Host-Viral Transcriptomic Classifier for COVID-19 Diagnosis
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Solution Overview
Problem
Current COVID-19 diagnostic methods, such as PCR and antigen tests, face challenges with sensitivity and are prone to false positives due to environmental contamination or cross-reactivity, necessitating an improved approach for accurate testing and prognosis.
Innovation Solution
Development and validation of a 2-gene host-viral transcriptomic classifier that measures the expression levels of specific human genes (IFI6, IFI27, GSTA2, GBP5, etc.) in conjunction with SARS-CoV-2 viral RNA to differentiate between infected and non-infected individuals, and distinguish COVID-19 from other acute respiratory illnesses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PCR and antigen tests are used for COVID-19 diagnosis, then viral detection is achieved, but false positives occur due to environmental contamination or cross-reactivity
Solution Approach 1:
The patent segments the diagnostic approach into two independent components: (1) host gene expression profiling measuring multiple human genes simultaneously, and (2) viral RNA detection. By analyzing host transcriptional responses rather than relying solely on viral markers, the method reduces false positives from environmental contamination or cross-reactivity that affect traditional PCR tests.
Solution Approach 2:
The patent introduces host gene expression profiles as an intermediary indicator. Instead of directly detecting viral RNA which is susceptible to contamination, the method measures the host's transcriptional response to infection. This intermediary approach provides indirect evidence of viral presence while being less prone to false positives from environmental factors.
2Reliability
If traditional diagnostic methods are used, then testing can be performed, but sensitivity is limited leading to false negative results
Solution Approach 1:
The patent merges multiple gene expression measurements into a composite diagnostic signature. By simultaneously measuring the expression levels of multiple host genes (e.g., IFI6, GBP5, CCL3, GSTA2) and analyzing their combined pattern, the method achieves higher sensitivity than individual gene markers or traditional single-target PCR assays.
Solution Approach 2:
The patent changes the diagnostic parameter from direct viral RNA quantification to host gene expression profiling. This parameter transformation allows detection of viral infection through the host's biological response, which may be detectable even when viral loads are below the detection threshold of conventional PCR methods.
3Reliability
If comprehensive viral and host gene analysis is performed, then diagnostic accuracy is improved, but assay complexity increases
Solution Approach 1:
The patent extracts a simplified diagnostic signature from comprehensive transcriptomic data. By identifying and focusing on a specific subset of host genes that show characteristic expression patterns during SARS-CoV-2 infection, the method reduces the complexity of full transcriptome analysis while maintaining high diagnostic accuracy.
Data Source
AI summary
Provided herein are lists of combined host-viral gene markers that can be used for identifying COVID-19 in a subject and/or determining severity of disease. The host-viral diagnostic methods, compositions and systems disclosed herein are used to classify human subjects pre-diagnosis, with or without symptoms of COVID-19, based on the expression levels of the identified gene markers.