US 12,168,800 B2
Methods and systems for evaluating microsatellite instability status
Sameh El-Difrawy, Santa Clarita, CA (US)
Assigned to Life Technologies Corporation, Carlsbad, CA (US)
Filed by LIFE TECHNOLOGIES CORPORATION, Carlsbad, CA (US)
Filed on Dec. 5, 2023, as Appl. No. 18/529,188.
Application 18/529,188 is a continuation of application No. 18/152,813, filed on Jan. 11, 2023, granted, now 11,866,778.
Application 18/152,813 is a continuation of application No. 16/595,681, filed on Oct. 8, 2019, granted, now 11,572,586, issued on Feb. 7, 2023.
Claims priority of provisional application 62/858,387, filed on Jun. 7, 2019.
Claims priority of provisional application 62/785,596, filed on Dec. 27, 2018.
Claims priority of provisional application 62/745,161, filed on Oct. 12, 2018.
Prior Publication US 2024/0175084 A1, May 30, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. G16B 40/20 (2019.01); C12Q 1/6809 (2018.01); C12Q 1/6869 (2018.01); C12Q 1/6886 (2018.01); G16B 20/00 (2019.01); G16B 50/00 (2019.01)
CPC C12Q 1/6869 (2013.01) [C12Q 1/6809 (2013.01); C12Q 1/6886 (2013.01); G16B 20/00 (2019.02); G16B 40/20 (2019.02); G16B 50/00 (2019.02); C12Q 2600/156 (2013.01)] 20 Claims
OG exemplary drawing
 
1. A computer-readable media comprising machine-readable instructions that, when loaded in a machine-readable memory and executed by a processor, are configured to cause a system to perform a method for detecting microsatellite instability (MSI) in a sample, said method comprising:
receiving a plurality of nucleic acid sequence reads corresponding to a plurality of marker regions for MSI, wherein each of the sequence reads includes a left flank sequence, right flank sequence and a repeat region of bases positioned between a rightmost base of the left flank sequence and a leftmost base of the right flank sequence, wherein the repeat region includes a number of repeats of a repeated sequence of bases corresponding to a particular marker region of the plurality of marker regions;
for each sequence read corresponding to the plurality of marker regions for MSI, aligning at least a portion the left flank sequence with a reference left flank, wherein the reference left flank borders a reference repeat region of a reference nucleic acid sequence corresponding to the particular marker region;
for the repeat region corresponding to a target homopolymer in the sequence reads, calculating a histogram of homopolymer signal values based on signal measurements for the target homopolymer, wherein at least a portion of the marker regions corresponds to target homopolymers;
determining a score per marker by calculating a weighted sum of features of the histogram of homopolymer signal values for each marker region corresponding to the target homopolymers to produce a plurality of scores;
applying a threshold score to the score per marker; and
combining the plurality of scores to form a total MSI score for the sample.