Patent SG-11201906428S-A (SG)
Title: Methods and systems for generation and error-correction of unique molecular index sets with heterogeneous molecular lengths
Inventor: WU KEVIN
IPC: G16B25/20
Filed: 2018-01-05
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 26 July 2018 (26.07.2018) WIP0 I PCT omit VIII °nolo 010 mil Imo oimIE (10) International Publication Number WO 2018/136248 Al (51) International Patent Classification: GOOF 19/22 (2011.01) GOOF 19/20 (2011.01) (21) International Application Number: PCT/US2018/012669 (22) International Filing Date: 05 January 2018 (05.01.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/447,851 18 January 2017 (18.01.2017) US (71) Applicant: ILLUMINIA, INC. [US/US]; 5200 Illumina Way, San Diego, California 92122 (US). (72) Inventors: WU, Kevin; 5200 Illumina Way, San Diego, California 92122 (US). ZHAO, Chen; 5200 Illumina Way, San Diego, California 92122 (US). CHUANG, Han-Yu; 5200 Illumina Way, San Diego, California 92122 (US). SO, Alex; 5200 Illumina Way, San Diego, California 92122 (US). TANNER, Stephen; 5200 Illumina Way, San Diego, California 92122 (US). GROSS, Stephen M.; 5200 Illumi- na Way, San Diego, California 92122 (US). (74) Agent: ZHOU, Feng et al.; WEAVER AUSTIN VIL- LENEUVE & SAMPSON LLP, P. 0. BOX 70250, OAK- LAND, California 94612-0250 (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, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, 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, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). (54) Title: METHODS AND SYSTEMS FOR GENERATION AND ERROR-CORRECTION OF UNIQUE MOLECULAR INDEX SETS WITH HETEROGENEOUS MOLECULAR LENGTHS 132 - Figure 1C Sequencing Using vNRUMIs Apply adapters to DNA fragments in the sample to obtain DNA-adapter products, wherein each adapter has a nonrandom unique molecular index, and wherein nonrandom unique molecular indexes of the adapters have at least two different molecular lengths and form a set of variable-length, non- random unique molecular indices (vNRUMIs) Amplify the DNA-adapter products to obtain a plurality of amplified polynucleotides (57) : The disclosed embodiments concern methods, apparatus, systems and computer program products for determining sequences of in- terest using unique molecular index sequences that are uniquely associa- ble with individual polynucleotide fragments, including sequences with low allele frequencies and long sequence length. In some implementation s, the unique molecular index sequences include variable-length nonran- dom sequences. In some implementations, the unique molecular index se- quences are associated with the individual polynucleotide fragments based on alignment scores indicating similarity between the unique molecular index sequences and subsequences of sequence reads obtained from the in- dividual polynucleotide fragments. System, apparatus, and computer pro- gram products are also provided for determining a sequence of interest implementing the methods disclosed. 130 131 — 133 W O 20 18/ 136 248 Al Sequence the plurality of amplified polynucleotides, thereby obtaining a plurality of reads associated with the set of vNRUMIs 134 Identify, among the plurality of reads, reads associated with a same vNRUMI 135 Determine a sequence of a DNA fragment in the sample using the reads associated with the same vNRUMI [Continued on next page] WO 2018/136248 Al MIDEDIMOHNOBEIEDEMEMEDIM1111111011111111111111111 Published: — with international search report (Art. 21(3))