Methods and devices for nucleic acid-based real-time determination of disease states
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Publication Number
US-11749378-B2
Publication Date
2023-09-05
Expiration Date
Abstract
The present invention is directed to methods and devices for real-time diagnosis of disease states in subjects, for example, infections caused by one or more microorganisms or cancer.
Core Innovation
The invention concerns treating a disease or infection caused by a microorganism in a subject by administering a compound that inhibits the growth of the microorganism when a calculated significance score meets or exceeds a threshold value. The significance score is computed as a probability of finding a compared sequence read mapping to a particular microorganism in the subject, based on the number of sequence reads mapping to the particular microorganism and the number of sequence reads mapping to a species over time.
To calculate the significance score, the method compares sequence reads obtained by sequencing nucleic acids present in a biological sample from the subject with one or more databases containing genetic information from a control subject of the same species and genetic information from a plurality of microorganisms. Mapping is determined for whether a compared sequence read maps to a species comprised within the one or more databases, and sequence reads mapping to a species comprise sequence reads mapping to the species of the subject.
The method is further tied to clinical interpretation of the calculated significance score, including determining that the microorganism is present and/or relevant for causing the disease when the significance score meets or exceeds the threshold value. Embodiments described include monitoring infection and cancer, including cancer relapse or recurrence, with the ability to compute significance over time and enable early termination when relevance crosses a threshold.
Claims Coverage
The partial content includes three independent claims. Across these claims, the inventive structure combines sequencing nucleic acids from a biological sample, comparing sequence reads against databases containing genetic information from a control subject of the same species and genetic information from multiple microorganisms, computing an over-time significance score from read mapping counts, and administering a compound that inhibits growth when the significance score meets or exceeds a threshold.
Treatment based on thresholded microorganism significance score
Administering to the subject a compound that inhibits the growth of a microorganism whose significance score meets or exceeds a threshold value.
Database comparison using control subject of same species and plurality of microorganisms
Comparing sequence reads with one or more databases comprising the genetic information from a control subject of the same species and the genetic information from a plurality of microorganisms to determine whether or not a compared sequence read maps to a species comprised within the one or more databases.
Over-time computation from read mapping counts to microorganism versus species
Determining over time the number of compared sequence reads mapping to a particular microorganism and the number of compared sequence reads mapping to a species, wherein the sequence reads mapping to a species comprise sequence reads mapping to the species of the subject, and computing a significance score for the probability of finding in the subject a compared sequence read mapping to the particular microorganism based on the number of compared sequence reads mapping to the particular microorganism and the number of compared sequence reads mapping to a species.
Sequencing nucleic acids from biological sample to generate sequence reads
Sequencing nucleic acids present in a biological sample obtained from the subject to generate the sequence reads that are then compared to the one or more databases.
Species mapping includes reads mapping to the subject’s species
The sequence reads mapping to a species comprise sequence reads mapping to the species of the subject.
Across the independent claims, the inventive concept is the same: compute an over-time significance score from read mapping counts of a particular microorganism versus a species using databases that include genetic information from a control subject of the same species and from multiple microorganisms, and treat by administering a compound that inhibits growth when the significance score meets or exceeds a threshold.
Stated Advantages
Discriminating pathogens from commensals or contamination.
Enabling treatment selection.
Documented Applications
Monitoring infection and cancer, including cancer relapse or recurrence.
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