Analyzing RNA for diagnosing infection type
Inventors
Eden, Eran • Oved, Kfir • COHEN-DOTAN, Assaf • NAVON, Roy • BOICO, Olga • KRONENFELD, Gali • SIMON, Einav
Assignees
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Publication Number
US-12338497-B2
Publication Date
2025-06-24
Expiration Date
Abstract
A method of selecting an exon of an RNA whose expression level is informative with respect to infection type of a subject is disclosed. The method comprises comparing the expression level of the RNA in a sample derived from a bacterially-infected subject and a sample derived from a virally-infected subject at a plurality of exons, wherein the exon that provides a differential expression between the bacterially-infected subject and the virally-infected subject above a predetermined level is selected as the exon of the RNA whose expression is informative with respect to infection type.
Core Innovation
The invention provides host RNA-based diagnostics that differentiate bacterial versus viral infection types by selecting informative exons and RNA determinants. It compares exon-level expression in bacterially infected and virally infected subjects to identify exon(s) that provide differential expression. The diagnostic selection is constrained by a predetermined accuracy level, using a reference value or rule in/rule out approach.
The approach measures selected exon(s) or RNA determinant(s) in a subject sample, where the sample includes RNA or cDNA formats and sample types such as whole blood or leukocyte fractions, and serum or plasma. Specific exons of RNA determinants are described as more discriminative than full-length transcripts, and the invention supports infection-type determination including mixed infections, with optional pathogen-specific RNA determinants.
The invention uses a selection strategy focused on informative exons derived from RNA determinants, including defining RNA determinants and selecting discriminative exon numbers or coordinates. It includes expression-measurement formats such as oligonucleotide probes, primer pairs, arrays/microarrays, and RNA sequencing, and it describes statistical classification algorithms to combine multiple exon/RNA determinants to improve diagnostic performance.
Claims Coverage
The independent claim covers a kit with two specifically defined RNA-targeting oligonucleotides and a limit on the number of non-identical RNAs hybridized.
Constrained oligonucleotide kit targeting human IFI27 and JUP genomic position ranges
A kit comprising at least two oligonucleotides, wherein a first oligonucleotide specifically hybridizes to human IFI27 RNA expressed from a IFI27 genomic position on the +strand of chromosome 14 selected from one of start location 94581198 to stop location 94581225, start location 94582782 to stop location 94582840, and start location 94582887 to stop location 94582955, and a second oligonucleotide specifically hybridizes to human JUP RNA expressed from a JUP genomic position on the -strand of chromosome 17 selected from one of start location 39912431 to stop location 39912456, start location 39913673 to stop location 39913745, start location 39913996 to stop location 39914036, start location 39914665 to stop location 39914742, start location 39919268 to stop location 39919310, start location 39925344 to stop location 39925443, and start location 39925740 to stop location 39925925.
Detectable moiety or array solid support and limited RNA-target breadth
The at least two oligonucleotides are attached to a detectable moiety or are attached to a solid support of an array, wherein the kit comprises oligonucleotides that hybridize to no more than 40 non-identical RNAs.
Overall, the claim coverage is directed to an oligonucleotide diagnostic kit with specified IFI27 and JUP target genomic position ranges, with oligonucleotides attached to a detectable moiety and/or an array solid support, and with a limitation that the oligonucleotides hybridize to no more than 40 non-identical RNAs.
Stated Advantages
Enables discrimination between bacterial infection and viral infection using RNA determinants and predetermined threshold levels.
Uses exon-level biomarker selection based on differential exon expression for stronger discrimination than full-length genes.
Supports kit/array formats with limited numbers of detectable RNAs/exons for assay implementation.
Identifies additional exon determinants with improved differential expression for distinguishing bacterial versus viral infections.
Provides per-exon classifier performance metrics including AUC, sensitivity, specificity, and t-test P-values.
Improved diagnostic performance using statistical classification algorithms that combine multiple exon/RNA determinants, including sensitivity, specificity, and ROC/AUC.
Documented Applications
Diagnosing infection type, including ruling in or ruling out bacterial infection versus viral infection, using RNA determinants and reference values from control samples, longitudinal studies, or confirmed-infection and improvement cohorts.
Distinguishing bacterial versus viral infections using whole-transcriptome profiling and exon-level analysis of RNA determinants from venous blood samples.
Host RNA-based diagnostics for determining infection type (bacterial versus viral), including mixed infections, using selected informative exons/RNA determinants and a rule in/rule out reference approach.
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