Computational single-cell methods for predicting cancer risk

Despite recent biotechnological breakthroughs, cancer risk prediction remains a formidable computational and experimental challenge. Addressing it is critical in order to improve prevention, early detection and survival rates. Here, I briefly summarize some key emerging theoretical and computational challenges as well as recent computational advances that promise to help realize the goals of cancer -risk prediction. The focus is on computational strategies based on single -cell data, in particular on bottom -up network modeling approaches that aim to estimate cancer stemness and dedifferentiation at single -cell resolution from a systems -biological perspective. I will describe two promising methods, a tissue and cell -lineage independent one based on the concept of diffusion network entropy, and a tissue and cell -lineage specific one that uses transcription factor regulons. Application of these tools to single -cell and single -nucleus RNA-seq data from stages prior to invasive cancer reveal that they can successfully delineate the heterogeneous inter -cellular cancer -risk landscape, identifying those cells that are more likely to turn cancerous. Bottom -up systems biological modeling of single -cell omic data is a novel computational analysis paradigm that promises to facilitate the development of preventive, early detection and cancer -risk prediction strategies.