Patent SG-11201806812S-A (SG)
Title: Methods and systems for detection of abnormal karyotypes
Inventor: MAXWELL EVAN
IPC: G16B50/00
Filed: 2017-02-13
Abstract: WO 17 / 13980 1 Al 100 FIG 1 116 . / -102 ,-104 -108 110 Z-SCORE NORMALIZE THE RESIDUALS DETECT DEVIATION OF THE READ COVERAGE PROFILES FROM THE EXPECTED READ COVERAGE PRCHILFS DEFINED BY THE RESIDUAL APPLY LINEAR REGRESSION MODEL TO COMPUTE EXPECTED READ COVERAGE PROFILES NORMALIZE READ COVERAGE PROFILES COMPUTE A READ COVERAGE PROFILE FOR INDIVIDUAL SAMPLES RELATIVE TO EACH CHROMOSOME DETERMINE GC-CONTENT AND WPPABIUTY METRICS FOR EXONIC REGIONS DETERMINE A p-VALUE BASED ON THE Z- SCORE FOR EACH CHROMOSOME TO IDENTIFY SIGNIFICANTLY LARGE RESIDUALS, REPRESENTING ABNORMAL KARYOTYPES -114 DETECT AND EXCLUDE OUTLIERS BY FLAGGING SAMPLES WITH EXTREME LEVERAGE (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/139801 Al 17 August 2017 (17.08.2017) WIPO I PCT 111111111111110111011111111111010111110 011101111111111011111011111111111110111111 (51) International Patent Classification: G06F 19/18 (2011.01) (21) International Application Number: PCT/US2017/017734 (22) International Filing Date: 13 February 2017 (13.02.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/294,669 12 February 2016 (12.02.2016) US (71) Applicant: REGENERON PHARMACEUTICALS, INC. [US/US]; 777 Old Saw Mill River Road, Tarrytown, NY 10591 (US). (72) Inventors: MAXWELL, Evan; c/o Regeneron Pharma- ceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591 (US). HABEGGER, Lukas; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591 (US). REID, Jeffrey; c/o Regener- on Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591 (US). (74) Agents: BROWN, Charley, F. et al.; Ballard Spahr, LLP, 999 Peachtree Street, Suite 1000, Atlanta, GA 30309 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, [Continued on next page] (54) Title: METHODS AND SYSTEMS FOR DETECTION OF ABNORMAL KARYOTYPES (57) : Methods and systems for detecting abnormal karyotypes are disclosed. An example method can comprise determining read cover- age data, allele balance distributions of heterozygous SNPs, and chromo- somal segments where heterozygosity is not observed. The methods and systems can then determine one or more metrics which can be indicative of abnormal karyotype(s). WO 2017/139801 Al MIDEDIMOMOIDEIR010130111001HEIIMMOVOIMIE KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(ii)) Published: with international search report (Art. 21(3)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h))