Siddiqui, J. K. | Search bioRxiv

bioRxiv2020

RNA Editing Signatures Predict Response to Immunotherapies in Melanoma Patients

Summary ParagraphImmunotherapy has improved the prognosis for half of the melanoma patients, prompting a need to understand differences between responding and non-responding patients. Gene expression profiling of tumors has focused on deriving primarily immune-related signatures, however these have shown limited predictive power. Recent studies have highlighted the role of RNA editing in modulating resistance to immunotherapy. This has led us to test whether RNA editing activity can be predictive of response in publicly available datasets of immunotherapy-treated melanoma patients. Here, we identified RNA editing signatures that were able to predict with very high accuracy and confidence patient responses and outcomes. Our analysis, however, demonstrates that RNA editing by itself is sufficient as a strong predictive tool for examining sensitivity of melanoma patients to immunotherapy.

bioinformatics↗

bioRxiv2020

REMBRANDT: A high-throughput barcoded sequencing approach for COVID-19 screening.

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV), is a highly infectious RNA virus. A still-debated percentage of patients develop coronavirus disease 2019 (COVID-19) after infection, whose symptoms include fever, cough, shortness of breath and fatigue. Acute and life-threatening respiratory symptoms are experienced by 10-20% of symptomatic patients, particularly those with underlying medical conditions that includes diabetes, COPD and pregnancy. One of the main challenges in the containment of COVID-19 is the identification and isolation of asymptomatic/pre-symptomatic individuals. As communities re-open, large numbers of people will need to be tested and contact-tracing of positive patients will be required to prevent additional waves of infections and enable the continuous monitoring of the viral loads COVID-19 positive patients. A number of molecular assays are currently in clinical use to detect SARS-CoV-2. Many of them can accurately test hundreds or even thousands of patients every day. However, there are presently no testing platforms that enable more than 10,000 tests per day. Here, we describe the foundation for the REcombinase Mediated BaRcoding and AmplificatioN Diagnostic Tool (REMBRANDT), a high-throughput Next Generation Sequencing-based approach for the simultaneous screening of over 100,000 samples per day. The REMBRANDT protocol includes direct two-barcoded amplification of SARS-CoV-2 and control amplicons using an isothermal reaction, and the downstream library preparation for Illumina sequencing and bioinformatics analysis. This protocol represents a potentially powerful approach for community screening, a major bottleneck for testing samples from a large patient population for COVID-19.

molecular biology↗