,而忽略了编码区域以外的核苷酸替换或同一相互作用网络内基因中的共突变情况。在这里,我们提出了CancerHubs,这是一种整合无偏突变数据、临床结果预测和相互作用组学来定义新型癌症相关蛋白质枢纽的方法。通过这种方法,我们将TGOLN2鉴定为一种推定的新型广泛癌症肿瘤抑制因子,将EFTUD2鉴定为一种推定的新型多发性骨髓瘤癌基因。