Approaches that integrate molecular network information and tumor genome data could complement gene-based statistical tests to identify likely new cancer genes, but are challenging to validate at scale and their predictive value remains unclear. We developed a robust statistic (NetSig) that integrates protein interaction networks and data from 4,742 tumor exomes and used it to accurately classify known driver genes in 60% of tested tumor types and to predict 62 new candidates. We designed a quantitative experimental framework to compare the in vivo tumorigenic potential of NetSig candidates, known oncogenes and random genes in mice showing that NetSig candidates induce tumors at rates comparable to known oncogenes and 10-fold higher than random genes. By reanalyzing nine tumor-inducing NetSig candidates in 242 patients with oncogene-negative lung adenocarcinomas, we find that two (AKT2 and TFDP2) are significantly amplified. Overall, we illustrate a scalable integrated computational and experimental workflow to expand discovery from cancer genomes.

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Background: Postprandial hyperglycemia (PPH) and circadian glucose concentration fluctuations recorded in the home environment of dogs with naturally occurring diabetes mellitus (DM) have not been reported. Objectives: To determine if a flash glucose monitoring system (FGMS; FreeStyle Libre) can detect PPH and circadian fluctuations in glucose concentrations in dogs with variably controlled DM. Animals: Fourteen client-owned dogs with DM. Methods: Prospective observational study. Interstitial glucose (IG) concentrations measured by the FGMS during a 13-day study period were analyzed. Results: A total of 17, 446 FGMS IG concentrations were analyzed. For all dogs analyzed together, median IG concentration measured within 30 (288 mg/dL), 60 (286 mg/dL), 90 (285 mg/dL), and 120 (285 mg/dL) minutes of meals was each significantly higher than the median IG concentration at all other times (260 mg/dL, 259 mg/dL, 258 mg/dL, and 257 mg/dL, respectively; range, 40-500 mg/dL; P < .001 for each). Median night-time IG concentration measured from all dogs on 3,547 samples recorded between 1:00 am and 6:00 am (268 mg/dL; range, 40-500 mg/dL) was significantly higher than median IG measured on 13, 899 samples at all other time points (259 mg/dL; range, 40-500 mg/dL; P < .001). Conclusions and Clinical Importance: The FGMS can be used for future studies of PPH and circadian fluctuations of glucose concentrations in dogs with DM in their home environment.

Here, we developed an in situ RNA detection assay for RNA generated by the SARS-CoV-2 virus. We found viral RNA in lung, lymph node, and placenta samples from pathology specimens from COVID patients. Using high-magnification microscopy, we can visualize the subcellular distribution of these RNA in single cells.