Patent SG-11201807576Q-A (SG)
Title: High throughput method for accurate prediction of compound-induced liver injury
Inventor: ZINK DANIELE
IPC: G01N33/533
Filed: 2017-04-11
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 19 October 2017 (19.10.2017) WIPO I PCT (10) International Publication Number WO 2017/180061 Al 1111111111111101110101011111010111110 0111111011111110111111011111111111110111111 Figure 2 Dose response curve and estimation Image segmentation and feature extraction W O 20 17 / 18006 1 Al (51) International Patent Classification: C12Q 1/68 (2006.01) G06T 7/00 (2017.01) GO1N 33/533 (2006.01) GOOF 19/00 (2011.01) GO1N 33/68 (2006.01) (21) International Application Number: PCT/SG2017/050206 (22) International Filing Date: 11 April 2017 (11.04.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 10201602855P 11 April 2016 (11.04.2016) SG (71) Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH [SG/SG]; 1 Fusionopolis Way, #20-10 Connexis North Tower, Singapore 138632 (SG). (72) Inventors: ZINK, Daniele; c/o Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, #09-01, The Nanos, Singapore 138669 (SG). AKBAR HUSSAIN, Nur Faezah Begum; c/o Institute of Bioengineering and Nano- technology, 31 Biopolis Way, #09-01, The Nanos, Singa- pore 138669 (SG). LOO, Lit Hsin; c/o Bioinformatics In- stitute, 30 Biopolis Street, #07-01 Matrix, Singapore 138671 (SG). LAM, Ah Wah; c/o Bioinformatics Insti- tute, 30 Biopolis Street, #07-01 Matrix, Singapore 138671 (SG). (74) Agent: SPRUSON & FERGUSON (ASIA) PTE LTD; P.O. Box 1531, Robinson Road Post Office, Singapore 903031 (SG). (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, 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, [Continued on next page] — (54) Title: HIGH THROUGHPUT METHOD FOR ACCURATE PREDICTION OF COMPOUND-INDUCED LIVER INJURY (57) : A method and system for predicting liver injury in vivo due to hepatocyte damage by a test compound are provided. The method includes ac- quiring images of fluorescently stained cells obtained from a cell culture in Images which the cells have been treated with a dose-range of at least the test com- pound and its vehicle. The cells may be hepatic cells including primary or im- mortalized hepatocytes, hepatoma cells or induced pluripotent stem cell-derived Background correction hepatocyte-like cells. The acquired images are segmented. The method further includes extracting and analyzing one or more phenotypic features from the seg- mented images, wherein the one or more phenotypic features are selected from Al g orithm S1 the group of intensity, textural, morphological, or ratiometric features consisting Algorithm S2 of (a) features of DNA, (b) features of RELA (NF-KB p65), and (c) features of actin filaments at different subcellular regions and d) features of cellular organ- elles and their substructures in the segmented images. Finally, the method in- cludes normalizing results from the treated samples to vehicle controls and pre- RectgsW41Witife\",: .elimination pound-induced normalized changes of the extracted and selected phenotypic dicting the probability of liver injury by the test compound based on test com- features using machine learning methods. WO 2017/180061 Al MIDEDIMOMOIDEIHMEMOMOHMONIMMOVOIMIE TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, Declarations under Rule 4.17: VN, ZA, ZM, ZW. of inventorship (Rule 4.17(iv)) (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). 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))