Fig. 1: The Oncology Biomarker Discovery (OncoBird) workflow.

a Patients in clinical trials were treated with (T) two treatment regimens with measured clinical endpoints. Subsequently, their tumours are characterised according to (M) tumour genetic alterations (somatic mutations and copy number alterations) and (S) tumour subtypes. b With this input, OncoBird outlines c the molecular landscape and d the biomarker landscape. For the latter, e somatic alterations are explored for a differential patient prognosis for each treatment arm. f Consecutively, for each treatment arm, subtype-specific biomarkers are derived. g Finally, interactions between treatment arms are examined. The grey shadings indicate the data included in the previous analysis step. Here, this is exemplified in the FIRE-3 clinical trial using Kaplan–Meier plots, including 95% confidence intervals (CI) and summary statistics of the Cox regression models. h RAS mutations are established biomarkers of cetuximab resistance. i Patients with RAS wild-type tumours showed a better prognosis when treated with cetuximab within left-sided tumours compared to right-sided tumours. In addition, j the RAS wild-type subpopulation in left-sided tumours showed benefits when treated with cetuximab compared to bevacizumab.