在网络中对上下文相关的癌症基因特征进行优先级排序。
Prioritizing Context-Dependent Cancer Gene Signatures in Networks.
作者信息
Capobianco Enrico, Lisse Thomas S, Rieger Sandra
机构信息
NUDDHA LLC, Lake Worth, FL 33463, USA.
Avantyx Pharmaceuticals, Miami, FL 33136, USA.
出版信息
Cancers (Basel). 2025 Jan 3;17(1):136. doi: 10.3390/cancers17010136.
There are numerous ways of portraying cancer complexity based on combining multiple types of data. A common approach involves developing signatures from gene expression profiles to highlight a few key reproducible features that provide insight into cancer risk, progression, or recurrence. Normally, a selection of such features is made through relevance or significance, given a reference context. In the case of highly metastatic cancers, numerous gene signatures have been published with varying levels of validation. Then, integrating the signatures could potentially lead to a more comprehensive view of the connection between cancer and its phenotypes by covering annotations not fully explored in individual studies. This broader understanding of disease phenotypes would improve the predictive accuracy of statistical models used to identify meaningful associations. We present an example of this approach by reconciling a great number of published signatures into meta-signatures relevant to Osteosarcoma (OS) metastasis. We generate a well-annotated and interpretable interactome network from integrated OS gene expression signatures and identify key nodes that regulate essential aspects of metastasis. While the connected signatures link diverse prognostic measurements for OS, the proposed approach is applicable to any type of cancer.
基于整合多种类型的数据,有多种描绘癌症复杂性的方法。一种常见的方法是从基因表达谱中开发特征标志物,以突出一些关键的可重复特征,这些特征有助于深入了解癌症风险、进展或复发情况。通常,在给定参考背景的情况下,通过相关性或显著性来选择此类特征。在高转移性癌症的情况下,已经发表了许多具有不同验证水平的基因特征标志物。然后,整合这些特征标志物可能会通过涵盖个别研究中未充分探索的注释,从而对癌症与其表型之间的联系形成更全面的认识。对疾病表型的这种更广泛理解将提高用于识别有意义关联的统计模型的预测准确性。我们通过将大量已发表的特征标志物整合为与骨肉瘤(OS)转移相关的元特征标志物,展示了这种方法的一个示例。我们从整合的OS基因表达特征标志物中生成一个注释良好且可解释的相互作用组网络,并识别调节转移关键方面的关键节点。虽然这些相关的特征标志物将OS的各种预后测量联系起来,但所提出的方法适用于任何类型的癌症。