Analysis and Visualization of Longitudinal Genomic and Clinical Data from the AACR Project GENIE Biopharma Collaborative in cBioPortal.

International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data from 19 cancer centers, makes data from >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model. Several thousand of these cases are now also available in cBioPortal. We have significantly enhanced the functionalities of cBioPortal to support the visualization and analysis of this rich clinico-genomic linked dataset, as well as datasets generated by other centers and consortia. Examples of these enhancements include (i) visualization of the longitudinal clinical and genomic data at the patient level, including timelines for diagnoses, treatments, and outcomes; (ii) the ability to select samples based on treatment status, facilitating a comparison of molecular and clinical attributes between samples before and after a specific treatment; and (iii) survival analysis estimates based on individual treatment regimens received. Together, these features provide cBioPortal users with a toolkit to interactively investigate complex clinico-genomic data to generate hypotheses and make discoveries about the impact of specific genomic variants on prognosis and therapeutic sensitivities in cancer. SIGNIFICANCE: Enhanced cBioPortal features allow clinicians and researchers to effectively investigate longitudinal clinico-genomic data from patients with cancer, which will improve exploration of data from the AACR Project GENIE Biopharma Collaborative and similar datasets.

Carotenoid-dependent signals and the evolution of plasma carotenoid levels in birds.

Sexual selection has resulted in a wide array of ornaments used in mate choice, and such indicator traits signal quality honestly when they bear costs, precluding cheating. Carotenoid-dependent coloration has attracted considerable attention in this context, because investing carotenoids in coloration has to be traded off against its physiological functions; carotenoids are antioxidants and increase immunocompetence. This trade-off is hypothesized to underlie the honesty of carotenoid-dependent coloration, signaling the "handicap" of allocating carotenoids away from somatic maintenance toward sexual display. Utilizing recent advances in modeling adaptive evolution, we used a comparative approach to investigate the evolution of plasma carotenoid levels using a species-level phylogeny of 178 bird species. We find that the evolutionary optimum for carotenoid levels is higher in lineages that evolved carotenoid-dependent coloration, with strong attraction toward this optimum. Hence, carotenoids do not appear to be limiting, given that higher carotenoid levels readily evolve in response to the evolution of carotenoid-dependent coloration. These findings challenge the assumption that carotenoids are a scarce resource and thus also challenge the hypothesis that physiological resource value of carotenoids underlies honesty of carotenoid-dependent traits. Therefore, the comparative evidence suggests that other factors, such as the acquisition and incorporation of carotenoids, are involved in maintaining signal honesty.