Interactive web-based identification and visualization of transcript shared sequences.

We have developed TraC (Transcript Consensus), a web-based tool for detecting and visualizing shared sequences among two or more mRNA transcripts such as splice variants. Results including exon-exon boundaries are returned in a highly intuitive, data-rich, interactive plot that permits users to explore the similarities and differences of multiple transcript sequences. The online tool (http://labs.pathology.jhu.edu/nauen/trac/) is free to use. The source code is freely available for download (https://github.com/nauenlab/TraC).

Using Shapes of COVID-19 Positive Patient-Specific Trajectories for Mortality Prediction.

Machine learning can be used to identify relevant trajectory shape features for improved predictive risk modeling, which can help inform decisions for individualized patient management in intensive care during COVID-19 outbreaks. We present explainable random forests to dynamically predict next day mortality risk in COVID -19 positive and negative patients admitted to the Mount Sinai Health System between March 1st and June 8th, 2020 using patient time-series data of vitals, blood and other laboratory measurements from the previous 7 days. Three different models were assessed by using time series with: 1) most recent patient measurements, 2) summary statistics of trajectories (min/max/median/first/last/count), and 3) coefficients of fitted cubic splines to trajectories. AUROC and AUPRC with cross-validation were used to compare models. We found that the second and third models performed statistically significantly better than the first model. Model interpretations are provided at patient-specific level to inform resource allocation and patient care.

BEHRTDAY: Dynamic Mortality Risk Prediction using Time-Variant COVID-19 Patient Specific Trajectories.

Incorporating repeated measurements of vitals and laboratory measurements can improve mortality risk-prediction and identify key risk factors in individualized treatment of COVID-19 hospitalized patients. In this observational study, demographic and laboratory data of all admitted patients to 5 hospitals of Mount Sinai Health System, New York, with COVID-19 positive tests between March 1st and June 8th, 2020, were extracted from electronic medical records and compared between survivors and non-survivors. Next day mortality risk of patients was assessed using a transformer-based model BEHRTDAY fitted to patient time series data of vital signs, blood and other laboratory measurements given the entire patients' hospital stay. The study population includes 3699 COVID-19 positive (57% male, median age: 67) patients. This model had a very high average precision score (0.96) and area under receiver operator curve (0.92) for next-day mortality prediction given entire patients' trajectories, and through masking, it learnt each variable's context.

An interactive web-based application for Comprehensive Analysis of RNAi-screen Data.

RNAi screens are widely used in functional genomics. Although the screen data can be susceptible to a number of experimental biases, many of these can be corrected by computational analysis. For this purpose, here we have developed a web-based platform for integrated analysis and visualization of RNAi screen data named CARD (for Comprehensive Analysis of RNAi Data; available at https://card.niaid.nih.gov). CARD allows the user to seamlessly carry out sequential steps in a rigorous data analysis workflow, including normalization, off-target analysis, integration of gene expression data, optimal thresholds for hit selection and network/pathway analysis. To evaluate the utility of CARD, we describe analysis of three genome-scale siRNA screens and demonstrate: (i) a significant increase both in selection of subsequently validated hits and in rejection of false positives, (ii) an increased overlap of hits from independent screens of the same biology and (iii) insight to microRNA (miRNA) activity based on siRNA seed enrichment.