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

Abstract

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.

Figure 1.

Integration of the longitudinal clinico-genomic data from AACR GENIE BPC in cBioPortal. Multidimensional GENIE BPC datasets have been harmonized across the four participating centers. AACR Project GENIE includes molecular and basic clinical data from 19 institutions. GENIE BPC enriches this data for four institutions with additional clinical longitudinal elements. The data are publicly available in cBioPortal (https://genie.cbioportal.org). The complete clinical and genomic data can be downloaded from Synapse (https://www.synapse.org/genie).

Figure 2.

Visualization of longitudinal clinical and genomic profile of a patient in GENIE BPC. A, The timeline shows biopsies and resections, diagnoses, lines of treatments, as well as assessments from imaging and medical oncology. B, The genomic event tables show detailed information about mutations, structural variants, and copy-number alterations in each of the samples. The mutations table for instance shows the effect on the protein and the variant allele frequency. The samples column in each of the tables indicates in which sample(s) the event was found; a dash indicates that the sample was not profiled for that gene. All genomic events have an annotation column with information from other resources about that event, including, for example, OncoKB, which is indicated by a blue target icon. Hovering over those icons gives additional information in a tooltip. C, The tooltip is shown for the OncoKB annotation of ALK G1202R. It mentions that the ALK G1202R mutation identified in sample 4 is a known resistance mutation to crizotinib.

Figure 3.

Visualization and analysis of GENIE BPC dataset in cBioPortal. A, Study view. Overview of clinical and genomic data of the GENIE BPC NSCLC cohort; samples can be selected by their treatment status and then compared. B, Comparison view. Example comparison of samples collected before and/or after a patient was treated with crizotinib to identify genomic alterations potentially responsible for acquired resistance to treatment. C, Results view. OncoPrint with resistance alterations in post-crizotinib samples and a lollipop highlighting resistance mutations in the kinase domain of ALK. D, Survival analysis, showing a comparison of survival between TP53 mutant versus wild-type patients with NSCLC.