WO2023017402 - METHODS FOR IDENTIFYING MICROSATELLITE INSTABILITY HIGH (MSI-H) IN DNA SAMPLES

National phase entry:
Publication Number WO/2023/017402
Publication Date 16.02.2023
International Application No. PCT/IB2022/057382
International Filing Date 08.08.2022
Title **
[English] METHODS FOR IDENTIFYING MICROSATELLITE INSTABILITY HIGH (MSI-H) IN DNA SAMPLES
[French] PROCÉDÉS D'IDENTIFICATION DE FORTE INSTABILITÉ DES MICROSATELLITES (MSI-H) DANS DES ÉCHANTILLONS D'ADN
Applicants **
CANEXIA HEALTH INC. Suite #204 Donald Rix Building, 2389 Health Sciences Mall Vancouver, British Columbia V6T 1Z3, CA
Inventors
PERERA, Dilmi Chathurika Apt 309, 5555 Dunbar Street Vancouver, British Columbia V6N 1W5, CA
Priority Data
63/231,098   09.08.2021   US
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Abstract[English] A method is proposed where the distribution of repeats relative to the negative control sample in each run are calculated for each MSI loci. This distribution along with the average, are used as features to train a random forest classifier to identify MSI-H samples from other samples which are either MSS or MSI-L samples, collectively referred to as MS-Stable. In particular, the method distinguishes samples subject to artificial replication errors, such as PCR errors and sequencing errors. The resulting output that is produced is the probability of the sample being MSI-H, which is the MSI score of the sample. When samples are classified as MSI-H, the finding is reported as indicative of sensitivity to immune modulation-checkpoint inhibitor treatment.[French] L'invention concerne un procédé dans lequel la distribution de répétitions par rapport à l'échantillon de témoin négatif dans chaque plage est calculée pour chaque locus MSI. Ladite distribution, ainsi que la moyenne, sont utilisées en tant que caractéristiques afin d'entraîner un classificateur de forêt aléatoire pour identifier des échantillons MSI-H à partir d'autres échantillons qui sont soit des échantillons MSS soit des échantillons MSI-L, désignés collectivement comme MS-Stable. En particulier, le procédé distingue des échantillons soumis à des erreurs de réplication artificielle, telles que des erreurs de PCR et des erreurs de séquençage. La sortie résultante produite est la probabilité que l'échantillon soit MSI-H, qui est le score MSI de l'échantillon. Lorsque des échantillons sont classés comme MSI-H, la découverte est rapportée comme étant indicative de la sensibilité au traitement inhibiteur du point de contrôle de la modulation immunitaire.
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