SUPREME: multiomics data integration using graph convolutional networks.

To pave the road towards precision medicine in cancer, patients with similar biology ought to be grouped into same cancer subtypes. Utilizing high-dimensional multiomics datasets, integrative approaches have been developed to uncover cancer subtypes. Recently, Graph Neural Networks have been discovered to learn node embeddings utilizing node features and associations on graph-structured data. Some integrative prediction tools have been developed leveraging these advances on multiple networks with some limitations. Addressing these limitations, we developed SUPREME, a node classification framework, which integrates multiple data modalities on graph-structured data. On breast cancer subtyping, unlike existing tools, SUPREME generates patient embeddings from multiple similarity networks utilizing multiomics features and integrates them with raw features to capture complementary signals. On breast cancer subtype prediction tasks from three datasets, SUPREME outperformed other tools. SUPREME-inferred subtypes had significant survival differences, mostly having more significance than ground truth, and outperformed nine other approaches. These results suggest that with proper multiomics data utilization, SUPREME could demystify undiscovered characteristics in cancer subtypes that cause significant survival differences and could improve ground truth label, which depends mainly on one datatype. In addition, to show model-agnostic property of SUPREME, we applied it to two additional datasets and had a clear outperformance.

Do In-Hospital Rothman Index Scores Predict Postdischarge Adverse Events and Discharge Location After Total Knee Arthroplasty?

BACKGROUND: There have been efforts to reduce adverse events and unplanned readmissions after total joint arthroplasty. The Rothman Index (RI) is a real-time, composite measure of medical acuity for hospitalized patients. We aimed to examine the association among in-hospital RI scores and complications, readmissions, and discharge location after total knee arthroplasty (TKA). We hypothesized that RI scores could be used to predict the outcomes of interest. METHODS: This is a retrospective study of an institutional database of elective, primary TKA from July 2018 until December 2019. Complications and readmissions were defined per Centers for Medicare and Medicaid Services. Analysis included multivariate regression, computation of the area under the curve (AUC), and the Youden Index to set RI thresholds. RESULTS: The study cohort's (n = 957) complications (2.4%), readmissions (3.6%), and nonhome discharge (13.7%) were reported. All RI metrics (minimum, maximum, last, mean, range, 25th%, and 75th%) were significantly associated with increased odds of readmission and home discharge (all P < .05). RI scores were not significantly associated with complications. The optimal RI thresholds for increased risk of readmission were last ≤ 71 (AUC = 0.65), mean ≤ 67 (AUC = 0.66), or maximum ≤ 80 (AUC = 0.63). The optimal RI thresholds for increased risk of home discharge were minimum ≥ 53 (AUC = 0.65), mean ≥ 69 (AUC = 0.65), or maximum ≥ 81 (AUC = 0.60). CONCLUSION: RI values may be used to predict readmission or home discharge after TKA.

The Impact of Pre-Operative Healthcare Utilization on Complications, Readmissions, and Post-Operative Healthcare Utilization Following Total Joint Arthroplasty.

BACKGROUND: Identifying risk factors for adverse outcomes and increased costs following total joint arthroplasty (TJA) is needed to ensure quality. The interaction between pre-operative healthcare utilization (pre-HU) and outcomes following TJA has not been fully characterized. METHODS: This is a retrospective cohort study of patients undergoing elective, primary total hip arthroplasty (THA, N = 1785) or total knee arthroplasty (TKA, N = 2159) between 2015 and 2019 at a single institution. Pre-HU and post-operative healthcare utilization (post-HU) included non-elective healthcare utilization in the 90 days prior to and following TJA, respectively (emergency department, urgent care, observation admission, inpatient admission). Multivariate regression models including age, gender, American Society of Anesthesiologists, Medicaid status, and body mass index were fit for 30-day readmission, Centers for Medicare and Medicaid services (CMS)-defined complications, length of stay, and post-HU. RESULTS: The 30-day readmission rate was 3.2% and 3.4% and the CMS-defined complication rate was 3.8% and 2.9% for THA and TKA, respectively. Multivariate regression showed that for THA, presence of any pre-HU was associated with increased risk of 30-day readmission (odds ratio [OR] 2.85, 95% confidence interval [CI] 1.48-5.50, P = .002), CMS complications (OR 2.42, 95% CI 1.27-4.59, P = .007), and post-HU (OR 3.65, 95% CI 2.54-5.26, P < .001). For TKA, ≥2 pre-HU events were associated with increased risk of 30-day readmission (OR 3.52, 95% CI 1.17-10.61, P = .026) and post-HU (OR 2.64, 95% CI 1.29-5.40, P = .008). There were positive correlations for THA (any pre-HU) and TKA (≥2 pre-HU) with length of stay and number of post-HU events. CONCLUSION: Patients who utilize non-elective healthcare in the 90 days prior to TJA are at increased risk of readmission, complications, and unplanned post-HU. LEVEL OF EVIDENCE: Level III.

Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.

To understand driving biological factors for complex diseases like cancer, regulatory circuity of genes needs to be discovered. Recently, a new gene regulation mechanism called competing endogenous RNA (ceRNA) interactions has been discovered. Certain genes targeted by common microRNAs (miRNAs) "compete" for these miRNAs, thereby regulate each other by making others free from miRNA regulation. Several computational tools have been published to infer ceRNA networks. In most existing tools, however, expression abundance sufficiency, collective regulation, and groupwise effect of ceRNAs are not considered. In this study, we developed a computational tool named Crinet to infer genome-wide ceRNA networks addressing critical drawbacks. Crinet considers all mRNAs, lncRNAs, and pseudogenes as potential ceRNAs and incorporates a network deconvolution method to exclude the spurious ceRNA pairs. We tested Crinet on breast cancer data in TCGA. Crinet inferred reproducible ceRNA interactions and groups, which were significantly enriched in the cancer-related genes and processes. We validated the selected miRNA-target interactions with the protein expression-based benchmarks and also evaluated the inferred ceRNA interactions predicting gene expression change in knockdown assays. The hub genes in the inferred ceRNA network included known suppressor/oncogene lncRNAs in breast cancer showing the importance of non-coding RNA's inclusion for ceRNA inference. Crinet-inferred ceRNA groups that were consistently involved in the immune system related processes could be important assets in the light of the studies confirming the relation between immunotherapy and cancer. The source code of Crinet is in R and available at https://github.com/bozdaglab/crinet.