The best from both disciplines: integrating human and microbial signatures from whole genome sequencing to advance cancer diagnostics.

Liquid biopsies are transforming oncology, enabling earlier diagnosis, dynamic treatment guidance, and personalized precision medicine, yet current approaches focusing mainly on circulating host cell-free DNA (cfDNA) neglect crucial information within co-existing microbial cell-free DNA (mcfDNA). This review argues for the combined potential of simultaneously analyzing host and microbial signals from samples like blood, specifically focusing on circulating tumor DNA (ctDNA) as the key host component. While ctDNA analysis is already used to guide treatment decisions, the detection of mcfDNA-although present in smaller amounts compared to total cfDNA-offers a distinct and complementary opportunity to identify disease-causing microbes and investigate the host-associated microbiome in the context of cancer. Leveraging machine learning strategies is essential to integrate these multi-view data sets and realize their full potential for enhancing liquid biopsy applications, particularly in early cancer detection.