US 12,154,664 B2
Systems and methods for determining microsatellite instability
Shile Zhang, San Diego, CA (US); Alex S. So, San Diego, CA (US); Shannon Kaplan, San Diego, CA (US); Kristina M. Kruglyak, San Diego, CA (US); and Sven Bilke, San Diego, CA (US)
Assigned to Illumina, Inc., San Diego, CA (US)
Filed by ILLUMINA, INC., San Diego, CA (US)
Filed on Nov. 14, 2018, as Appl. No. 16/191,142.
Claims priority of provisional application 62/652,151, filed on Apr. 3, 2018.
Claims priority of provisional application 62/587,350, filed on Nov. 16, 2017.
Prior Publication US 2019/0156922 A1, May 23, 2019
Int. Cl. G16H 10/60 (2018.01); C12Q 1/6869 (2018.01); C12Q 1/6886 (2018.01); G01N 33/50 (2006.01); G06F 9/30 (2018.01); G16B 20/20 (2019.01); G16B 30/20 (2019.01)
CPC G16H 10/60 (2018.01) [C12Q 1/6886 (2013.01); G01N 33/50 (2013.01); G06F 9/3004 (2013.01); G16B 20/20 (2019.02); G16B 30/20 (2019.02); C12Q 1/6869 (2013.01)] 14 Claims
 
1. A computer-implemented method, comprising:
acquiring, using a microprocessor, genomic reference sequence data from a plurality of reference biological samples corresponding to respective individuals;
analyzing the reference sequence data to generate a distribution of sequences at each of a plurality of microsatellite regions;
determining ethnic group variability of the distribution at each of the plurality of microsatellite regions for the plurality of reference biological samples, the ethnic group variability including genomic sequence differences;
identifying ethnically biased microsatellite regions of the plurality of microsatellite regions based on the ethnic group variability at each of the plurality of microsatellite regions;
generating a reference sample dataset by removing or filtering the ethnically biased microsatellite regions from the reference sequence data of the plurality of reference biological samples, wherein reference sequence data is assessed based on having a depth of sequencing of at least 20 reads prior to inclusion in the hypothetical reference sample sequence;
assessing microsatellite instability based on a comparison of sequence data from a sample of interest to the hypothetical reference sample sequence, wherein the sample of interest is derived from a tumor sample of an individual and wherein a matched normal sample from the individual to the sample of interest is not available; and
determining that microsatellite instability for the sample of interest is classified as microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) and, based on such a classification, causing an immune checkpoint inhibitor to be administered to the individual.