Supplementary Information

No. Description Page No. 1. Supplementary Table 1. List of TCGA samples used in analyses 2 2. Supplementary Figure S1. Identification of EMT target genes 6 3. Supplementary Table 2. List of EMT-TF targets and LPA-S1P signaling 7 components 4. Supplementary Figure S2. Tumor classification by M-classification approach 8 5. Supplementary Figure S3. Derivation of the 39 metastases-associated gene 9 set 6. Supplementary Table 3. Literature based functional assignment of the 39 10 gene set with metastases 7. Supplementary Data1. Weighted gene co-expression network analysis 11-13 (WGCNA) and module identification (W-classification) 8. Supplementary Data 2. Classification and module gene validation in additional 14-17 Ovarian Cancer datasets (VDs) 9. Supplementary Data 3. Identification of class-defining features using Gene 18-20 Set Enrichment Analysis (GSEA) 10. Supplementary Table 4: Modules and associated Genes 21-42 11. Supplementary Table 5: Class Functionalities based on Enriched Module 43 Genes 12. Supplementary Table 6. Ovarian cancer cell line datasets 44 13. Supplementary Fig. S4. Representative Wound Healing Assay Images 45 14. Supplementary Fig. S5. Graphical representation of wound healing 46 15. Supplementary Figure S6. Representative immunofluorescence image of 46 Class2 invasion 16. Supplementary Figure S7. Representative Immunofluorescence expression 47 images of markers 17. Supplementary Table 7. Correlation between TCGA subtypes and MW 47 classes 18. SupplementaryTable 8. Correlation between MW classes and iE-iM subtypes 47

1 Supplementary Table 1. List of TCGA samples used in analyses Agilent data samples Affymetrix data samples TCGA-04-1536 TCGA-10-0931 TCGA-61-2101 TCGA-24-1423 TCGA-13-0791 TCGA-09-1659 TCGA-10-0933 TCGA-61-2102 TCGA-13-1489 TCGA-13-0724 TCGA-09-1661 TCGA-10-0934 TCGA-61-2104 TCGA-13-1499 TCGA-13-0765 TCGA-09-1662 TCGA-10-0935 TCGA-61-2109 TCGA-13-1491 TCGA-13-0797 TCGA-09-1665 TCGA-10-0936 TCGA-61-2095 TCGA-13-1500 TCGA-13-0717 TCGA-09-1666 TCGA-10-0937 TCGA-61-2096 TCGA-24-1435 TCGA-13-0751 TCGA-09-1667 TCGA-10-0938 TCGA-61-2097 TCGA-13-1481 TCGA-13-0805 TCGA-09-1668 TCGA-13-0807 TCGA-61-2098 TCGA-24-1417 TCGA-13-0730 TCGA-09-1669 TCGA-13-0883 TCGA-61-2110 TCGA-13-1505 TCGA-13-0795 TCGA-24-1544 TCGA-13-0885 TCGA-61-2111 TCGA-13-1495 TCGA-13-0714 TCGA-24-1545 TCGA-13-0886 TCGA-61-2113 TCGA-13-1484 TCGA-13-0794 TCGA-24-1546 TCGA-13-0887 TCGA-61-2017 TCGA-13-1496 TCGA-13-0804 TCGA-24-1548 TCGA-13-0888 TCGA-61-2018 TCGA-13-1485 TCGA-13-0727 TCGA-24-1556 TCGA-13-0889 TCGA-61-2012 TCGA-24-1466 TCGA-13-0762 TCGA-24-1557 TCGA-13-0890 TCGA-61-2016 TCGA-24-1428 TCGA-09-0369 TCGA-24-1558 TCGA-13-0891 TCGA-61-2092 TCGA-24-1467 TCGA-13-0883 TCGA-24-1560 TCGA-13-0897 TCGA-61-2094 TCGA-24-1430 TCGA-10-0934 TCGA-24-1567 TCGA-13-0899 TCGA-61-2087 TCGA-24-1418 TCGA-13-0923 TCGA-25-1623 TCGA-13-0903 TCGA-61-2088 TCGA-13-1506 TCGA-13-0912 TCGA-25-1625 TCGA-13-0904 TCGA-61-1998 TCGA-24-1419 TCGA-13-0891 TCGA-25-1626 TCGA-13-0906 TCGA-61-2000 TCGA-13-1507 TCGA-23-2084 TCGA-25-1627 TCGA-13-0910 TCGA-61-1995 TCGA-13-1497 TCGA-13-0807 TCGA-25-1628 TCGA-13-0911 TCGA-61-2008 TCGA-13-1487 TCGA-13-0761 TCGA-25-1630 TCGA-13-0912 TCGA-61-2009 TCGA-24-1469 TCGA-13-0764 TCGA-25-1631 TCGA-13-0913 TCGA-61-2002 TCGA-24-1550 TCGA-23-2078 TCGA-25-1632 TCGA-13-0916 TCGA-61-2003 TCGA-24-1565 TCGA-13-0766 TCGA-25-1633 TCGA-13-0919 TCGA-59-2349 TCGA-24-1470 TCGA-23-2077 TCGA-25-1634 TCGA-13-0920 TCGA-59-2348 TCGA-24-1551 TCGA-23-2081 TCGA-25-1635 TCGA-13-0921 TCGA-59-2351 TCGA-24-1603 TCGA-23-2079 TCGA-36-1568 TCGA-13-0923 TCGA-59-2350 TCGA-24-1471 TCGA-13-0799 TCGA-36-1569 TCGA-13-0924 TCGA-59-2354 TCGA-24-1552 TCGA-13-0755 TCGA-36-1570 TCGA-24-0966 TCGA-59-2352 TCGA-24-1604 TCGA-13-0720 TCGA-36-1571 TCGA-24-0980 TCGA-61-1734 TCGA-24-1553 TCGA-23-2072 TCGA-36-1574 TCGA-04-1331 TCGA-61-1736 TCGA-24-1614 TCGA-13-0886 TCGA-36-1575 TCGA-04-1332 TCGA-59-2355 TCGA-04-1514 TCGA-13-0916 TCGA-36-1576 TCGA-04-1335 TCGA-59-2363 TCGA-24-1555 TCGA-10-0927 TCGA-36-1577 TCGA-04-1336 TCGA-29-2414 TCGA-24-1616 TCGA-10-0937 TCGA-36-1578 TCGA-04-1337 TCGA-29-2425 TCGA-04-1530 TCGA-13-0887 TCGA-36-1580 TCGA-04-1338 TCGA-29-2427 TCGA-24-1562 TCGA-13-0904 TCGA-36-1581 TCGA-04-1341 TCGA-29-2428 TCGA-07-0249 TCGA-13-0919 TCGA-57-1582 TCGA-04-1342 TCGA-25-1870 TCGA-24-1424 TCGA-61-1910 TCGA-57-1583 TCGA-04-1343 TCGA-61-1917 TCGA-13-1511 TCGA-61-1895 TCGA-57-1584 TCGA-04-1346 TCGA-31-1959 TCGA-13-1482 TCGA-61-1725 TCGA-57-1585 TCGA-04-1347 TCGA-30-1892 TCGA-24-1436 TCGA-04-1649 TCGA-04-1655 TCGA-20-0987 TCGA-61-1918 TCGA-13-1501 TCGA-24-1842 TCGA-09-1670 TCGA-20-0990 TCGA-57-1992 TCGA-13-1492 TCGA-29-1769 TCGA-09-1672 TCGA-20-0991 TCGA-31-1944 TCGA-24-1426 TCGA-61-1911 TCGA-09-1673 TCGA-20-0996 TCGA-30-1862 TCGA-13-1512 TCGA-61-1899

2 TCGA-09-1674 TCGA-23-1021 TCGA-31-1956 TCGA-13-1483 TCGA-61-1740 TCGA-09-1675 TCGA-23-1022 TCGA-30-1891 TCGA-24-1463 TCGA-23-1029 TCGA-20-1682 TCGA-23-1023 TCGA-30-1860 TCGA-13-1504 TCGA-24-1850 TCGA-20-1683 TCGA-23-1024 TCGA-24-2027 TCGA-13-1494 TCGA-61-1907 TCGA-20-1684 TCGA-23-1026 TCGA-30-1861 TCGA-24-1474 TCGA-04-1648 TCGA-20-1685 TCGA-23-1027 TCGA-24-1924 TCGA-24-1425 TCGA-61-1722 TCGA-20-1686 TCGA-23-1028 TCGA-61-1743 TCGA-24-1564 TCGA-61-1741 TCGA-20-1687 TCGA-23-1030 TCGA-57-1994 TCGA-24-1549 TCGA-23-1111 TCGA-23-1114 TCGA-23-1031 TCGA-30-1867 TCGA-09-1667 TCGA-04-1638 TCGA-23-1809 TCGA-23-1032 TCGA-31-1950 TCGA-25-1633 TCGA-30-1856 TCGA-24-1847 TCGA-23-1107 TCGA-30-1866 TCGA-25-1623 TCGA-61-1738 TCGA-29-1688 TCGA-23-1109 TCGA-31-1946 TCGA-36-1577 TCGA-29-1778 TCGA-29-1690 TCGA-23-1110 TCGA-25-1871 TCGA-24-1567 TCGA-24-1849 TCGA-29-1691 TCGA-23-1113 TCGA-24-1930 TCGA-24-1544 TCGA-61-1906 TCGA-29-1693 TCGA-23-1116 TCGA-25-1877 TCGA-24-1560 TCGA-04-1646 TCGA-29-1694 TCGA-23-1117 TCGA-57-1993 TCGA-25-1630 TCGA-30-1857 TCGA-29-1695 TCGA-23-1118 TCGA-61-1919 TCGA-04-1519 TCGA-24-2289 TCGA-29-1696 TCGA-23-1119 TCGA-61-1915 TCGA-25-1627 TCGA-24-2290 TCGA-29-1697 TCGA-23-1120 TCGA-61-1903 TCGA-36-1578 TCGA-10-0928 TCGA-29-1698 TCGA-23-1121 TCGA-61-1737 TCGA-04-1536 TCGA-13-0897 TCGA-29-1699 TCGA-23-1122 TCGA-30-1855 TCGA-09-1665 TCGA-13-0913 TCGA-29-1701 TCGA-23-1123 TCGA-24-1846 TCGA-25-1631 TCGA-13-0924 TCGA-29-1702 TCGA-23-1124 TCGA-29-1777 TCGA-57-1584 TCGA-10-0935 TCGA-29-1703 TCGA-24-0968 TCGA-04-1654 TCGA-36-1575 TCGA-13-0885 TCGA-29-1705 TCGA-24-0970 TCGA-61-1904 TCGA-04-1525 TCGA-13-0899 TCGA-29-1707 TCGA-24-0975 TCGA-24-1844 TCGA-24-1558 TCGA-10-0926 TCGA-29-1710 TCGA-24-0979 TCGA-29-1775 TCGA-09-1661 TCGA-10-0936 TCGA-29-1711 TCGA-24-0981 TCGA-61-1914 TCGA-09-1662 TCGA-10-0931 TCGA-29-1761 TCGA-24-0982 TCGA-61-1901 TCGA-09-1659 TCGA-13-0921 TCGA-29-1762 TCGA-24-1103 TCGA-61-1733 TCGA-25-1625 TCGA-13-0911 TCGA-29-1763 TCGA-24-1104 TCGA-09-1664 TCGA-36-1576 TCGA-13-0890 TCGA-29-1764 TCGA-24-1105 TCGA-24-1845 TCGA-24-1557 TCGA-24-0980 TCGA-29-1766 TCGA-04-1348 TCGA-29-1776 TCGA-25-1628 TCGA-10-0933 TCGA-29-1768 TCGA-04-1349 TCGA-31-1953 TCGA-25-1634 TCGA-20-0987 TCGA-29-1770 TCGA-04-1350 TCGA-61-1724 TCGA-36-1571 TCGA-13-0903 TCGA-29-1771 TCGA-04-1351 TCGA-24-1920 TCGA-57-1582 TCGA-13-0888 TCGA-29-1781 TCGA-04-1356 TCGA-24-2026 TCGA-04-1517 TCGA-10-0938 TCGA-29-1783 TCGA-04-1357 TCGA-30-1859 TCGA-24-1556 TCGA-13-0920 TCGA-29-1784 TCGA-04-1360 TCGA-30-1887 TCGA-04-1542 TCGA-13-0906 TCGA-29-1785 TCGA-04-1361 TCGA-61-1728 TCGA-24-1563 TCGA-24-0966 TCGA-30-1714 TCGA-04-1362 TCGA-24-1923 TCGA-04-1655 TCGA-10-0930 TCGA-30-1718 TCGA-04-1364 TCGA-24-2020 TCGA-29-1781 TCGA-13-0910 TCGA-57-1586 TCGA-04-1365 TCGA-25-1878 TCGA-29-1694 TCGA-13-0889 TCGA-04-1638 TCGA-04-1367 TCGA-31-1951 TCGA-20-1684 TCGA-24-0968 TCGA-04-1646 TCGA-04-1371 TCGA-61-1721 TCGA-29-1693 TCGA-20-0990 TCGA-04-1648 TCGA-13-0884 TCGA-10-0925 TCGA-20-1683 TCGA-23-1023 TCGA-04-1649 TCGA-13-0893 TCGA-24-2023 TCGA-29-1761 TCGA-04-1337 TCGA-04-1651 TCGA-13-0894 TCGA-30-1853 TCGA-29-1702 TCGA-23-1122 TCGA-04-1652 TCGA-13-0900 TCGA-30-1880 TCGA-30-1718 TCGA-13-2060 TCGA-09-1664 TCGA-13-0901 TCGA-04-1348 TCGA-29-1701 TCGA-24-0981

3 TCGA-23-1029 TCGA-13-0905 TCGA-09-2048 TCGA-57-1586 TCGA-23-1110 TCGA-23-1111 TCGA-13-0908 TCGA-09-2049 TCGA-29-1771 TCGA-23-1032 TCGA-24-1842 TCGA-13-1403 TCGA-04-1362 TCGA-23-1114 TCGA-23-1121 TCGA-24-1843 TCGA-13-1404 TCGA-09-2050 TCGA-36-1574 TCGA-24-0979 TCGA-24-1844 TCGA-13-1405 TCGA-25-1313 TCGA-29-1691 TCGA-23-1109 TCGA-24-1845 TCGA-13-1407 TCGA-09-2051 TCGA-20-1682 TCGA-23-1031 TCGA-24-1846 TCGA-13-1408 TCGA-25-1321 TCGA-24-1548 TCGA-04-1343 TCGA-24-1849 TCGA-13-1409 TCGA-13-0894 TCGA-36-1570 TCGA-23-1021 TCGA-24-1850 TCGA-13-1410 TCGA-13-1407 TCGA-57-1585 TCGA-04-1331 TCGA-29-1769 TCGA-13-1411 TCGA-09-2043 TCGA-09-1668 TCGA-23-1117 TCGA-29-1774 TCGA-13-1412 TCGA-09-2044 TCGA-20-1686 TCGA-04-1335 TCGA-29-1775 TCGA-24-1413 TCGA-25-1329 TCGA-29-1696 TCGA-24-0982 TCGA-29-1776 TCGA-25-1312 TCGA-09-2045 TCGA-29-1784 TCGA-23-1123 TCGA-29-1777 TCGA-25-1313 TCGA-04-1361 TCGA-09-1672 TCGA-24-1103 TCGA-29-1778 TCGA-25-1314 TCGA-13-1409 TCGA-29-1785 TCGA-23-1027 TCGA-30-1855 TCGA-25-1315 TCGA-25-1315 TCGA-09-1673 TCGA-23-1028 TCGA-30-1856 TCGA-25-1316 TCGA-04-1364 TCGA-29-1707 TCGA-04-1347 TCGA-30-1857 TCGA-25-1317 TCGA-13-0901 TCGA-29-1764 TCGA-23-1119 TCGA-61-1722 TCGA-25-1318 TCGA-25-1322 TCGA-29-1783 TCGA-23-1026 TCGA-61-1725 TCGA-25-1319 TCGA-09-2053 TCGA-09-1670 TCGA-04-1346 TCGA-61-1727 TCGA-25-1320 TCGA-09-2054 TCGA-29-1703 TCGA-23-1118 TCGA-61-1730 TCGA-25-1321 TCGA-04-1349 TCGA-29-1762 TCGA-04-1332 TCGA-61-1733 TCGA-25-1322 TCGA-09-2055 TCGA-29-1705 TCGA-23-1113 TCGA-61-1737 TCGA-25-1323 TCGA-13-0900 TCGA-29-1763 TCGA-20-0991 TCGA-61-1738 TCGA-25-1324 TCGA-09-2056 TCGA-20-1685 TCGA-24-0970 TCGA-61-1740 TCGA-25-1325 TCGA-25-1314 TCGA-29-1695 TCGA-23-1024 TCGA-61-1741 TCGA-25-1326 TCGA-04-1336 TCGA-61-1727 TCGA-61-1895 TCGA-25-1328 TCGA-23-1107 TCGA-04-1651 TCGA-61-1899 TCGA-25-1329 TCGA-23-1124 TCGA-24-1843 TCGA-61-1900 TCGA-13-1477 TCGA-24-1104 TCGA-29-1774 TCGA-61-1901 TCGA-13-1481 TCGA-23-1116 TCGA-61-1913 TCGA-61-1903 TCGA-13-1482 TCGA-20-0996 TCGA-61-1900 TCGA-61-1904 TCGA-13-1483 TCGA-24-0975 TCGA-61-1730 TCGA-61-1906 TCGA-13-1484 TCGA-04-1341 TCGA-04-1652 TCGA-61-1907 TCGA-13-1485 TCGA-25-1320 TCGA-24-2281 TCGA-61-1910 TCGA-13-1487 TCGA-25-1312 TCGA-24-2288 TCGA-61-1911 TCGA-13-1488 TCGA-24-1105 TCGA-24-2271 TCGA-61-1913 TCGA-13-1489 TCGA-23-1022 TCGA-24-2262 TCGA-61-1914 TCGA-13-1491 TCGA-04-1342 TCGA-24-2267 TCGA-61-1915 TCGA-13-1492 TCGA-23-1030 TCGA-24-2297 TCGA-09-0364 TCGA-13-1494 TCGA-04-1338 TCGA-24-2298 TCGA-09-0365 TCGA-13-1495 TCGA-23-1120 TCGA-24-2293 TCGA-09-0366 TCGA-13-1496 TCGA-13-0908 TCGA-24-2295 TCGA-09-0367 TCGA-13-1497 TCGA-13-1411 TCGA-25-2401 TCGA-09-0369 TCGA-13-1498 TCGA-25-1317 TCGA-25-2400 TCGA-13-0714 TCGA-13-1499 TCGA-25-1325 TCGA-25-2408 TCGA-13-0717 TCGA-13-1500 TCGA-25-1316 TCGA-25-2404 TCGA-13-0723 TCGA-13-1501 TCGA-25-1324 TCGA-25-2397 TCGA-13-0724 TCGA-13-1504 TCGA-04-1351 TCGA-25-2396 TCGA-13-0725 TCGA-13-1505 TCGA-04-1367 TCGA-25-2399

4 TCGA-13-0726 TCGA-13-1506 TCGA-13-1408 TCGA-25-2398 TCGA-13-0727 TCGA-13-1507 TCGA-24-1416 TCGA-25-2409 TCGA-13-0730 TCGA-13-1509 TCGA-24-1427 TCGA-25-2042 TCGA-13-0757 TCGA-13-1510 TCGA-24-1464 TCGA-25-2391 TCGA-13-0758 TCGA-13-1511 TCGA-04-1356 TCGA-25-2392 TCGA-13-0760 TCGA-13-1512 TCGA-04-1371 TCGA-25-2393 TCGA-13-0761 TCGA-24-1416 TCGA-13-1403 TCGA-24-2019 TCGA-13-0762 TCGA-24-1417 TCGA-13-1412 TCGA-24-2024 TCGA-13-0764 TCGA-24-1418 TCGA-25-1318 TCGA-24-2033 TCGA-13-0768 TCGA-24-1419 TCGA-13-1410 TCGA-24-2030 TCGA-13-0791 TCGA-24-1422 TCGA-04-1357 TCGA-24-2035 TCGA-13-0792 TCGA-24-1423 TCGA-25-1326 TCGA-24-2254 TCGA-13-0793 TCGA-24-1424 TCGA-04-1350 TCGA-24-2038 TCGA-13-0794 TCGA-24-1426 TCGA-25-1323 TCGA-24-2261 TCGA-13-0795 TCGA-24-1427 TCGA-13-0905 TCGA-24-2260 TCGA-13-0800 TCGA-24-1428 TCGA-04-1365 TCGA-13-0723 TCGA-13-0801 TCGA-24-1430 TCGA-04-1360 TCGA-13-0757 TCGA-13-0802 TCGA-24-1431 TCGA-25-1328 TCGA-13-0768 TCGA-13-0803 TCGA-24-1434 TCGA-13-1405 TCGA-13-0800 TCGA-13-0804 TCGA-24-1435 TCGA-13-0893 TCGA-13-0758 TCGA-13-0805 TCGA-24-1436 TCGA-13-1404 TCGA-09-0364 TCGA-13-0720 TCGA-24-1463 TCGA-13-0884 TCGA-13-0726 TCGA-13-0751 TCGA-24-1464 TCGA-25-1319 TCGA-09-0367 TCGA-13-0755 TCGA-24-1466 TCGA-24-1413 TCGA-13-0803 TCGA-13-0765 TCGA-24-1467 TCGA-13-1488 TCGA-13-0793 TCGA-13-0766 TCGA-04-1514 TCGA-13-1498 TCGA-13-0792 TCGA-13-0797 TCGA-04-1530 TCGA-24-1431 TCGA-13-0760 TCGA-13-0799 TCGA-04-1542 TCGA-13-1477 TCGA-13-0802 TCGA-10-0926 TCGA-04-1517 TCGA-24-1434 TCGA-13-0801 TCGA-10-0927 TCGA-04-1519 TCGA-13-1509 TCGA-13-0725 TCGA-10-0928 TCGA-04-1525 TCGA-24-1422 TCGA-09-0366 TCGA-10-0930 TCGA-13-1510 TCGA-09-0365

5 Supplementary Figure S1. Identification of EMT target genes

Supplementary Fig.S1. Derivation of the 39 metastases - associated gene signature. A,B.Pearson correlation (r) maps of EMT related transcription factors using Affymetrix data (A; - 0.5

6 Supplementary Table 2: List of EMT-TF targets and LPA-S1P signaling components

Snail-Slug-Twist (EMT) Target Genes LPA-S1P signaling mediated events 99 61 ACCN3 EN1 KCND3 ADCY1 LPAR3 ACF F10 KCNK12 ADCY2 LPAR4 ADRA2B FAM19A4 KCNK17 ADCY3 LYN ALDH3A1 FBXL21 KEL ADCY4 MAPT APBB1IP FCN2 KLHL1 ADCY5 MMP2 AQP4 FGF19 MAS1L ADCY6 MMP9 ASCL2 FGF6 MASP1 ADCY7 PIK3R1 B3GALT2 FGF8 MMP14 ADCY8 PLCB3 BCL2L14 FLT3 MTNR1A ARHGEF1 PLCG1 BHMT FOXR1 MYH11 BCAR1 PLD2 BOLL FSTL4 NOL4 CASP3 PRKCD CACNA2D1 GALR1 NPPC CRK PRKCE CALCA GDAP1 NPY5R EGFR PRKD1 CAMK2A GIMAP1 NXPH2 FOS PTK2 CARD11 GLULD1 OTP GAB1 PTK2B CCL16 GNA15 PAEP GNA11 PXN CDH1 GNMT PDE6H GNA12 RAC1 CH25H HAND1 PEX5L GNA13 RELA CHST9 HCG3 PGLYRP2 GNA14 RHOA CIDEB HES5 PHOX2B GNA15 S1PR1 CK18 HGFAC PPEF2 GNAI1 S1PR2 CK8 HIC1 PRDM14 GNAI2 S1PR3 COL2A1 HOXA4 PRTFDC1 GNAZ S1PR4 CRHR2 HTR3E RET GNB1 S1PR5 CRTAC1 HTR6 RLN3 GNG2 SLC9A3R2 CSMD2 IL13 SCN7A GSK3B SRC CTNND2 IL17B SERPINB11 HBEGF TIAM1 CYB5R2 IL2RA SLC1A2 HRAS TRIP6 CYSLTR2 IL3 SLC9A3 IL6 DGKI INHA ST6GALNAC5 IL8 ECEL1 IRX6 TAS2R38 JUN ELAVL3 ITGA8 TMEM16A LPAR1 EMID2 ITIH2 VIP LPAR2

7 Supplementary Figure S2. Tumor classification by M-classification approach.

A. i) K=2 ii) K=3 iii) K=4

B. i) K=2 ii) K=3 iii) K=4

C. PCA D. BGA E. Overlap of Silhouette and Consensus clustering

Supplementary Fig.S2. Tumor classification by M-classification approach. A. Silhouette clustering plots of samples from k-mean values k=2 to k=4 respectively; B. Consensus clustering from k-mean values k=2 to k=4 respectively. C. Principle component analysis (PCA) supervised classification shows three distinct clusters with projection of samples represented in different colors. Axis 1 (horizontal) is the discriminator between class1 (red) from the Class 2 and Class 3; while axis 2 (vertical) discriminates Class 3 from the others two classes. D. Between group analysis (BGA) depicting 39 gene expression profiles in 3 clusters E. Overlap of samples from Silhouette clustering and Consensus clustering approached results into core sample distribution as – Class2 (n=97), Class 2 (n=119) and Class 3 (n=70).

8 Supplementary Figure S3. Derivation of the 39 metastases-associated gene set

Supplementary Fig.S3. Derivation of 39 metastases associated gene set. A. Pearson Correlation map of 99 EMT target genes (-0.51) carried out for 99-EMT targets and 61 LPA-S1P receptor events (- 0.4>r>0.4, p<0.05)

9 Supplementary Table 3. Literature based functional assignment of the 39 gene set with metastases

Gene Reference PMID JUN Ponnusamy et al. Oncogene. 2010 Oct 21;29(42):5741-54. 20697346 ACCN3 - - ACF** Nelson et al. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):E2766-73. 22923694 ADCY4 - - ADCY7 - - APBB1IP* Hernández-Varas et al. J Biol Chem. 2011 May 27;286(21):18492-504. 21454517 CARD11** Blonska M, Lin X. Cell Res. 2011 Jan;21(1):55-70. 21187856 CH25H* Dutton-Regester et al. Genes Chromosomes Cancer. 2012 May;51(5):452-61. 22250051 COL2A1* Vincourt et al. Cancer Res. 2010 Jun 1;70(11):4739-48. 20460531 ECEL1* Granchi et al. Prostate. 2001 Dec 1;49(4):267-77. 11746273 EDG1 Fang et al.Ann N Y Acad Sci. 2000 Apr;905:188-208. 10818454 EDG6* Becker et al. Biol Reprod.2011 Mar;84(3):604-12. 20980685 EN1** Montavon et al. Gynecol Oncol. 2012 Mar;124(3):582-8. 22115852 FBXL21 - - FGF19* Wang et al. J Clin Invest. 2011 Aug;121(8):3220-32. 21747170 FOS Ma et al. Int J Gynecol Cancer. 2011 May;21(4):616-24. 21543928 GALR1* Louridas et al. Biochem Biophys Res Commun. 2009 Dec 18;390(3):867-71 19840773 GDAP1** Ratajewski M, Pulaski L. Genomics. 2009 Dec;94(6):407-13. 19720140 GIMAP1** Krücken et al. Gene. 2004 Oct 27;341:291-304. 15474311 GNA13* Rasheed et al. J Biol Chem. 2013 Mar 15;288(11):7986-95. 23329838 GNA15* de Jonge et al. Leukemia. 2011 Dec;25(12):1825-33 21760593 GNAI1** Yao et al. Cancer Biol Med. 2012 Dec;9(4):234-41. 23691483 GPR23* Lee et al. Mol Biol Cell. 2008 Dec;19(12):5435-45. 18843048 HAND1* Martinez et al. Oncogene. 2009 Feb 12;28(6):876-85. 19060921 HBEGF* Bos et al. Nature. 2009 Jun 18;459(7249):1005-9. 19421193 HGFAC* Parr C, Jiang WG. Int J Cancer. 2006 Sep 1;119(5):1176-83. 16557597 IL2RA Bamias et al. Gynecol Oncol. 2007 Jul;106(1):75-81. 17433425 IL6 Giridhar et al. Clin Exp Metastasis. 2011 Dec;28(8):887-97 21887537 IL8 Wang et al. Cytokine. 2012 Jul;59(1):145-55. 22579115 ITIH2* Hamm et al. BMC Cancer. 2008 Jan 28;8:25. 18226209 KCNK12* Kober et al. Mol Carcinog. 2011 Nov;50(11):846-56. 21438024 KRT18 Tafe et al Mod Pathol. 2010 Jun;23(6):781-9. 20305618 KRT8 Khapare et al. PLoS One. 2012;7(6):e38561 22701666 MMP14 Moss et al. Cancer Res. 2009 Sep 1;69(17):7121-9. 19706774 MMP2 Kenny et al. J Clin Invest. 2008 Apr;118(4):1367 18340378 MMP9 Yan et al. Zhonghua Zhong Liu Za Zhi. 2002 Jan;24(1):17-9. 11977628 PRKD1 - - PRTFDC1 - - RHOA Wu et al. Tumour Biol.2012 Oct;33(5):1619-28. 22610942 10 Supplementary Data1. Weighted gene co-expression network analysis (WGCNA) and module identification (W-classification)

Median absolute deviation (MAD) was applied across the expression dataset to eliminate unreliable genes and limit analysis to relevant genes. Thereby 17813 genes on the platform were reduced to 6840 genes (each gene expressing a minimum 1.5 fold difference with its median value in at least 20% of samples at log intensity variation p <0.05). These 6840 highly variable genes were used in WGCNA for 359 tumor sample; network analysis was performed as described earlier (Ghazalpour et al.2006). For each set of genes, a pair-wise Pearson correlation matrix was computed. Adjacency matrix was calculated by raising the power (β=6) of correlation matrix, producing weighted correlation matrix (Adjacency matrix=Correlation matrix6); Beta (β) values selected using Scale free topology approach (R2 curve level highest at β=6 with R2=0.95). Using adjacency matrix, a network of topological overlap (TO) was calculated. Genes were clustered through average linkage hierarchical clustering using TO as input. 13 Modules (clusters of highly co-expressed genes) were identified on the dendrogram using Dynamic Tree Cut algorithm (Data1.Fig.1A). To resolve moderately large and distinct modules, minimum module size set was at 30 and minimum height for merging modules was kept at 0.25. A condensed and representative form for each module (Module eigengene, ME) was calculated using PCA. Core genes from each module was identified based on correlation between ME value of particular module and expression profile of gene in that module (Table S1). Top 25 representative genes were extracted from each module which had highest correlation with ME value of that module for performing k-means clustering using MeV.v4 software (Multi Experiment Viewer) at k=3. Thereby the 359 tumor samples were grouped into 3 clusters based on top 25 genes from 13 modules (Data1.Fig.1B). Further information on network analysis and WGCNA software as applied in this analyses is available at - www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork.

Data1.Fig.1A. Representative TOM plot. B. k-mean clustering using Top 50 genes and 359 samples.

11 Effectively, WGCNA involves identification of co-expressed modules based on similarity measure. In our analysis, the similarity (sij) were measured based on absolute value of correlation coefficient between two gene profiles as i and j as –

sij = |cor(xi, xj)| in which correlation values at both extremes, viz. positive (+1) or negative (-1) are truncated between a range of 0 to 1.

Module nomenclature is assigned by WGCNA in a descending manner, thus M1 is the largest sized module and contained highly correlating genes, while M13 had the least number of genes. Expression profiling further indicated the subsistence of two subgroups that were anti- correlative; we resolved these two as M1a and M1b of which M1a genes had high positive correlation with module eigengene, while M1b genes correlated negatively with module eigengene.

Data1.Table 1: Modules - corresponding genes in W-classification W-Classification Color of the module in Fig. 2a Module No. No. of Genes (above) M0 2635 grey M1 1242 turquoise M2 631 blue M3 620 brown M4 515 yellow M5 315 green M6 235 red M7 254 black M8 106 pink M9 124 magenta M10 41 purple M11 44 Green-Yellow M12 41 tan M13 37 salmon

Overlap of M- classification scheme and W-classification schemes

Data1.Fig.2 Representative WGCNA module enrichment in Core tumor samples; red and green triangles indicate upregulated and downregulated modules respectively

12 A striking feature that was observed related to the similar distribution of specific tumor samples in the two classification schemes. This encouraged us to extract the core samples through an overlap of two approaches (also refer Main manuscript Fig.4; p-value < 2.2*10-16, Fisher exact test). Comparative median expression profile graph (Data1.Fig.2) of these overlapped samples (Class1 with 77 samples, Class2 with 99 samples and Class3 with 51 samples) with top 50 genes of each module were plotted for identification of highly differential modules across the classes.

Distribution of the 39 metastases genes in the 13 WGCNA-classification modules

The 39 metastases gene signature was seen to be distributed in modules M0, M1b, M2, M3, M4, M5 and M11 as below –

Data1.Table2: Distribution of 39 metastases gene in modules

M0 M1b M2 M3 M4 M5 M11 GNAI1 ADCY4 GNA13 CH25H - PRTFDC1 - APBB1IP FOS LPA-S1P targets EDG6 MMP14 (Activated due to GIMAP1 MMP2 signaling) IL2RA PRKD1 IL6 MMP9 ECEL1 GNA15 - GPR23 ITIH2 - COL2A1 GDAP1 HBEGF KCNK12 KRT8 IL8 ACCN3 KRT18 ACF EMT Targets JUN CARD11 (known to be EN1 repressed by FBXL21 EMT-TFs) FGF19 GALR1 HAND1 HGFAC EDG1

None of the genes from this signature were present in the Class1-enriched modules (M1a,M6,M11); but were associated with Class2 enriched modules (M1b,M3) and Class3 enriched modules (M2,M4). Thus Class2 and Class3 are suggested to be associated with EMT- LPA-S1P mediated metastases.

References –

1. Ghazalpour A, Doss S, Integrating Genetic and Network Analysis to Characterize Genes Related to Mouse Weight, PloS genetics (2006), 10.1371/journal.pgen.0020130. 2. Monti, S., Tamayo, P., Mesirov, J., Golub, T. (2003) Consensus Clustering: A Resampling-Based Method for Class Discovery and Visualization of Gene Expression Microarray Data. Machine Learning, 52, 91:118.

13 Supplementary Data 2. Classification and module gene validation in additional Ovarian Cancer datasets (VDs)

The subsistence of 3 serous ovarian cancer classes as identified in the TCGA Agilent dataset was further validated in seven other serous ovarian cancer expression datasets (VDs) available in the public domain (Gene Expression Omnibus-GEO; http://www.ncbi.nlm.nih.gov/geo) -

Data2.Table 1: Serous Ovarian cancer datasets used for validation

Sr. Selected Genes and Platform Reference no. Patient Samples VD1 Affymetrix HG-U133A 4864 genes, 512 samples TCGA-Affymetrix VD2 Affymetrix HG-U133 4848 genes, 80 samples GSE14764 VD3 Affymetrix HG-U133 plus 2 6433 genes, 53 samples GSE18520 VD4 Affymetrix HG-U133 plus 2 6441 genes, 65 samples GSE20565l VD5 Affymetrix U95AV2 3592 genes, 42 samples GSE19829 Agilent Whole Human Genome Oligo VD6 6292 genes, 110 samples GSE17260 microarray VD7 Operon human v3 Oligo microarrays 5921 genes, 415 samples GSE13876

1. VD2: GSE14764: Denkert C, Budczies J, Darb-Esfahani S, Györffy B et al. A prognostic gene expression index in ovarian cancer - validation across different independent data sets. J Pathol 2009 Jun;218(2):273-80. 2. VD3: GSE18520: Mok SC, Bonome T, Vathipadiekal V, Bell A et al. A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2. Cancer Cell 2009 Dec 8;16(6):521-32. 3. VD4: GSE20565: Meyniel JP, Cottu PH, Decraene C, Stern MH et al. A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer. BMC Cancer 2010 May 21;10:222. 4. VD5: GSE19829: Konstantinopoulos PA, Spentzos D, Karlan BY, Taniguchi T et al. Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. J Clin Oncol 2010 Aug 1;28(22):3555-61. 5. VD6: GSE17260: Yoshihara K, Tajima A, Yahata T, Kodama S et al. Gene expression profile for predicting survival in advanced-stage serous ovarian cancer across two independent datasets. PLoS One 2010 Mar 12;5(3):e9615. 6. VD7: GSE13876: Crijns AP, Fehrmann RS, de Jong S, Gerbens F et al. Survival-related profile, pathways, and transcription factors in ovarian cancer. PLoS Med 2009 Feb 3;6(2):e24.

Initially, significance of the 39 metastases-associate gene signatures in these VDs was validated using unsupervised PCA and supervised BGA clustering. This gene signature indeed effectively exhibited potential to classify ovarian tumor samples into 3 distinct groups. Next, in order to validate the significance of WGCNA modules, k-mean clustering was performed using Top 50 genes from M1a, M1b, M2, M3, M4, M6, M9, and 44 genes from M11 (n=394) at k=3. M1a, M6 and M11 up-regulated expression was representative of Class1; that of M1b, M3 and M9 for Class2; and M2, M4 for Class3. Similarly, silhouette clustering for individual class was carried out with the enriched module genes followed by hierarchical clustering. A final representative heat-map exhibited the class-specific grouping of samples (Data2.Fig.1). While the Class1 and Class2 modules-associated genes validated, M2, M4 in Class3 profiles could not define Class3 in a significant manner.

14

A. VD1 B. VD2 C. VD3 132 132 123

M11 M6 M11 M11 M1a M6 M6 M1a M1a M M1b 1 M1b M1b M M3 3 M3 M3 M M4 M4 M4 M4 M9 9 M9 M9 M2 M2 M2 44 102 59 17 36 8 61315

D. VD4 E. VD5 F. VD6

2 132 13 2 13

M11 M11 M11 M6 M6 M6 M1a M1a M1a M1b M1b M1b M3 M3 M3

M4 M4 M4

M9 M9 M9

M2 M2 M2

9148 10 11 3 10 46 16

G. VD7 Data2.Fig. 1. Validation of 39 metastasis genes and Top 50 genes from significant modules in 7 SEOC gene 132 expression datasets (VDs). For each VD, PCA and BGA analysis were done using the 39 metastases-associated M11 gene signature and heat maps were generated using top M6

M1a 50 genes from significant enriched modules in the three M1b tumor classes (M1a,M6,M11 in Class1; M1b,M3,M9 in

M3 Class2 and M2,M4 in Class3)

M4

M9

M2

62 61 46

Module preservation study analysis

Studying module preservation is important to establish module conservation or stability across different datasets. Module assignment depends on differences in platforms and sample number variations. We carried out clustering of data in other SEOC validation datasets (VD1 – VD7) into different network modules based on the predicted module – class association as described earlier (http://www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork/ModulePreservation/Tutorials/). Network based module preservation was assessed in these datasets using Z statistics and medianRank statistics as composite preservation parameters. The threshold for Z summary and medianRank statistics was applied as described in Langfelder et al (2011), i.e. (i) Zsummary > 10 suggestive of strong module preservation; (ii) 2< Zsummary <10 suggests weak to moderate evidence of preservation, (iii) Zsummary <2, there is no evidence of module preservation, (iv) medianRank statistics value < 10 suggests high preservation and (v) medianRank statistics value > 10 is indicative of weak preservation.

15 Data2Fig.2. Composite preservation statistics of Agilent modules in all Validation dataset (VDs) modules. Each point represents a module, labelled by color and a secondary numeric label (1 = turquoise, 2 = blue, 3 = brown, 4 = yellow, 5 = green, 6 = red, 7 = black, 8=pink, 9= magenta, 10= purple, 11= greenyellow, 12= tan, 13= salmon). The dashed blue and green lines indicate the thresholds Z~2 and Z~10, respectively. Two composite statistics medianRank and Zsummary were plotted on y-axis as a function of module size on x-axis. 2

A high Z summary score and low medianRank value indicate stronger preservation while low Z summary score and higher medianRank value indicate weak preservation of modules. Further information on module preservation and R codes areavailable at- http://www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork/ModulePreservation/Tutorials/. The potential of Module M1, M3, M6 and M11 genes as signatures for identification of Class1 and Class2 samples thus validated as in the TCGA Agilent data, by exhibiting considerable preservation in other validation datasets (Data2.Figs.2 & 3; Data2.Table 2)

Data2- Table 2: Zsummary and medianRank results in Agilent and Validation datasets.

MedianRank results Zsummary results M1 M3 M6 M9 M11 M1 M3 M6 M9 M11 VD1           VD2        x   VD3 x x x        VD4           VD5   x     x   VD6           VD7 x       x  X “” in table indicate module gets preserved in Agilent and corresponding dataset and “x” represent weak preservation of module. Abbreviations used:”M”=module, “VD”=Validation dataset

16

Data2.Fig.3. Z summary (red bars) and medianRank (green bars) statistics between TCGA Agilent and validation datasets; a high Z summary score and low medianRank value indicate stronger preservation while low Z summary score and higher medianRank value indicate weak preservation of module

17 Data 3. Identification of class-defining features using Gene Set Enrichment Analysis (GSEA) Towards a functional analyses of the two tumor classes identified, we performed Gene Set Enrichment Analysis (GSEA; the Broad Institute;19) to identify enriched gene sets at p-value <0.1 and q-value <0.25. Class comparison networks were visualized using Enrichment map in Cytoscape_v2.8.2. Application of GSEA indeed did identify some biological processes and signaling pathways (p<0.05; FDR<0.25; Data3.Fig.1; Data3. Table1). Disease pathways and cardiomyopathy associated gene sets were enriched in both classes; however, since none of the genes in these pathways are shared between classes, activation of different components of the same pathway leading to different biological outcomes in the two classes is possible. Class1 exclusive pathways include signaling (Focal adhesion, PDGF, SHH), differentiation- developmental (NCAM, SHH, Osteoclast differentiation), Toll receptor cascades, cell-cell interactions, platelet deregulation-activation, etc.; while metabolism and signaling (chemokines, interferons and MAPK-GPCR) events were enriched in Class2.

Signaling Pathways MAPK-GPCR signalling

Signaling in pathways

Class 1 Class 2 Shared Genes Developme Cardiomyopathy ntal & Differentia Metabolism

tion

Cell-Cell Cell Junctions Interacti ons Immuno Hemostasis Pathways Pathways

Disease Pathways

Data3.Fig.1. GSEA based functional identities for tumor classes visualized as an Enrichment Map Network; each network node of Class1 and Class2 (red and blue respectively) represents enriched pathway (p<0.05; FDR cut-off <0.25). The connecting green line between two pathways (nodes) indicates shared genes; line thickness represents number of shared genes.

18 Data3.Table1. GSEA enriched pathways*

Class 1

Signaling B CELL RECEPTOR SIGNALING PATHWAY%KEGG%HSA04662, BTK, LILRB3, CCR5, ITGA11, GPR65, THBS1, FN1, Pathways SIGNALING PATHWAYS%REACTOME%REACT_111102.1, LAMA1, EDN3, LAMA2, COL5A2, COL5A1, GNA14, PATHWAYS IN CANCER%KEGG%HSA05200, FOCAL COL6A3, APBB1IP, PDGFRB, ARHGDIB, COL11A1, ADHESION%KEGG%HSA04510, SIGNALING BY COL4A6, TCF7L1, COL6A2, RGS18,PSMB8, COL9A3, PDGF%REACTOME%REACT_16888.1, HEDGEHOG SIGNALING PSMB9, CXCL11, RGS7, COL3A1, BMP6, COL1A2, PATHWAY%KEGG%HSA04340, COL2A1,GPR18,COL1A1,ITGB2,FBN1, AGTR1, SMO, ADAM12, C3AR1, MMP2, THBS2, GLI1, CASR, FGF1

Developmental & NCAM SIGNALING FOR NEURITE OUT-GROWTH Differentiation %REACTOME%REACT_18334.1, NCAM1 INTERACTIONS COL5A2, COL5A1, COL3A1, COL1A2, COL9A3, Pathways %REACTOME%REACT_18312.1, BIOCARTA_SHH_ COL2A1, COL6A3, COL6A2, COL1A1, GLI1, SMO, PATHWAY%MSIGDB_C2%BIOCARTA_SHH_PATHWAY, CYBB, BTK, CTSK, LILRB3, NCF2, NCF1, LCP2 OSTEOCLAST DIFFERENTIATION%KEGG%HSA04380,

Cell-Cell REGULATION OF ACTIN CYTOSKELETON %KEGG% Interactions HSA04810, INTEGRIN CELL SURFACE INTERACTIONS ITGA11, PDGFRB, ENAH, FN1, FGF1, ITGB2, FBN1, %REACTOME%REACT_13552.1, ECM-RECEPTOR THBS1, LAMA1, COL1A2, LAMA2, COL2A1, APBB1IP, INTERACTION%KEGG%HSA04512, CELL SURFACE COL1A1, COL3A1, COL11A1, COL5A2, COL5A1, INTERACTIONS AT THE VASCULAR WALL%REACTOME COL4A6, THBS2, COL6A3, COL6A2, CD48, CD2, %REACT_12051.1,

Hemostasis PLATELET DEGRANULATION% REACTOME% REACT_ 318.7, Pathways HEMOSTASIS%REACTOME%REACT_604.4, PLATELET SPARC, PLEK, THBS1, FN1, CD48, COL1A2, GATA4, ACTIVATION, SIGNALING AND AGGREGATION% REACTOME% LCP2, COL1A1, ITGB2, CD2, GNA14, APBB1IP, KIF9, REACT_798.4, RESPONSE TO ELEVATED PLATELET CYTOSOLIC CA2+%REACTOME%REACT_1280.3,

Disease Pathways BLADDER CANCER%KEGG%HSA05219, RHEUMATOID MMP2, THBS1, CTSK, TNFSF13B, TLR2, TLR4, ARTHRITIS%KEGG%HSA05323, AMOEBIASIS% KEGG% ITGB2, COL3A1, COL1A2, LAMA1, COL2A1, LAMA2, HSA05146, TUBERCULOSIS%KEGG%HSA05152, SMALL CELL COL1A1, COL11A1, COL5A2, COL5A1, GNA14, LUNG CANCER%KEGG%HSA05222, CHAGAS DISEASE COL4A6, FN1, CAMK2B, THBS2, CYBB, TAP1, (AMERICAN TRYPANOSOMIASIS)% KEGG% HSA05142, TUBB2B, NCF2, NCF1, COLEC11, GLI1, TCF7L1, MALARIA%KEGG%HSA05144, PHAGOSOME %KEGG SMO %HSA04145, BASAL CELL CARCINOMA% KEGG% HSA05217,

Immuno Pathways BIOCARTA_DC_PATHWAY%MSIGDB_C2%BIOCARTA_DC_PAT HWAY, TOLL LIKE RECEPTOR 4 (TLR4) CASCADE % REACTOME %REACT_6894.4, ACTIVATED TLR4 SIGNALLING %REACTOME%REACT_6890.6, BIOCARTA_ LAIR_ PATHWAY %MSIGDB _C2%BIOCARTA_LAIR_PATHWAY, TOLL LIKE RECEPTOR TLR6:TLR2 CASCADE% REACTOME% REACT TLR2, TLR4, CD33, CD2, C7, ITGB2, _8006.4, TOLL LIKE RECEPTOR TLR1:TLR2 CASCADE% REACTOME% REACT_8005.4, BIOCARTA_TOLL_PATHWAY %MSIGDB _C2%BIOCARTA_TOLL_PATHWAY, TOLL LIKE RECEPTOR 2 (TLR2) CASCADE %REACTOME %REACT _7980.5, MYD88:MAL CASCADE INITIATED ON PLASMA MEMBRANE%REACTOME%REACT_6788.5,

19

Class 2

MAPK-GPCR PEPTIDE LIGAND-BINDING RECEPTORS% REACTOME signalling %REACT_14819.2, LEUKOCYTE TRANSENDOTHELIAL pathways MIGRATION%KEGG%HSA04670, CLASS A/1 (RHODOPSIN-LIKE RECEPTORS)% REACTOME% REACT_14828.1, GPCR LIGAND BINDING%REACTOME AGTR1, CCR5, C3AR1, EDN3, CXCL11, MMP2, %REACT_21340.1, GPCR DOWNSTREAM SIGNALING CYBB, NCF2, NCF1, CLDN19, ITGB2, GPR65, %REACTOME%REACT_19184.3, MAPK SIGNALING GPR18, CASR, SMO, GNA14, RGS7, RGS18, PATHWAY%KEGG%HSA04010, CHEMOKINE PTPN5, PDGFRB, CACNA2D2, FGF1, HCK, SIGNALING PATHWAY% KEGG% HSA04062, G ALPHA (Q) SIGNALLING EVENTS% REACTOME% REACT_ 18283.4, SIGNALING BY GPCR %REACTOME %REACT _14797.1,

Cardiomyopathy BIOCARTA_CARDIACEGF_PATHWAY%MSIGDB_C2%B IOCARTA_CARDIACEGF_PATHWAY, CARDIAC AGTR1, ADAM12, MYH7, MYH6, CACNA2D2 MUSCLE CONTRACTION%KEGG%HSA04260

Metabolism INTEGRATION OF ENERGY METABOLISM% REACTOME%REACT_1505.2, FACTORS INVOLVED IN MEGAKARYOCYTE DEVELOPMENT AND PLATELET GNA14, CACNA2D2, GATA4, KIF9, HSD11B1, PRODUCTION%REACTOME%REACT_24970.1, STAR, STEROID HORMONES%REACTOME%REACT_15493.1, REGULATION OF INSULIN SECRETION% REACTOME %REACT_18325.3,

Cell Junction GAP JUNCTION%KEGG%HSA04540,CELL-CELL TUBB2B, PDGFRB, FYB, CDH11, CLDN19 COMMUNICATION%REACTOME%REACT_111155.1

Signaling in INTERFERON SIGNALING% REACTOME %REACT IFIT3, IFIT1, IFIT2, MX1, XAF1, DDX58, CAMK2B, Immune _25229.1 ISG15, OAS3, OAS1, OAS2, HERC5, UBE2L6, system OASL, IFI35, GBP4, PSMB8, GBP1

Significantly enriched pathway gene sets were compiled at significant level of p < 0.05 and FDR cut-off <0.25.

20 Supplementary Table 4: Modules and associated Genes Module 1a - 265 genes

SRCRB4D RP4-691N24-1 APOA1 LECT1 ATP1A2 CYTL1 NACAD GDF10 DDX25 CPA1 TBX1 KAZALD1 ST6GALNAC3 GPC1 CLDN19 CHST10 SERF1A WNT2B FXYD1 MSX1 CCNJL ENAH CA14 PRTG MTTP LTBP4 LRTM2 JARID1B USH1C LRP4 KCNJ13 LIN28B MYO15A CUTL2 GNAZ PURG SOX12 SLC13A4 PEG10 ADD2 ITM2C CABLES2 WDR54 MEX3A FKBP1B LASS4 H2AFY2 SALL1 ZFHX2 ZNF10 MAPK4 ODC1 CD320 SERPINB5 SLC16A12 IGSF9 HHATL CXXC6 DNASE1 ISYNA1 LRAT GREB1 SEMA6C TSPAN19 AZI1 TRIM63 SNIP CCKBR TYRO3 CHTF18 CAMK2B ZNF594 WASF1 MYH7B GLYATL1 ZIM2 CBX1 ZNF660 PCDHB9 ATP7B COL18A1 MAGED4B NANOG CCNJ TEX101 EPB49 VAX2 CCDC8 TRO TAS2R10 PLCB1 KIF1A GLI2 GPR98 GLT25D2 NOVA1 ABAT SPINK5 ZNF423 PCM1 SLC35F1 FGFR3 CDH2 GPT2 SLC5A12 COL9A3 GPM6A POPDC3 FGFR1 ARNT2 CHD7 ZNF676 MST1 DYNC2H1 PAFAH1B3 CDON FRAS1 SLC4A8 GPLD1 KCNC1 ICA1L RP11-35N6-1 FXYD6 ADAMTS3 SLC24A5 SULT1C4 JARID2 ARHGEF4 RPRM UNC93A TMEM178 ZNF334 ZNF84 LRP6 DDAH1 FANCC ATP6V1E2 MEST PLCB4 CCNB1IP1 SORBS2 CCL27 JMJD2D GDF11 REEP2 CECR2 PLCH1 CELSR3 ALDH3A1 BMP7 TMEM16B COL4A6 RAVER2 DLX4 PLXNA4A TP53TG3 NAP1L1 USP52 GLS2 MATN4 KCNJ12 SLC6A13 TUB PFKM ATOH7 PDE8B ABTB2 RAB11FIP2 SASP ZNF219 BFSP1 PNMT IL17RD LHX1 PAIP2B LAMA1 PRR6 SAMD11 CORO2B TMEM132B DNAH2 ZBED3 SLC10A4 FKBP6 IGFBP5 SORCS1 OBSL1 SALL2 GALNTL1 SELV PCP4 TMEM28 CLSTN3 ASXL3 SLC30A3 ATP4A SAMD13 GSTM3 CCDC77 PHF21B TMSL8 FSD1 ADARB2 BAMBI KIF7 MYH7 DPF1 GSTM2 WDR35 FGF9 ZNF512B PHC1 GPC3 PBX4 LGR5 SEMA6A RGL3 KCNIP3 MYCN TRIM45 TRIM43 ADAMTS19 EPOR BSN ENO2 IGF2BP3 ANKRD7 KCNG1 KRI1 SMO OVOS2 KLHL23 DMKN CRMP1 SMARCA4 CACNA2D2 PFKFB4 IL28RA KRTDAP THBS4 GEFT B4GALNT4 PPFIA4 NPM2 GCSH ZCCHC12 SLC26A10 MYH6 GALNT8 CAMKV MOSC1 ASTN1 APBA2 TCF7L1 CRIP3 NAP5 LEFTY2 SP5 ANKRD13B TUBB2B PRSS3 TESC FBXO17 BEX1 SLC4A3

21 S.Table 3(Cont’d) Module 1b - 976 genes LCP2 CD33 AOAH ICOS LYZ IFI30 LRRK2 TNFRSF1B ELL2 PLEK BTK EVI2B GZMK BCL2A1 CD69 C1QC TPST2 PLA2G4C HAVCR2 STX11 TLR1 SLC9A9 COP1 CST7 HLA-DQB1 STAP1 MARCO LAPTM5 TLR4 CLEC4A GLRX DOK2 CCL2 SUCNR1 IL18 IL10 CD53 SLCO2B1 FGL2 GZMH FCGR3A P2RY10 IL7 MEF2C LAG3 PTPRC IL2RB CASP1 RNASE6 ZEB2 KCNMB1 CD72 KLHL6 RHBDL2 CYBB GPR18 MS4A4A HLA-DPA1 RGS1 GPR34 HLA-DQA2 ASAHL C2 LAIR1 FCER1G SLAMF1 DPYD GBP2 SIGLEC1 PKD2L1 CD3D STOM AIF1 LAT2 LILRB1 CXCL9 GIMAP7 IL21R HLA-DOA TMEM176B CXCL10 SLA FCGR2B KLRB1 DOCK2 MS4A7 CD52 EBI3 PLEKHQ1 IRAK3 ABI3 LST1 LY86 TREM2 HCLS1 PIK3AP1 CXCL13 IGSF21 PYCARD TAGAP EVI2A FASLG SLC31A2 RAC2 GNLY LGALS9 NAPSA SERPINB8 CD48 CTSS SIGLEC7 ARHGEF6 DRAM HMHA1 HCST APOBEC3H VAV1 ITGB2 CCL5 SIRPG LPXN DOCK8 HMOX1 DAPP1 CCDC109B SERPINB1 FYB URP2 MSR1 ITGAM EPB41L3 IFNG TMEM156 RAB27A C1S MNDA WDFY4 NLRP3 SLAMF7 ITGA4 OSM ITGAL FTHP1 PGDS HCK IRF8 ANKRD22 PTAFR GZMB KLRC1 TRAT1 FCN1 JAK2 NCF2 CD14 IL18RAP STAT4 VAMP5 ARHGAP18 IFNGR1 HNMT TREM1 ARHGAP9 GPR84 TBX21 CCL4 CLEC2B CIITA STK17B BIRC3 FOLR2 TNFSF13B ARHGAP15 NPL GIMAP8 CCL23 NNMT C1QA HLA-DMB OSMR CCR5 TRAF3IP3 SELPLG EDG6 HLA-DRA HTRA4 P2RY14 MAN1A1 TMEM71 TNFAIP8L2 CENTA2 ZNF683 CATSPER1 MLKL NOD2 CXCR6 TNIP3 CORO1A GMFG GIMAP5 PTPN22 WIPF1 AIM2 PYHIN1 SMPDL3A NR3C1 MDFIC LILRB3 SRGN FPR1 RHOH GPNMB CLECL1 TNFSF10 CYB5R4 CD5 GIMAP4 NCKAP1L RCSD1 INCA RNASE2 SOD2 OSTF1 MMP9 P2RY5 GIMAP1 SAMD3 HLA-DPB1 TBXAS1 HLA-DMA SLC37A2 UBD APOBEC3G FBP1 MS4A6A EBI2 OLR1 VNN2 STAB1 IL1B SIT1 CCL13 TNFRSF14 TLR2 FPRL2 C1QB CLEC5A CRTAM IKZF1 PLAUR SDS FAS GPR65 SPI1 MPEG1 CD180 APOB48R SPP1 CCL8 UBASH3A SNX10 RGS18 TLR7 TLR8 ATP8B4 CCR7 BATF LRRC8C CD38 HPSE NLRC4 FCGR2A IGSF6 B2M GIMAP2 LACTB PDE4B PRDM1 SH2D1B PSCD4 TLR6 BIN2 CLEC7A CCR1 SLC7A7 CD27 OGFRL1 TMEM176A TFEC ARHGAP30 GPR171 LILRA4 ALOX5 SH2D1A ARL11 CD28 LTB CD37 AMICA1 CXCR3 APOC1 SIGLEC5 TIMD4 KLHDC7B PYDC1 TNFSF12 CD300LF NKG7 NCF4 TGFBI ITK PIK3CG EOMES PARVG F13A1 CD68 DOK3 TRPV2 CCR2 CD86 DPEP2 APOL1 P2RY6 IL13RA1 ARHGDIB ALOX5AP GAB3 CD74 CASP5 ADAM8 NYD-SP21 SECTM1 CARD6 C3AR1 PSCDBP VSTM3 FLI1 MFSD1 CFD SIGLEC10 P2RY13 IL2RG NCF1 SLAMF8 IL7R SQRDL ADAMDEC1 CD163 DAB2 TNFRSF9 CD3G SAMSN1 CD84 CLEC4E IL2RA IL15 RASGRP3 DNAJC5B FPRL1 MMP25 APBB1IP FCGR1A LILRB2 GNGT2 CLIC2 HLA-DRB5 CD96 MGAT4A ACSL1 LRRC25 GIMAP6 CD247 LILRA2 ADORA3 TMEM154 PTGDR VMO1 LILRA3 CD2 ECGF1 LY96 LYZ CCL3 CLEC10A GNB4 CSF1R RP5-821D11-2

22 S.Table 3(Cont’d) Module 1b…..(Cont’d) CCL17 GPR92 KLRC2 PLEK2 SERPINA1 KBTBD8 MT1B DERL3 MT1H CMKLR1 THBD CHST11 SAR1B MVP TNFRSF17 CEBPD IL22RA2 EAF2 SPPL2A CCL18 SERPINB9 ITGAV TRPM2 GPR155 CDKN2B HAPLN3 MAFF HLA-DQA1 SFT2D2 VDR S100A8 ABCC3 NFKBIE SPCS3 ADAM9 BIC PSTPIP2 CDCP1 SELP IL32 CTSC EPAS1 TFEB TLR5 FCRL5 SLC46A3 UPP1 PLEKHF2 CXCL1 CD302 RNF152 PLK3 FTL STK3 CCL19 CTSL1 STX7 CASP4 PTGER4 VNN3 AHR ADCY4 AADACL1 APOL2 RARRES1 SGMS2 ARL6IP5 NINJ1 MAP3K5 S100A11 XBP1 PADI2 P2RY12 TMEM87B SGPP1 ACP5 RELB USP12 TMOD3 S100A16 TYROBP PKIB FTH1 TEX11 CLEC12A MUC1 QPCT ELF3 TMSL3 HPR YWHAH ICAM1 PTPRE ABHD3 TAPBPL KCTD12 FRMD4B FKBP5 AYTL1 PVRIG PTGER2 MAFB MOBKL2C BCL3 SYNGR2 RNASE1 TMBIM1 LCK HVCN1 APOE CLEC9A BLNK A2M CD1C PPARG RRM2B PMAIP1 KLRC3 GBP3 CD6 TCIRG1 CASP7 NRP2 DBI HBEGF GNG12 IL1RN HSPA6 SLC28A3 VSIG4 EMB RASSF5 MT1JP IL12A IRF4 IL4R BST1 LCN2 MFSD7 PIK3IP1 SGMS1 CHRNA6 MT1X KLF9 KYNU FCER1A KLRD1 G0S2 CD59 TRAM1 SLC43A3 IL33 FRK LYSMD2 AMPD3 SNFT ZNRF2 ABCA1 NDRG1 CXCL6 BTLA MT1M LCP1 RIPK3 RNF213 GGTA1 PQLC3 NTN4 CP CTA-246H3-1 IKBKE LXN CTSH UNQ473 SPECC1 COQ2 SLC25A43 JAZF1 RAB20 RAB27B MR1 FBXO32 RAB32 CARD9 ADAM10 VTCN1 KLHL5 OBFC2A IRAK4 ITGB6 CCL7 FBXO6 RETN SLC16A3 TRPS1 CSF2 BID ARRDC2 NCR1 IGKC PBEF1 HERPUD1 AP1S2 SLC41A2 ATP6V1C1 PRKCB1 SLC19A3 CD58 CBR3 CCR6 TMEM165 TMEM49 ANXA1 TNFAIP2 ITM2A CAV2 ST8SIA4 CACNA2D4 CXCL16 RFTN1 HTR2B CFP MAG1 TXNDC3 INDOL1 IGKV1-5 ARRB1 INPP4B NCK1 NUPR1 LMO2 LY75 LGALS12 SLC1A3 FLVCR2 DSE LRMP LAX1 HAMP ZMYND15 KRT23 ARNTL PCDH7 CD44 TNFRSF4 NCOA7 IL4I1 TTC9 CD55 TMEM149 IFNAR2 CBR1 MLZE PSTPIP1 HS3ST1 TMEM173 DARC MT2A GJA5 ALPK1 PLCL2 MRO DENND3 CFH CYSLTR1 S100A12 SGK SLC39A8 VAV3 HS3ST3A1 PAG1 CFB CFHR3 SLC35D1 CTSB CTSZ PDZK1IP1 PGCP CD40 FTHL17 ADRB2 DUSP10 GPX3 SKAP2 AQP9 S100A3 FMO3 CD47 LAIR2 FMO2 MMAA LRG1 RAB9A SOAT1 NFATC1 IBSP TSPAN12 C3 DHRS9 GFI1 TNF HTR3A CSTA HPS3 SCIN CEBPE PCAF LGALS2 ACSL5 CD274 MMP12 PLAC8 TSPO SUSD1 IL8 RASSF4 PDCD1 KCNK13 HHEX TC2N SAMD8 RPGRIP1 NFKBIA IRF5 CPA3 S100A6 GYG1 PTPLAD2 RCAN1 HOXB4 EIF4E3 B3GNT3 CSTB TNFAIP8 OPTN CLEC4D MAF GRAMD3 RNF19A LGALS3 B3GALT4 GPR137B SAA2 RILP TMEM59 JAKMIP1 ATP8B1 XCL2 PLA2G7 LITAF RBM18 IGHM RIPK2 APOL4 NPAL2 ARPC1B VCPIP1 EGR2 CASP10 TBC1D10C S100A9 PRKCH MAN2A1 CLC HGF UBE2J1 TM4SF1 RNF175 NFKBIZ SAA1 TNFAIP3 TPSAB1 DERL1 CX3CR1 BTC STEAP1 SLC25A46 RRAS SAT1 VNN1 APOC2 RNF19B ERO1L LNPEP PLXNC1 GCH1 GMPPB

23 S.Table 3(Cont’d) Module 1b…..(Cont’d) Module 2 - 631 genes POU2F3 RTN2 APOBEC3F PSCD1 TIMP1 CAPZA2 CAPZA2 HSPA8 FCRL2 CXCL2 SLC5A1 SLC38A6 SRD5A1 RBM7 RBM7 IMPA1 hCG_17573 hCG_17573 PPM2C BLVRB ACPP SDC4 KRT81 35 35 NXT2 ZC3H12A LYST TINAGL1 EMILIN2 STXBP5 SCOC SCOC UBTD2 tcag7-1314 AIM1 DDIT4L CADPS2 DEFA3 SLC35A5 SLC35A5 KIF2A SRD5A2L COBLL1 XCL1 CCDC47 DHRS3 HIAT1 HIAT1 UHMK1 PDE4DIP SELM MYH9 PLEKHF1 PRKCI LYPLA1 LYPLA1 SYPL1 ABCG1 CYBA ATP6V0D2 DENND1C FCGBP VPS26A VPS26A NCOA4 KLK7 POU2AF1 PXK TCN2 ENTHD1 PRDX3 PRDX3 AKTIP CKLF ST3GAL1 CYP4V2 AGA PI3 MINPP1 MINPP1 UBXD4 GPR115 CAPG PCTP ANPEP PTER TMED2 TMED2 CDC73 SEC14L2 UGCG TFRC PF4 PBX3 MORF4 MORF4 ACADM TNFRSF10A CAST FKBP11 SLC8A1 ARID5A PSMD10 PSMD10 SELT MMP7 TNFRSF21 RBM3 ZBTB16 RNF148 COPS4 COPS4 TXNDC12 DOCK4 RAB42 SERTAD1 TACC1 IGLL1 SRP9 SRP9 DENR PRKAA1 RFK S100A5 ZNF671 IGLV2-14 DR1 DR1 RNF138 VPS13C ZNF217 CCL20 CRYAB RRAD SMAD4 SMAD4 YIPF5 BANK1 CHIT1 VGLL1 ZHX1 PTPRO CAND1 CAND1 DNAJB4 ASL PIM2 XDH PDE1A SH3BGRL IFT52 IFT52 LIN7C NRP1 IL6 SLN ST3GAL6 OAT SNX6 SNX6 CDC42SE2 ARTS-1 MMD STEAP2 STEAP4 IL12RB2 TXNDC9 TXNDC9 STX12 PLB1 CD1A RNF217 NINJ2 CASC4 RAB28 RAB28 CCNC HRH1 MICALL2 SOCS3 CXCL5 MS4A1 HBP1 HBP1 THEX1 SLFN5 ZFP36 RASGRP1 IL19 SIDT1 METTL2A METTL2A RQCD1 AMPD1 BBOX1 S100B ARSA RASGRP2 UNC50 UNC50 GNG10 SLC39A11 GABRE KLF6 TBC1D8 CD70 RSBN1 RSBN1 PGM2 SC4MOL SREBF1 DOCK10 BTBD14A FLT3 RCHY1 RCHY1 DHX40 PDZD2 EFNA1 CX3CL1 CD79B ZNF215 NMD3 NMD3 CCDC121 NCALD LRP8 GFOD1 LACTB2 ASPHD2 BRMS1L BRMS1L INSIG2 GABRP SLC22A4 CHODL GPR109B FCRLA MORF4L1 MORF4L1 PIGF BHLHB2 RASGEF1A SLFN11 KLK10 BCL11B VBP1 VBP1 RAP1A RUNX3 IL6ST ADRBK2 SNX7 UBE2Q2 UBE2Q2 RP11-114G1-1 FGD5 NEK6 TIMP4 TIGD2 UBE1C UBE1C B3GNT2 TPK1 CCBP2 BIK DIO3 ZNF267 ZNF267 TMEM66 MATK LIMK2 CA2 LOXL4 SERP1 SERP1 ATPBD1C TBC1D2 CPNE8 IL6R LEPROT CHUK CHUK ZFAND6 TFPI2 MTP18 AXL NAIP VTA1 VTA1 PAQR3 CDC27 CHMP5 SLCO2A1 SSR1 TSNAX TSNAX PRMT3 ACSL4 MALL USP25 NTNG2 SNAP23 SNAP23 SIAH1 LAPTM4B IL20RA SLC10A3 RGL1 GMCL1 GMCL1 ZNF140 SCARB2 HSCB STARD4 REEP3 GSPT1 GSPT1 SLC35B3 MAML2 ETHE1 SH3TC1 ANKH TMEM30A TMEM30A DCK GNA15 LMNA ME1 SGPL1 YTHDF3 YTHDF3 MAT2B

24 S.Table 3(Cont’d) Module 2 …..(Cont’d) NOL11 SESN1 PI4K2B MRFAP1 CHAC2 RPL21 SENP6 PGGT1B MTMR6 MFSD8 KBTBD3 FPGT DCTN3 CD9 ACN9 PANK3 TUBE1 SLC25A24 CCNG2 MOBKL1B CCDC111 SLFN12 P4HA1 MANSC1 NDFIP2 TXNRD1 XRCC4 EHHADH TGS1 MTFMT HINT3 PDSS2 CEPT1 MYCBP MRPS23 PPT1 GNPDA2 ENPP4 LYRM1 RP11-11C5-2 TMED5 MKRN2 RANBP6 RDX TANK HADH CCDC98 CROT CRBN DNAJB9 TBC1D9 B3GALNT1 GINS3 RTN4 SC5DL GUCY1B3 KPNA5 XTP3TPA SNAPC3 E2F5 CCNG1 BMI1 MAGEH1 SOCS6 MANEA DYNC2LI1 TMEM9B UBE2E2 ZNF420 PLS1 PEX7 SLC39A10 ZNF670 MAPK9 TM2D3 PHOSPHO2 BMPR1A FIG4 POLE3 PHF10 HDX YEATS4 LIG4 HSF2 DNAJA2 PXMP2 ALG5 ELF1 SLC30A9 CYB5B LRRC42 ITFG1 ARL6 NPTN PLEKHC1 COQ3 TTRAP SNX17 DCTN5 PRKAR1A STRAP USP46 AP1S3 TMEM128 NR1D2 PPP2CA COMMD2 CUTC SERAC1 CXADR CG018 SERPINI1 NANP SUCLG2 DC2 TMEM70 STCH UBE2E3 TAF1A NUDT12 ALG10 CGRRF1 CCBL2 DRG1 TSPAN6 EID3 DHRS7 PYROXD1 PANK1 FBXO22 WDR51B LMBRD1 BCKDHB CRYZ ETFA DHRS12 SLC25A4 UBE2NL ETNK1 MLSTD2 APIP 0 RRAGB ACAT1 RWDD2A MOSPD2 SEPSECS DUS4L TMEM64 TCEAL8 NNT IMPAD1 CLN5 FBXO3 TXNDC1 COMMD8 RAB23 RAB21 RP11-151A6-2 PIK3CB CCDC34 VPS4B FEM1C THAP9 PJA1 SFXN1 TMEM14A IMPACT NEK1 TMEM182 PDCD10 GABPA SPRED1 RNF111 SGCB ZNF277P TMEM32 TCEAL1 WDSUB1 TRIM23 GTF2H3 CCDC138 USP1 ERMAP NUS1 MTERF COMMD10 PIGH TMEM68 TM7SF3 CKAP2 ARHGAP5 ATG5 PAIP2 TM2D1 ATP5B ASAH1 ZNF595 C1GALT1C1 CNIH FZD6 GOLGA7 CTSO PXMP3 SIP1 PPP1CB MUTED PRKRIR CEP170L LIPA RFXAP C1D TWSG1 TMED7 bA16L21-2-1 MPHOSPH9 UQCRFS1 SVIP HIGD1A ZFP37 NIPSNAP3A SLC30A1 STYX TPMT HSDL1 ZNF684 FBXL3 RWDD4A SLC35F5 EEF1A1 GALC TFDP3 IQCC TMEM50B MBIP P15RS METTL9 ZNF641 ACVR2A FGFR1OP2 MTM1 ADH5 ZFAND1 PEX3 SLC25A5 KPNA3 PGRMC1 SMURF2 ITGB1 SCAMP1 PRIM2 YAF2 TTC5 TRDMT1 THAP10 IFT88 NUDT15 FBXO4 SUCLA2 ZNF294 TASP1 NDUFB5 TMEM14B TIA1 DEPDC4 ATP6AP2 ARL6IP6 ARSK OSGEPL1 BBS12 SLC39A6 ZNF572 BTBD3 RAB1B IDI1 GOLT1B CRADD CCNDBP1 TRAPPC3 NUDCD2 TMEM38B CCDC126 MAP2K1IP1 SOCS5 ARL5B CANX RECQL MED30 TEAD2 NSL1 WDR57 FECH VAMP4 SEPP1 NDUFA9 SUMO3 HDDC2 GNA13 PSAP FUNDC2 TBPL1 PFN2 COG6 TMCO3 RCN2 NIPSNAP3B CYP39A1 CRY1 NME7 AK3 RP11-217H1-1 TOM1L1 NMT2 UBE2W TTC30A NPAT WDR5B TM2D2 GPR180 L2HGDH RFC3 DPM1 ZBTB26 MYNN MTFR1 TTC30B TMEM17 OCLN AKAP7 DUSP11 ZDHHC13 PPP2R2A NDUFA10 ALG11 PCCB MOAP1 B4GALT6 ZBTB6 TM9SF2 MIPEP TRAM1L1 TMEM144 SENP8 STARD3NL MTRR

25 S.Table 3(Cont’d) Module 2…..(Cont’d) Module 3 - 631 genes MED21 ELOVL5 TMEM19 AUH PTPN14 COL5A2 POSTN HEPH LAMA4 CEP70 ATE1 ARMCX1 hCG_2004593 PPP1R13L SPARC ECM2 PLXDC1 GJB2 ZNF570 DSG2 NGFRAP1 YPEL1 PRKCD COL5A1 ETV1 KCNE4 CALD1 ENPP5 DTWD2 CCT6B GALNT4 TRMT1 MMP2 ANTXR1 FSTL1 SLAMF9 TMEM20 ATAD1 RMND5A ACADSB GPRIN1 AEBP1 CCDC80 COL6A1 HEG1 ASNA1 ITGAE MCCC2 TFDP2 DHCR7 LUM ACTA2 PALLD EDIL3 PITPNA THAP2 ALDH3A2 HSP90AB3P RTEL1 THBS2 ANTXR2 SFRP4 PDGFRA AQP11 UHRF2 CHPT1 PAQR8 SHROOM1 VCAN P4HA3 ITGA1 NKX3-2 SLC22A18A ANKMY2 GPRASP2 GPR160 ANKRD46 S SNAI2 PDPN LPPR4 ENOX1 TSPYL4 TRMT11 SUGT1L1 NEURL2 JUND COL1A2 MSRB3 PLAU TNFAIP6 DPY19L4 RNASE4 SRR ASB9 IER5L INHBA OLFML2B HAND2 LOX CASP6 BAG2 ZSWIM7 CACNB3 HSPB1 FBN1 PODN GALNT5 NID2 CTNNAL1 GLRB EID2B RNF165 PLEKHN1 FN1 SFRP2 IGFL2 ZEB1 PON2 RBBP7 BEX4 ALDOC RHBDD3 COL1A1 DACT1 DACT3 TCEAL7 ARAF RPS3A NARS2 SEMA3B TRIM74 ITGA11 TIMP3 CD248 MMP13 PPP2CB MCOLN3 HSPC105 VASN WDR91 COL6A3 LOXL2 AK5 CCL11 ADFP MRPS6 RBM11 PEX6 ABCA3 FAP ACTG2 LOXL1 COL5A3 PRPS2 TAF5L SEC11C CLDN3 LAMB2 WISP1 PMP22 COLEC12 GREM2 THNSL1 UBE2E1 EID2 SCRN1 HIPK2 DCN ANGPTL2 ASAM SEMA3D LRIG3 IMMP2L MIPOL1 ZDHHC14 BRD4 CRISPLD2 BGN COL16A1 AOC3 IDH3A NUDT4 PLA2G4A CXXC5 ZFHX3 COL6A2 LRRC15 RUNX2 SPHK1 NRAS TMLHE HACE1 DDEFL1 SRGAP1 GLT8D2 ECM1 FGF7 VCAM1 CPD MTHFD2L MED28 TLN2 TMC6 COL11A1 OMD TMEM46 ALDH1A3 MOSPD1 ZNF626 PIGN EPS8L2 BCORL1 PDGFRB FZD1 C1QTNF6 FMO1 RAD9B ZNF124 FDFT1 ALDH16A1 PURA CDH11 EPYC HTRA3 RANBP3L ABCC4 TSC22D1 DERA CDC42BPA MTF1 CTSK NUAK1 CXCL12 PTRF ZNF452 PIN4 RAD18 MYO9A ZBTB43 SERPINF1 PPEF1 KIF26B AQP1 SGCE BNIP3 PIK3R1 N4BP3 HCN3 ADAM12 ITGBL1 GPR124 COL6A6 CDCA7L GLCE PPIL3 STMN3 PHACTR4 COPZ2 SVEP1 NEXN FABP4 ECHDC1 HDGFRP3 DEGS1 CKMT1A FILIP1L GREM1 ALPK2 COL4A1 DGKE MED31 QRSL1 NRN1L PDLIM3 COL10A1 RCN3 MSC LTB4DH ARHGEF3 PAK1 MAN2A2 COL3A1 MMP11 TGFB1I1 MMP14 CYB5A ACAA2 UBXD6 CCDC130 PRRX1 CTHRC1 LAMB1 TMEPAI GNB5 DNAJC18 MEGF9 LRRC45 HNT SPON2 DPT LZTS1 PARP11 NRIP1 REV3L SDC3 CHSY-2 EDNRA RGS4 MOXD1 STK38L TMEM18 RAB7L1 ZC3H7B THBS1 FRMD6 MMP19 SCRG1 SLC25A4 CMTM6 MFAP3L WWC3 ASPN SRPX SCG2 NBLA00301 SSX2IP ASB7 BAG4 ZNF652 LHFP BHLHB5 TMEM158 ASPA KBTBD7 USP45 RNF145 PCSK4 COL8A1 PTGIS CXCL14 DCHS1 TNPO3 AMN1 CDKN1B IFT172 ADAMTS12 PCOLCE GEM TAGLN CMAS MYO6 GSTO2 UAP1L1 ZNF469 RAB31 PLN CALB2 SLC40A1 HSD17B11 STX18 HIVEP2 AGTR1 SRPX2 ZCCHC5 CORIN TMEM163 TSPAN13 MREG ITPR3 FGF1 GFPT2 MST150 FNDC1

26 S.Table 3(Cont’d) Module 3 - 631 genes ABCA6 GRP SGIP1 ARHGAP28 PTPRD ARSJ TRPC6 SLC2A3 OLFML3 ADH1B NAV3 SH3PXD2A GNG11 CYP1B1 LGI2 MGP LDB2 CNN1 JAM2 MFAP4 TMEM45A ENPEP ATP10A GJA7 MATN3 RASGRF2 ELN CYP26A1 SDC2 TMEM133 NAV1 THY1 COL15A1 NBL1 ADRA2A FKBP14 ODZ3 FBXL7 NR4A3 OSBPL5 GALNAC4S- IGFBP4 VIM SMOC2 ST6GAL2 6ST PLA2G5 DUSP1 P4HA2 COL8A2 SORCS2 RAI14 ENPP1 GAS1 PITX2 LRP12 TUBB2A GUCY1A3 TNFSF4 LATS2 PRICKLE1 PCDH18 SH3D19 ITGB5 FGD6 F2R SULF1 CLEC1B HHIP ZMAT3 MME PXDNL CDC42EP3 CTGF DDR2 NEDD4 IGF1 MYH11 IGFBP6 GPC6 LSAMP C1QTNF3 RGS17 COL12A1 SPOCK1 CHN1 S100A10 EPHB2 CYP26B1 RGS16 CDR1 LEPRE1 GJA1 PCDH17 SORBS1 SEMA5A EFEMP2 GPR1 HSPB7 FBLN2 OGN SGCD APOD AMIGO2 PRICKLE2 TWIST1 MARVELD1 PCSK5 KDELC1 NCAM2 EBF1 KCNJ8 CDKN1A HTRA1 JAM3 RGS2 PXDN SPSB1 UNC5B PDGFRL PRPH2 ZFHX4 CCDC102B PLK2 KDELR3 SLITRK4 TNAP ABCC9 LRRC32 DIO2 TDO2 DOK6 IGFBP7 EMP1 STX2 PODNL1 BDKRB1 LMOD1 TGFB3 CYP7B1 MYLK MRAP MRAS PRR16 MMP1 SERPINE1 PDGFD ADAMTSL3 LIMA1 BMP2 CLIC4 WNT4 HSPA12B PTGER3 SEMA3C ISL1 SEC24D SLC16A7 PROCR DPP4 RND3 MRVI1 CCL26 MEOX2 SDC1 ANXA2 IL18R1 FZD7 DST CCRL1 PLS3 TLL1 LTBP2 HAS2 GLI3 APBB2 ANGPTL1 CH25H SLC12A8 RUNX1 MAGEL2 FHOD3 DENND2A ADRA1B DLX5 HMCN1 FSTL3 CMAH ABCA8 CPZ KCNJ15 MMP3 TRPC3 RUNX1T1 PAPSS2 GHR COL4A2 TUBB6 CNTN4 MAMDC2 LIPG DKK2 DLC1 SEMA7A SPOCD1 TIMP2 KLF10 NOX4 LEP TNN SYTL2 ARHGAP24 TMEM2 SUSD5 PDGFC SV2B EPHA2 SULF2 BCHE MARCKS ST8SIA1 TBC1D8B SLIT2 CHSY1 VSNL1 PHLDB2 FLRT2 EFEMP1 LEPREL2 FAT BDKRB2 BACH2 EXTL1 NT5E C1QTNF2 CILP LRRC17 RCAN2 CLSTN2 TNC OSBPL6 PLAC9 BMP4 MXRA5 RHOBTB3 TPM1 FLT1 SNED1 ENTPD7 GGTLA1 SCT SELE GDF6 AMZ1 SCUBE2 PPAPDC1A DIP2C CYR61 PLVAP ADH1A FOXF1 NDN EDG2 SLC22A3 AMOTL1 C1QTNF5 LGALS1 FKBP7 DPYSL3 DCBLD1 LPL DOCK11 IGFBP3 CBLN4 BASP1 TPM2 RGS5 MYO1B FNDC4 RHOJ BNC1 TSHZ3 GPR23 SNAI1 ADH1C RARRES2 SIPA1L2 CAV1 GOLIM4 HOM-TES-103 ACAN TCF4 MS4A2 RBMS3 PLIN GRID1 VEGFC DEPDC7 MXRA8 ADIPOQ GADD45B PSCD3 CUGBP2 LRRC4C FOXF2 COMP CNN2 CIDEA ZNF365 ANKRD50 PDLIM5 HSPB8 PPFIBP1 CMTM3 PRKCDBP ADAMTS5 ROR2 ZNF521 RNF128 NAP1L3 STMN2 GPR68 PRKD1 EHD2 PTHLH CDH13 PPIC DCLK1 SLC24A3 FIBIN GPR4 PDE10A MFAP5 KAL1 EIF5A2 TGM2 PLOD2 HSD17B6 CD36 AFAP1 APCDD1 SCHIP1 TPBG PALM2-AKAP2 SESTD1

27 S.Table 3(Cont’d) Module 3…..(Cont’d) Module 4 - 515 genes TRPC1 MXRA7 FBLN5 ACF TRPM1 ELA3A POU4F1 RBMY2FP TMEM47 PTPN13 ACCN2 APOA5 CCDC26 PTGFR MYO18B SPINK5L3 BNC2 PRND DAAM2 SULT2A1 FETUB AGXT2L1 ZDHHC22 FGF19 FLNC PPAPDC3 FMN2 MS4A3 CSN1S1 TTR CYP2F1 TAC3 ANGPTL7 PDGFA FREQ PLA2G12B FGL1 HEMGN PAX3 WNT10B HSPB3 FOS UACA PRDM7 NAT8 ISX HYAL1 MYH2 PFTK1 PPP1R3C AHNAK2 NR2E1 AFP CPS1 BLK ACCN3 TNFRSF12A SOX4 HAS1 SERPINA7 FGG NANOGP1 MSMB IGF2BP1 CLIC3 CRYGN MDFI GYPE KLRC4 OR1D2 CLDN14 CCDC141 ERRFI1 KGFLP1 EPHB3 SLC12A3 MYO1A PRSS7 RHOXF2B HSF4 FLNA TPST1 NET1 GYPB KRTAP1-5 NUP210L PUNC DRD5 GLT8D4 DZIP1 GNMT SLC17A2 PAQR9 SYT6 GBX2 WNK4 SHC2 CHRNA3 ECEL1P2 JARID1D RAET1E TMED6 HOTAIR CORO6 SLIT3 SPRY4 TFF2 DDX3Y MYPN KCNK12 TRIM49 MIA2 PHLDA1 PRSS23 WDR77 SLC18A1 TFAP2B C4BPB TMEM145 PRDM13 ROBO2 AMOTL2 MYB TSPY2 TSGA10IP GABRB1 EN1 TDGF1 NUDT10 GPR87 SPDEF PRAMEF8 ANKS4B RAB3B THSD3 UTS2 WNT7A F3 BDH1 FGB SMOC1 FABP1 CTSG PDILT CPXM2 FGF2 SERPINA4 FGF23 IRX2 SPANXD SPRR2D OLFML2A REP15 ONECUT1 ART4 RPS4Y1 GALR1 CACNA1H COL24A1 CLEC2A PIWIL2 IL23R ITIH2 SPINK4 LCTL CHRNA1 KCNK2 MLANA RLBP1 TBX10 PROC GATA3 CCDC88A EDG8 TYR TERT HBQ1 CA5A CHRNA9 LIX1 LIF ADH4 SLC30A10 SERPINA6 NPPB GPR174 ID2 EGR3 NDST4 NR0B2 FTCD SLC35F4 ONECUT2 KHDRBS3 CPE SERPINA11 KRT37 DCX SLC5A11 CRYBA1 TMEM130 PAK3 XKR3 POU3F2 NKX2-2 ALAS2 GCKR PSD3 ANKRD1 ALB BMP5 MAPK12 TDRD1 NETO1 EBF3 ADAMTS9 OR51B5 C8B LIN28 KRT34 SPTA1 PDZRN4 VAV2 CPN1 ABCC2 LTB4R RHEBL1 NOTUM SFRP1 MMP23B ACSM2B FABP7 HGFAC UGT1A6 EPGN DSC3 GAP43 MRGPRX3 HBG2 ZIC3 PRODH DQX1 ENC1 TRPA1 CGA SLC7A14 SERPINA10 CHST8 PLAC2 ARSE DMN SLC2A2 CDH9 NR1H4 RHD EEF1A2 HAPLN1 KRT80 LCT CEACAM5 HAND1 IGFBP1 UMODL1 SVIL OSR2 APOH SLC6A4 NEFL L1TD1 CALCR PROS1 TSKU ESX1 CREG2 SCGN ST8SIA3 DSCR4 MEG3 AKT3 SLC45A2 GLRA3 ADAM2 CSMD1 CES1 FOSB AKAP12 KLB KRTAP3-1 HPD F5 PNLIPRP2 EPDR1 GUCY1A2 CLCA2 SMCR5 HOXD13 GDF3 SLC7A3 DGKI COL21A1 TMEM83 VIL1 SERPINC1 DLX2 CPB2 ID1 TIAM2 MBL2 GATA2 NEFM GYPA HSD17B2 ZFPM2 ACTA1 RPS4Y2 C8A PTPRZ1 LBX2 NLGN4Y

28 S.Table 3(Cont’d) Module 4 - 515 genes IGSF1 CLTCL1 CD8B TCL1B GALNT3 EMX2 BOC HOXC13 HOXB13 RAB3C PLA2G2A HSD17B14 XPR1 WNT2 DPPA4 TMEM59L RHOV SERPINB4 ARL13B AQP5 DSC2 FBXL21 TUBAL3 UNC5D SATB2 RP4-747L4-3 ISLR ZMYND12 ROPN1 MAGEB2 UGT2B4 MGAT4C OSBPL10 CNTN3 ZNF396 NLRP11 ZNF488 CYP24A1 PGLYRP4 SYK BCL2L10 CD93 HOXC10 MNX1 RGS20 ELMOD1 KRT4 MDS1 MYL9 MAGEA8 OTX1 SALL3 FOXG1 GJB6 GPRC5B UPK1B SOAT2 ULBP2 SAGE1 GDA MFSD4 LYVE1 TM4SF18 ARG1 ANGPTL5 CBLN1 TSLP PDE6B KLK5 FCN3 PCSK9 FUT5 CDH10 RNF186 SLC7A4 TMCC3 CLDN16 KCNG3 PAH UGT2B15 PRDM14 KLHDC6 PBX1 SCN2B BTBD16 GFRA1 CYP27B1 SLCO4A1 ZNF454 EDG7 ANKRD6 CPA4 UNC13A MAGEC1 SLC6A14 EDAR FMOD KCNJ2 TSPAN18 ELOVL2 SULT2B1 PCSK1 MYRIP TMIE BMPR1B CPNE7 ORM2 PTPRH PAX6 CSRP1 OXGR1 C1QTNF7 AURKC CYP19A1 SP8 HOXA13 IHPK3 OXR1 PLEKHG1 ABCG5 MYL7 BEGAIN DMBX1 OVOL2 PAX8 RIN2 ODZ1 EGF IL1RAPL1 HOXB9 NUAK2 NUDT16P EGFLAM ZNF659 IL11 ITIH3 KRT27 EFNB2 IL1RAP MMRN2 AGT BCAS1 P2RX5 SLC47A1 CYP26C1 TRPV6 CRB2 PLP1 SSX5 SEZ6L MPV17L RP13-347D8-3 NTRK2 MEIS1 ODAM SPRR3 GGT1 ALX1 EMX2OS HEYL OR7C2 SOX21 PRAMEF2 NKX2-5 SH3TC2 KLF5 ARPM1 RALB PRDM12 POU5F1P3 TRIB3 RORB DNM3 ZNF287 PLXDC2 SLC2A6 CCDC83 ROPN1B INSL4 SESN3 STON2 GJA4 GJE1 PRAP1 DNASE1L2 ALDH1A2 FGFR2 MAP2K7 IRF6 OLIG1 ABCA12 MKRN3 SLC26A4 TMTC2 KCNJ5 SGPP2 GAGE1 SLCO1B1 DKK1 CA4 SYT11 ENTPD3 KCND2 PLAC4 ORM1 RASGRF1 NXPH1 ZNF486 LGR6 CD34 LHFPL4 HOXD11 SERPINB3 AGMAT CHL1 SCGB1D2 RASGEF1B FZD9 CNTNAP3 SSTR1 PAGE1 KLHL24 ZNF501 HOPX NS3BP CITED1 SEMG1 PAX9 ANKRD43 MMRN1 COX7A1 DBH IGFBPL1 AZGP1 SST PSMAL LRRTM1 ZNF366 CDH4 MAGEB6 DNER SLC27A6 EML5 PARD3B SPARCL1 MAGEC2 SPRR1B NKD1 SMPDL3B FOLH1 CALCRL SLC34A2 SUHW1 TMEM171 POU5F1 CCDC85A EDG1 RAI2 ELTD1 F2RL2 PROX1 ATP8B3 SFTPD NR3C2 NMNAT3 CLIC5 EMR1 ART3 CARD11 KLF8 CHST1 PRELP EGFL6 GABRA2 ARID3A SRY WT1 PRIMA1 CBLC EHF SLC38A5 DSG3 TYRP1 EXPH5 ITIH5 EMCN HIGD1B PTHR1 MYOM3 PI16 CYP4Z1 MYOZ1 JRKL CLEC14A C8G CCDC116 AMDHD1 GPRIN2 KCNE3 RFTN2

29 S.Table 3(Cont’d) Module 5 - 315 genes CENPA NEK2 CDC7 CKS2 CABYR MRPS12 GALNTL4 TMEM139 TOP2A CDC25C CENPL CENPH FANCA SLC36A4 WWC1 CLIP4 KIF4A CKAP2L GINS2 NCAPG2 THOC4 PSMC4 MLPH RHBDF1 NUF2 OIP5 ESCO2 TCF19 NCAPD2 CEBPG LCN12 RIN1 KIF15 CDCA3 RAD51 MKI67 CTPS TMEM56 LY6G6C MSLN MELK ECT2 FOXM1 PRIM1 NMU SLC22A16 RBKS TXNIP MCM10 CDKN3 SMC2 EZH2 WHSC1 SMC1A SORL1 PPL CCNB2 KIFC1 RFC4 SHCBP1 OCC-1 PDCD5 SLC22A5 GALNT9 DLG7 KPNA2 TRIP13 HELLS RDM1 PLA2G3 ZCWPW1 ALS2CL NCAPH STMN1 MAD2L1 CIT DMC1 MAP7D2 FBXL14 CLU TTK DEPDC1B CKS1B MCM4 SLC16A10 APOO COL4A3BP MMP28 ERCC6L GSG2 CENPK CLSPN TMEM118 SLC16A14 ITGA2 ITGB4 RACGAP1 ORC1L MASTL LBR CDC25B PDK3 FBXL16 TPX2 CDC45L POLQ MCM8 SASS6 FGFR1OP GRAMD2 CDC2 STIL MLF1IP KNTC1 SLBP RAD54B DOK7 KIF23 PTTG3 BLM RPL39L DDX39 SPINT2 RORC BUB1 CDC20 WDHD1 CDCA4 EP400NL CCNYL1 SLC4A11 UBE2C ARHGAP11A PLEKHK1 CHAF1B ZNF682 TMEM106C ESRRG CCNA2 ANLN ORC6L CCNE1 MTBP CTSL2 RAB17 UBE2T KIF20A CDCA7 DNMT3B WDR67 CDKN2D GRAMD1C BIRC5 PTTG2 TK1 BRCA2 PRTFDC1 ZIC4 DPP6 CDCA8 MND1 TIMELESS GPR19 HN1 TXNDC16 MXI1 NDC80 CEP55 E2F1 PSIP1 IMPA2 SGEF ACOX2 KIF2C RACGAP1P CCNE2 WDR76 TTLL7 ZYG11A RASAL1 CDCA5 PTTG1 PLK4 ZNF695 TMEM48 ZIC1 ZFYVE28 AURKA CHEK1 DIAPH3 RNASEH2A RNF182 ACTN2 XKR4 EXO1 SGOL2 ASF1B CCDC18 LRP2 DMRT3 TRIM8 CENPE FANCI XRCC2 DNMT1 UCHL1 FADS1 RSPO1 CCNB1 RAD51AP1 SGOL1 CENPQ CSRP2 YBX1 NFIX DEPDC1 CENPF GINS1 MAD2L2 NRM EIF4EBP1 EPB41L1 NUSAP1 RAD54L TMPO LMNB1 CHST9 TMEM74 PEBP4 MYBL2 PBK POLE2 CDK2 SENP5 AKR1CL2 GLTSCR2 SPC25 HMGB2 E2F7 DSCR6 BRCA1 UGT8 DTX4 CDC6 PRC1 PSRC1 INCENP EYA3 LGALS7 MGLL KIF18A DNA2L ATAD2 HYLS1 GIPC2 ABLIM2 TRIM29 BUB1B GMNN TRMT5 CCDC5 FABP5 PLLP ZBTB20 RRM2 PCNA PPIL5 HMG4L HMGB3 DUSP4 NPDC1 FBXO5 DONSON BRIP1 SAE2 AKR1B1 BHLHB3 SLC26A2 E2F8 TYMS SKP2 RMI1 SLC25A33 SPRY1 KCNK15 NEIL3 GPSM2 HMMR PIGX PDK1 LAMB3 TOMM7 CENPI GTSE1 TACC3 GPR137C TIMM50 MYO5C CCND1 KIF14 SMC4 DCC1 CHRNA5 NETO2 GAS6 EPB41L4A ASPM SPAG5 GGH COCH RAD51C RPL10L CAPN2

30 S.Table 3(Cont’d) Module 6 - 235 genes RSHL3 PIH1D2 SPA17 RGS22 EFCAB2 CALR3 WDR63 SPATS1 WDR69 LRRC51 RP13-401N8-2 B9D1 TEKT1 KIF9 ANKRD45 MEIG1 MLF1 RP1 YSK4 CASC1 DYDC2 RPGR TRIM55 DNAJA4 IQUB LRRIQ1 AK7 CCDC89 SAG CCDC87 ZMYND10 RTDR1 TMEM190 DUSP19 IFT57 GPR162 CCDC135 OSTbeta TEKT3 KLHDC9 PNLDC1 RAGE TTC29 NPHP1 LRRC23 TSGA10 WDR52 PNPLA4 WDR16 ARMC4 LRRC6 LRRC49 TTC12 RLN1 CCDC19 LRRC43 WDR78 TTLL10 MLC1 PLA2G10 EFCAB1 LRP2BP MYCBPAP IQCK SPATA6 MKX WDR38 TPPP3 MAP6 IHH INTU RUNDC3B CCDC65 SPAG17 FOXN4 KLHL32 RFX3 OVGP1 CCDC37 MBD3L1 CCDC67 RFX2 CLUAP1 SLAIN1 SPEF1 LRRC48 TCTN1 SYTL3 SERPINI2 LIAS SPAG8 FHAD1 AGBL2 ATP4B FBXL2 TMCO5 CAPSL KCNE1 FBXO15 CPXCR1 DNAJB13 MAGI2 ROPN1L MORN3 RAB36 DUOX1 INSL5 TMEM16C EFHB WDR49 KIF6 ZNF214 RNF32 TXNDC13 DLEC1 PACRG FOXJ1 NUP62CL ACSBG1 ARMETL1 LRRC50 DCDC5 TCTEX1D1 IQCG CYB5D1 LRRC46 EFHC2 RP4-692D3-1 AGR3 CCDC41 GAS2L2 SPATA4 FANK1 CDH26 CACNG6 TSNAXIP1 ALS2CR12 FSIP1 LCA5 TCP10L DNAH7 DYX1C1 IQCD TRAF3IP1 MPO AKAP14 CCDC40 IQCH SPAG6 FGF14 TMEM146 NME5 MDH1B TIGD4 ZFP2 KIF19 CAPS2 TMEM67 LDLRAD1 CDKL2 SPATA17 DYNLRB2 CCDC78 ANKRD42 IFT74 STOML3 KCNRG TTC21A CCDC17 USP53 CCDC96 NEK11 RIBC2 GJB7 TMEM157 ARMC3 RIBC1 MNS1 BCDO2 GLIPR1L2 CCDC81 VWA3A FBXO36 DNAH3 PART1 TEKT2 EFHC1 CCDC74B MAP9 GDF9 MAK CDC20B WDR66 C6 STOX1 DNAH9 TTC18 CCNO TCP11 CALML4 DNAI2 SRD5A2 STK33 SLC47A2 TMEM27 RSPH1 SPEF2 LRGUK DNALI1 B9D2 NEK10 UBXD3 KBTBD10 CDS1 EML1 PPIL6 EFCAB6 FBXL13 CAPS ABHD6 CCDC11 SPATA18 LRRC34 HSPA4L TEKT4 DNAH10 MS4A8B DNAH11 TTC16 MTL5 RSPH10B ARMC2 SPAG16 CSPP1 FSD1L

31 S.Table 3(Cont’d) Module 7 - 254 genes CAMK2N2 MAP3K10 GADD45GIP1 RAET1G GALNT7 ZNF85 FBXL8 CDC42EP5 MAST1 WISP2 TAF9B HNRPAB IFITM5 SOX3 MRPL41 SCGB1D1 RCN1 ZNF43 GALR3 GPSM3 WASF4 MANEAL ZNF302 ZNF559 EN2 RHBDL1 TMEM102 LDHD TIGD7 MAGEF1 MAFA TEPP ZC3H6 SLC22A18 ARL9 THOC1 OTUD7A FAIM3 TAOK1 MESP1 PHKA1 CCDC46 NLF2 MMP17 SAPS1 CIB2 SMS SKIL GP1BB HSPB9 GCAT PARD6A F2RL1 AFG3L2 SCRT2 GPR78 VWA1 TP53AP1 ZNF596 ARMCX3 UTS2R CEBPA CCDC88B BIN1 KCNMB3 UTX MYOD1 TCEA2 BARX1 BAGE2 ARHGAP29 FYTTD1 EVX1 ITGB1BP3 MAGIX CMBL ZNF177 INTS2 TSPAN10 DES PRRG4 SLURP1 ARMCX2 CTPS2 COX6A2 FCRLB PRR17 GPR146 NFE2L3 ZNF519 GPR153 HRK TRAPPC5 IRX3 L3MBTL3 DNAJA1 BHLHB4 ABHD14A DUSP23 ALS2CR16 GKAP1 PPP4R1 GPR156 PCSK1N CLPB HES4 ARID2 ATP5A1 LCE1D RPLP1 ELMO3 AK3L1 TCEAL3 WEE1 GPR150 NDUFB1 UCN NUDT14 ERMP1 EIF4A2 ATAD3C SNX8 FOXQ1 PITX1 TCEAL6 ZNF75A PHOX2A BAALC GNB1L ARHGAP22 ATP2B1 UTP3 HES7 ANKRD9 CABP7 CKB ABCA11 TAF11 SOX18 NUDT8 ZFP36L2 SCGB3A1 IDH1 SENP7 psiTPTE22 GPR157 ILVBL LMTK3 HMGCS1 CACHD1 FBXL17 AMH hCG_2033311 KRTCAP3 ZNF545 UPF2 ZSCAN10 TMEM184A CLEC11A MOBKL1A FMNL2 CHIC1 NPBWR1 RPS20 OCEL1 SLC24A1 HSPH1 ZNF146 CDH24 RPL39 GAMT TEC PTBP2 TGIF2 CASKIN1 BEST4 TIMM8B RAB3IP ESM1 TAF5 DLGAP3 VASP TMEM8 TMED9 TCEAL5 NFXL1 GRIN2D WFDC2 NENF USP9X ZNF599 SACM1L POU3F3 IRF7 REEP6 PCDHB4 PHTF1 PRPF4B CACNA1E TMC5 IDUA EPB41L4B HIBCH MPHOSPH1 NEUROG3 PRR15 SYTL1 ZNF568 FUS RP11-78J21-1 HCN4 CCDC57 RPS18 CBR4 SMARCA1 CBWD1 FOXB1 NME3 GPR20 MBD5 STK38 PCTK2 AVP LSR LIN7B PER3 MPP6 NEDD1 KISS1R LYNX1 PRSS22 ZNF248 ISOC1 HNRNPA2B1 LCE5A ProSAPiP1 CCDC125 LRRC1 CLK4 GLI4 VPS18 NADSYN1 PPA1 EPB41L5 ZNF579 SLC9A3R2 PHLDA3 CREBZF PGBD1 LCE2D LIME1 ZNF704 ARL6IP2 CHML

32 S.Table 3(Cont’d) Module 8 - 106 genes Module 9 - 124 genes Module 10-41 genes ILDR1 MBTD1 ZMAT1 IFIH1 SLC15A3 HSH2D EXOSC4 SLC35E4 TBC1D3P2 TRIM56 OASL DDX58 UNC93B1 DGAT1 TMEM137 CRIPAK DDX26B ETV7 ISG15 EIF2AK2 TIGD5 PILRB CROCCL1 PDE6A SAMD9L SP110 SAMHD1 BOP1 AHSA2 BDP1 ITGB1BP2 IFIT3 IFIT1 DDO PYCRL GUSBL1 CSAD LEAP2 UBE2L6 HERC5 CYP2J2 FBXL6 CTGLF5 PILRA LYG1 PSMB9 INDO PIGR EEF1D IMAA COL7A1 PLXNB1 OAS1 PARP12 IFITM3 ADCK5 GOLGA8A SFI1 PHACS XAF1 GBP5 TREX1 PPP1R16A BMS1P5 ZNF789 UBQLNL TMEM140 IFI16 BCL2L14 TSTA3 MYO15B CLCN6 RP5-1022P6-2 TAP1 DHX58 IFITM2 ZNF16 MGEA5 BZRAP1 DFNB59 HLA-B TLR3 SLC37A1 RPL8 ATG16L2 ATHL1 COX19 PARP14 IRF1 CHI3L1 MFSD3 MALAT1 TRIM52 KCNJ14 RSAD2 RARRES3 BLVRA CYC1 CATSPER2 STRC NUDT9P1 HLA-C EPSTI1 ANXA10 EEF1DP3 HERC2P2 COL27A1 PTPRG HLA-F STAT1 NQO1 GSDMDC1 SEC31B GGTL3 PDE7A PSMB8 HCP5 LINCR GPAA1 SFRS18 RPA4 ZNF292 CXCL11 SP140 HESX1 ZNF623 TNFRSF25 STARD9 MDM4 HLA-A LAP3 PARP3 OPLAH PRRT2 AVIL CLEC16A OAS2 UBE1L SQSTM1 SLC39A4 AFG3L1 SFRS16 ZBP1 IFI27 STS NRBP2 GOLGA2LY1 MPP3 IFI44L PSMB10 DHCR24 ZNF250 MCM3APAS AMT IFIT2 PSME2 MST1R EIF2C2 HCRP1 PAQR6 HLA-E IL15RA MYBPH ZNF251 L3MBTL SNRPN IFI35 IRF9 TMEFF1 SCRIB CCDC84 MYH3 TRIM22 IFIT5 LAMC1 CHRAC1 POLR3E ZMYM2 NMI IFI6 FIGN NDUFB9 CEMP1 LRP5L GBP4 IFITM1 EFS TOP1MT ANKRD36 PARC SAMD9 ISG20 FZD2 MAF1 SLC25A27 ZDHHC11 HLA-G BTN3A3 FLRT3 COX6C GNRH1 LUC7L LAMP3 APOBEC3A CLDN6 RNF139 RPL23AP13 GSDML OAS3 HLA-DOB MLLT11 RECQL4 STK36 TMEM16H IFI44 TDRD7 MYT1 NAPRT1 CCDC14 ADHFE1 GBP1 BTN3A2 NOG SLC45A4 WDR27 LRRC39 MX1 BST2 KLF12 TRMT12 ITIH4 ANKAR APOL6 BTN3A1 NT5DC2 TATDN1 MIRH1 TULP3 PARP9 ACE2 SOX11 PABPC1 MCM9 SMA4 DTX3L CEACAM1 HMGA2 MRPL13 MAGI1 PROCA1 BATF2 LY6E PABPC3 NOS1AP MYSM1 RTP4 WARS PTP4A3 ANKRD10 ZNF573 PLSCR1 HTATIP2 EXT1 TNFSF14 JMJD2C APOL3 USP18 TARBP1 SETD6 HERC6 MX2

33 S.Table 3(Cont’d) Module 11 - 44 genes Module 12-41 genes Module 13 - 37 genes COLEC11 HIST1H2BB ZNF813 STAR HIST3H2BB ZNF761 FOXL2 HIST1H2AM ZNF578 GATA4 HIST1H2BE ZNF816A CCDC48 HIST1H2BI ZNF28 EDN3 HIST1H2BO ZNF549 PTPN5 HIST1H2BF ZNF415 PEG3 HIST1H1E ZNF600 TCF21 HIST1H2BM ZNF230 C7 H2BFS ZNF228 ENPP6 HIST1H2AD ZNF223 PRSS35 HIST1H2BL ZNF222 CADPS HIST1H2BG ZNF547 SPRR2F HIST1H2AK ZNF550 TSPAN8 HIST1H2AH ZNF175 SIGLEC11 HIST1H2BH ZNF610 MUM1L1 HIST1H2AB ZNF180 RASL11B HIST1H3H ZNF135 hCG_1990170 HIST1H2BD ZNF606 LAMA2 HIST1H4H ZNF227 GLI1 HIST2H2AA3 ZNF285A ATRNL1 HIST1H3D ZNF471 GATM HIST1H2AE ZNF701 DLK1 HIST1H1C ZNF702 PCSK6 HIST1H2BN ZNF256 TCERG1L HIST1H2AG ZNF582 PLCXD3 HIST1H2AL ZNF83 DIRAS3 HIST1H2BK ZNF772 HSD11B1 HIST2H2BE ZNF667 KLHDC8A HIST1H2AI ZNF766 COL2A1 HIST1H2AC ZNF577 PID1 HIST3H2A ZNF132 TMEM16D HIST2H2AC ZNF542 GPRASP1 HIST1H1D ZNF552 AMHR2 HIST1H2AJ ZIK1 BMP6 OR2B6 ZNF528 WFDC1 HIST1H4J ZNF586 GNA14 HIST1H4B KCNIP1 HIST1H4K MAOB H2AFJ RGS7 HIST1H1T CASR ABCG2

34 S.Table 3(Cont’d) Module 0 - 2635 genes MFAP2 DLEU7 GNAI1 FBL RGAG4 NPNT SH3BGRL2 CDH3 ZNF781 FSCN1 BAI2 MAGEE2 EMID1 ADAMTS6 SPOCK3 CCDC91 SRrp35 MPDZ SLCO1A2 GPR161 CDO1 CHRM2 SLC16A1 IL13RA2 DTNA NTF3 SMAD9 MAP2K6 CFHR4 NBPF1 SYNPR DUSP16 PKIA SNN IGSF3 THSD1 ZNF567 PLAGL2 CCND2 PCDH20 HFM1 CHRM3 HDAC2 SEMA6D SDPR DPY19L2 HS6ST2 EVC2 MARCKSL1 PCOLCE2 TP53BP2 ZNF738 SCG5 SETBP1 C1QTNF4 PRB1 MEX3B PCDH8 GDAP1 RP11-679B17-1 MYLPF SAMD5 TMEFF2 SLC19A2 ZNF711 ARG2 NEK3 PFN3 N4BP2 COL9A2 ANKRD21 MAP3K15 HIF3A AGPAT4 ZDHHC15 SYT13 TSPAN7 IGFALS GABRG2 PPARGC1A ZNF643 MAGED2 TNFRSF19 LPHN2 RIMS3 ZNF608 TAC1 DSCR9 RHOBTB1 IQGAP2 MAGEA9 VCX3A BTBD11 LINGO2 RAD52 PODXL2 SMTNL2 GAS2 LRRTM4 SULT1E1 NEFH THBS3 RAB11FIP4 NPR2 NUDT11 NXF5 GALNT13 VCX2 LRCH2 LYRM4 SNAP25 ART5 CRISPLD1 TREML2 APLP1 FBXO2 DLL3 RBPMS2 ZFP14 IRS1 GRASP PAM NLGN1 PCDHB3 NEURL POTE15 IGSF11 MDK PLEKHG2 ALS2CR11 PRDM5 SLCO6A1 NR2F1 POU6F2 DMRT1 OR3A2 KALRN KIT SYT1 CLUL1 NRXN3 GLCCI1 FNDC5 NOTCH3 DKK3 PNMA3 NELL2 BMF EFCBP1 DLX6 SUPT3H CRYM CYYR1 GLULD1 ZMAT4 PNMA1 FRZB TKTL1 SSX3 FBXO27 GNGT1 LDHB PLD3 WNT11 CHGB DACH2 NDRG4 WNT6 EYA4 ZNF286A TOX2 ELOVL4 SCG3 HIST1H4C PSTK PALM DPP10 DACH1 PENK LY6H AASS WNT5A WDR72 MOGAT1 BLMH KLRG1 DSCR8 PGAM2 IGF2BP2 PLAC1 ZNF229 CSRP3 LRRN1 INA PLEKHG4 CREB5 CNTD1 CCDC23 RNF180 CAMTA1 LOXL3 ECEL1 SARS2 CTNNA2 PPP1R1A CLCN4 CACNB4 OPRK1 NANOS1 CKAP4 ZFP42 ALPL MAP2 RLBP1L1 TMEM155 ZNF571 CLIP3 CXCR7 NELL1 PPM1H PPAP2B PRMT6 IGF2AS ST3GAL5 ATP8B2 PRR4 IFRG15 GPR177 DACT2 VWC2 SLC6A15 REEP1 NLRP1 ERC2 DPY19L2P4 ADAM21 PDE3A CPEB1 NDUFA4L2 PSD2 ZNF232 IL11RA PSAT1 CPXM1 DUSP26 NPY NAP1L2 ANKS1B CDKN1C GPX7 KCNA5 PKHD1 PCDHB6 ERC1 GABRR1 CIC CAPN6 USP44 PNMA5 RAB38 NBEA GLT1D1 SSX7 ZNF257 SLC7A10 DNMT3A LPHN3 DYNC1I1 WSCD2 SOHLH2 SIRT4 ARID3B NOL4 TMEM108 LHFPL1 PCDH9 RAB9B ACRBP AFF2 ANXA6 TMEM98 KCNA4 SV2C ZNF492 LEF1 USP51 ACTBL1 SSX2 KIRREL2 JUB TCEAL2 PLAGL1 BVES LCOR LARP6 PIP5K1B HSPA12A ACVR1C CPT1C NPHS1 ICEBERG BAZ2B EBF4 PRPH CXXC4 SDK1 IGFBP2 STRA6 ING4 SYCP2L IGF2 ISLR2 FYN IQCA LRFN5 LIMS2 ADAMTS18 SLC26A7 PBX2 KHDRBS2 TNNT3 FBN2 MYH10 KCNH3 TAS2R14 PDCL2 XKR6 CEP290 PARD6G CDK6 MAP1B CALCB LEPREL1 GLIS1 ADRA2B NRCAM

35 S.Table 3(Cont’d) Module 0…..(Cont’d) RCBTB2 KREMEN2 HHAT RP13-102H20-1 TUSC3 SOX6 BCL2 GPC4 FGFBP3 U2AF1L4 STON1 ITLN1 PHLPP PRSS1 ODZ4 FSTL5 CST11 SYCP2 RBP2 EFHA2 IRAK1BP1 OSR1 ZNF540 PRKAA2 RGS9 PRKAG3 TTYH1 OXCT2 NSBP1 LOH12CR1 MLCK MAGEA11 LEFTY1 HEY2 B3GNT5 FHL1 ALK PAQR5 TP53I3 RICH2 CAP2 TSPYL5 NSUN7 IL17RB OTC NRG1 ARL4A FGF18 SCN2A RERE AXIN2 AFAP1L2 NPPC FCGRT SLC2A12 PLAG1 STK31 SCGB1C1 TBC1D24 SOX5 ALDH1A1 CNGB3 NGEF LRRC44 ZNF30 HTR2C THAP8 KCNE2 EPHB1 CPLX2 OLFM4 RGN CBX5 WBSCR17 TMEM97 WIF1 PAGE2B WDR40B SPACA3 KCND1 SORCS3 SH3BP4 EMG1 RHCG CR2 HDC WNT16 KREMEN1 DDAH2 CTCFL D4S234E WNT5B LAMC3 PPP1R1C CCNB3 SPG20 GJA12 SLC25A18 STOX2 PCDHB10 ESPNL ATP8A2 CCDC42 HSPA2 NR1I2 TBX2 CDH18 KIF3A LFNG WBP5 BICD1 ACOT6 COL14A1 TMCC2 AKR1C1 RGPD5 ZNF627 MAGEA4 KCNMB2 CST4 TOX3 SOST TRIM6 SCN8A CA10 SH3KBP1 NR0B1 RBM42 ZNF311 PCDHB12 CNTN6 COL9A1 JAKMIP2 TSKS WBSCR28 IGF1R KLHL1 ZNF345 TDRKH PDYN TSP50 ZNF284 PPP1R14A CAND2 NAT8L CD22 PTF1A TNMD XAGE3 COL11A2 PRSS2 EYA1 MACROD2 RBP5 ASCL2 TGFB2 HPN CTNND2 TCP11L2 MLLT4 SLC44A5 RHOU BHMT2 PTPRT PLEKHB1 AS3MT XAGE5 SEMA5B SOHLH1 RIC3 NPY1R TEAD1 CCDC3 SNCAIP GABARAPL1 ICAM4 TDRD5 TCBA1 GFRA2 TRIM58 BHMT ZNF493 KLRF1 NR2F6 HMGCLL1 SLITRK5 HEY1 TM4SF4 EIF2C3 SH3GL2 HORMAD1 EFNB1 NDRG2 ANK2 DSCAML1 CPNE4 GRB10 DNMBP SNCA WNT3 PTH2R CA3 GSTA4 ZNF300 CNKSR3 TCF15 GPR62 PAGE5 SOSTDC1 IL17D LMO3 ULK2 TRERF1 PLXNA4B GDPD2 ROBO3 MT3 LRRN2 FZD10 MYLK2 SULT1C2 DAPK1 GLRA2 VSX1 FREM1 NEDD9 MDGA1 NPY2R ZNF642 ZNF114 RDH12 SSX9 PVRL3 GTF2A1L LINGO1 MAOA SIX2 DGKG HOXA7 RALYL NEBL CUZD1 PAK7 PEPD COL25A1 LHX2 SIM2 CPAMD8 HIST1H4L SCN4B TCAP FBXO41 SPEG HIST1H4D APP PCDHB17 GPR158 GRB14 PHGDH FGFRL1 RFPL2 CRLF1 MAGED1 HOXA9 RAX FILIP1 PCDHB11 C1QL1 MAGEA10 DOCK1 MAGEA1 ZNF235 ABHD8 KBTBD6 ZNF404 KLHL13 PADI3 GRIN2A ARL4C ASGR1 GSG1L GAL3ST1 HSPC159 PRAME RP13-36C9-6 DUSP8 CAMK1D LMO1 SLC26A11 CCIN TOX KCNK17 MARK1 AUTS2 ZNF558 HOMER1 TEX15 ZNF529 KRAS CT45-6 CNTNAP2 HAS3 PDCD2L DKKL1 ITLN2 NEB IMPG2 ZSCAN5 LRRC7 HSD11B1L RSPO3 GAD1 KCNE1L KRTAP4-10 MAGEE1 BHLHB9 MBOAT2 FKBP10 PTCHD1 UBXD7 FGF12 PLEKHO1 FADS2 tcag7-1260 PITPNC1 hCG_1657980 PRKAR2B PYGM SGSM1 IL22RA1 TNNT2 SSX1 KCNH8 EDN2 TSC22D3 SH3GL3 SLC25A21 PNMA2 GSPT2 PAGE2 FGF13 PREX1 CYP11A1 LTBP1

36 S.Table 3(Cont’d) Module 0…..(Cont’d) ZSCAN20 FOXD4L2 HTR1E ROBO1 PARD6B PCSK2 CAB39L POLR3G ALDH1L1 SH3RF1 ID4 LYPD6 PCDHB14 SLC4A4 FBXO21 MFSD2 PON1 CDH19 TP53INP2 WFDC11 CACNA2D1 RXRG SEMA3E MERTK ATF7IP2 FOXA3 LYPD3 UBQLN4 SLC7A9 RTP3 CDKL3 REC8 UST ZNF516 MAEL ASB2 STK32A DGAT2 RPS6KA6 RBM35B CALB1 KCNMB4 PCDHB18 GPATCH2 HES1 TRH FZD5 UGT2B17 CTAG2 SCARA5 MAPK10 NPAS3 ARHGEF10 AQP12B SLC22A15 CRTAC1 CCDC28B NFE2 FGF20 DPYSL2 CD99L2 SHF DAND5 SLMO1 LDHC CSPG5 CYFIP2 LIPF EPHA4 LHX6 NOXA1 LRRCC1 BIVM THRA ANKRD27 RHOBTB2 FOXE1 CBLN2 SNPH ANKRD16 NOTCH1 BAI3 MSI2 BEX2 ANG ANKRD29 COX7B2 CDH22 TMEM99 MC4R REG1A ROR1 GABARAPL3 PDK4 ABLIM1 NSUN6 SIX1 PHACTR2 GDPD5 DOCK6 THSD7A PARD3 tcag7-1136 NES NEDD4L PCDHB2 PCBP4 LPHN1 STXBP5L DYRK4 ATP1B1 MAGEA12 CENTG2 LAYN NXPH4 KCNJ6 CIRBP DSC1 RAB39B ADCY2 MAG FABP3 CHKA TBX4 SFRS6 VAMP1 SLC6A16 C1QTNF9 PNOC CKM GNG4 TNNC1 BEX5 HSD11B2 ICAM2 RBP7 KCNJ3 DMGDH OPN3 RGMA ENPP2 NRN1 MMP26 AKAP3 HIST1H1B PCDH10 FZD3 PCDHB8 ZNF462 WNT10A SPOCK2 ANKRD30A ABHD1 RTN4IP1 UCP1 CNR1 GABRB3 KIF13A ZIC2 PIWIL1 PKNOX2 DPYSL4 AGTR2 USP13 SLC35F3 SYT4 ZNF565 FGFBP2 TTC32 AGRN HIST1H1A KCNS1 CCDC103 CHP2 TMEM44 CENTD3 LIPE ZNF266 SLC2A4 SLC1A2 BRD3 KCNIP4 KRT1 ZNF239 MYH1 DMRT2 KCNV1 HOXA10 PRAF2 PRDM16 ACTL8 NLGN4X SALL4 TMEM121 MALT1 RPRML CA8 PACSIN1 PDE11A NHSL1 GRM8 ZIC5 TMEM22 OIT3 RNF122 PCDHGA3 MAGEA3 AP3B2 EFHD1 GDAP1L1 PKP2 SNTA1 GBA3 LGI1 MGAT3 KY LYZL2 HIP1R ZNF179 ZNF165 SEMA3A CYP17A1 MORC4 RAB33A RPS16 RNF212 CHST3 PASD1 KLHL29 KIRREL3 IL25 ABCC11 GSTM4 ZNF14 ZNF20 GUF1 CDH12 WIZ NHEDC1 LRP1B DKK4 PGM3 ERBB4 SGK2 ATF5 REST TRAF5 PDIA2 BMX YBX2 NOL9 ERO1LB LYSMD1 PLCE1 TIGD3 VIPR2 KSR2 CARTPT TAS1R1 PHACTR3 LTK GALP DFNA5 DNAJC12 CTNNB1 ZNF77 SPRY2 FXYD4 ABCB6 SPINK1 RHOXF1 NPFFR2 PODXL NPW GSTM1 DMRTA1 HSF2BP HTR3C L3MBTL4 JUN ABI3BP GYG2 SPINK2 KCTD15 TBX3 AKAP4 GULP1 ZNF441 CTTNBP2 CD19 KCNN3 APAF1 CST1 TACSTD1 TAF15 CSPG4 SLC20A2 COL4A4 TM7SF2 HES6 RHBDL3 RASD1 NPAS1 SOX13 DOCK3 WFIKKN1 SSTR2 NMUR1 KIF26A DCDC2 TMTC4 AADACL2 BCAS4 CRYGS HOXD10 SULT4A1 TNFSF11 DBC1 RYR2 SCAMP5 RPS23 PVALB FDX1L TMEM16G CNTN5 AJAP1 ANKRD38 SLC2A1 CD200 HOXC5 TSPAN2 STK39 MOSC2 CALML3 ZNF397 TBCCD1 TMEM117 EVI1 DEFB126 NLRP2 PLAT LRRC56 PCDHB7 CPVL ZHX2 HOMER3 ZNF234 PHACTR1 PLXNA2 SLC13A5 ZNF721 ZNF533 PAGE4 RPS26 DSEL SEMA3G TSHR HMBOX1 MTSS1 ABCA4 GOLM1 JMJD2A WASF3 BAHCC1 VEPH1 SLFN13 NR2F2 NKX6-2 IL1F5 DISP2 PKDREJ GPR64 PHYHIP B3GALT1 PLTP MGAT5B ACADL DPPA2 CRYGC AQP6 KCNH2 SLC16A8 MYO3B ZNF790 FGF3 ST8SIA5 MCF2

37 S.Table 3(Cont’d) Module 0…..(Cont’d) RBP1 DPH3 MAGOH LQK1 PPP1R3B PPP2R2C LRRC3B CST9 PCDHA3 SOCS2 RXFP1 ZPLD1 CSTL1 LCN6 CDH1 FLVCR1 B3GALTL HTR1F TBC1D4 TMEM100 ATP6V0A4 AHRR MAS1 PPAT KRT8 ATF3 MIG7 TFCP2L1 PNCK HOXA11 MRS2L ACYP1 MYO10 RPL31 FUT8 SPAG4 LAMA5 ADCY8 DNAL1 TMTC1 ITPKA HABP4 ANP32D ZNF429 LOH3CR2A SMC1B CRB1 SGCG PCDHB16 NXPH2 PON3 OLFM3 EDA KIF21A TNNT1 ATP6V1G2 NXN ZNF226 PELI1 GHRL NTNG1 GPM6B TNNI3 RYR3 CXCR4 NTF5 LY6K LUZP2 PRLR PTX3 TMEM26 SHOX2 SLC30A2 PCDHB15 GBX1 POMC CADM1 NRGN GABRA5 METRNL DET1 PCDHA1 NAT2 AKR1C3 SYCE1 KCNMA1 RPH3AL CASQ2 CLNS1A SLC9A2 LYZL1 DHDH GPC5 ETV5 SPG3A FABP6 SH2D2A ZNF442 KIF12 HYMAI TRIM36 ZNF561 TLE6 ZNF700 AOX1 SERPINA5 BCL11A AKR1B10 JMY HPDL MYBPHL ATP10D CCDC58 HOXB8 PF4V1 ZG16 OXCT1 B3GNT4 SPIRE1 NRTN VIT CRYGD IRS2 MUC15 GUCA2B MAN1C1 BTG2 SATB1 SCLT1 FA2H MAGEC3 TDRD9 ATP6V0E2 MID1 ABR NRG3 DPEP3 TRHDE MEOX1 EPB41L2 HOXA2 PYGL ZNF323 SLC39A2 NMB DAAM1 PIWIL4 LMO7 CAPN9 ACSM3 CREB3L4 SHC3 SPSB2 L1CAM ELOVL3 TGFBR3 CST9L PCDH19 TES REG1B ANKRD13A HOOK2 PTPRM TNFRSF8 B3GNT8 ITGA6 IL23A DUSP2 MCC THNSL2 TMEM25 ZSWIM5 SLITRK2 OGDHL CADM2 CCK DPYS PRDX2 TRIML1 SLC25A41 PLEKHH2 ACY1L2 CCDC73 PCDHA9 COL13A1 HELB REG3G SMPX NTS FGD4 KLK1 STC2 RBM24 MSTP9 RAB15 GATA5 SSBP2 ALOX12 ZNF182 TMEM37 G30 DLGAP1 CHRDL1 RP6-213H19-1 KCNJ16 ELOVL7 PMCH SPERT DPEP1 USP36 NFIL3 LGALS4 SLC16A2 NPR3 TNNI3K DLEU1 TRPM5 GUCA1B CENTB2 SSPO DPPA5 KLK12 ITM2B DBX2 PNPLA1 NR4A1 KCTD19 ZNF440 EDNRB ADAL ENPP3 GDF15 RBP4 SLC27A2 DSP PDZK1 ITPR1 ADSSL1 PLA1A AMOT PNPLA3 SNX16 RAPGEFL1 SPATA19 CCDC122 LSM8 RARB TMEM136 TRAF4 RAP1GAP SERTAD3 RIMS4 PLA2G1B RTN4R RB1 TMPRSS2 SLC13A3 HPGD SBSN HSD3B1 RPS5 TMEM35 PCDHB5 SMR3B RDH10 INHBB TXLNB PABPC4 HOXA3 SYT8 SCPEP1 UVRAG FRMD5 KRT17 NHS GRIA2 ADAT2 PHF8 TM9SF3 CPA6 CMYA5 GRM1 IL17B ERLIN2 HRASLS UNC13C OR7D2 RPS19 ZNF426 POP4 F10 RPESP ITGA7 AFAP1L1 EPS8 OR52E2 PLP2 QPRT FRY HIG2 LRRC4 OR1N1 MAT1A MLLT3 RPL27A ITPR2 PPP1R9A RPL37A UBL5 HS3ST5 SYMPK FBXO16 ZNF233 ECAT8 PTPLA LIMCH1 APLN CYP2E1 DHRS13 FBXW9 PLD1 CCDC144A ZNF564 TMEM16A WDR88 PFN4 HOXB7 ARHGEF18 TLE4 SPRYD5 KLHDC1 TTTY8 TRIB2 CYCS STAG3 ZNF433 HOXA5 SLC16A4 GLIS3 OR4N5 KRT5 GTPBP3 ANKRD25 GYLTL1B SLC38A1 LIX1L TRIM2 ZDBF2 HBA2 ELOVL6 SNTG2 NLRP7 TUSC1 OCA2 FST PROM1 A1BG CBFA2T3 TXK NEO1 ZNF91 GSTM5 TMEM184B NLK SERPINB2 PCDHA5 CRABP1 ADAM5P CNIH3 ZBTB1 SLC39A7 ARHGEF16 NUCB2 A2BP1 MYOM2 GPR143 RET JPH3 ZP1 EIF3K ANXA3 HBD RGS9BP TPO BCAT1 RCAN3 NOTCH2

38 S.Table 3(Cont’d) Module 0…..(Cont’d) GSC LY6D PGBD5 PPP1R14C SCD5 SLC14A1 PTN CRNN APOBEC3D MYCL1 GCHFR PAMCI EGFL11 MET PAR5 FOXA2 OBP2A CDX2 CCDC144B EPHB6 CA9 GSTA2 GSTA5 CDKN2AIPNL CACNA2D3 ANK3 LEMD1 CAMK2N1 ZNF597 ACSM1 NDST3 ACSS1 HIRA CTSF MICALCL HOXB5 WIT1 AFMID UGT2B10 RHOD B3GAT1 RELL1 JAG2 MAN2B1 RAPGEF5 CCDC140 TEAD4 USP35 RABAC1 MMP10 SLC25A29 CNGA1 ADAM32 ZNF485 AR KLHL34 KBTBD11 FOXO1 RRAGD PLEKHA4 KHK OSTalpha NRG4 CDH6 MGST1 ECSIT TP53 PCYOX1L GPR37 ZMYM5 KCNK1 PALMD ANKRD5 FZD8 ZNF383 HS3ST2 USF1 UGT2A3 RASIP1 RIMBP2 RINT1 ABHD12B SCGB1D4 LEPR RHCE PCDHGB2 VSIG2 MFHAS1 GAS8 ZDHHC23 SLC6A12 TLE1 F13B PPBP UBTD1 ARHGAP20 VSTM2L KCTD1 RSHL1 ARL14 SFXN2 SHROOM2 MARVELD3 TCHH GSTA3 HES5 PGR CUEDC1 MMP15 ZNF750 GPER EIF3G ALPP KCNB2 MUCL1 CRYBB2 ATP8A1 CFTR SPESP1 CDH16 RHPN2 TSHZ2 SLC44A3 NLRP10 PPP1R13B MYOM1 NPM3 MOBKL2B SCN9A PHYHIPL RNASET2 DNAJB5 ODZ2 SUNC1 ZNF799 HSP90AA6P GINS4 MAP1D MCTP2 PTPRK MID2 OR4F15 CHST2 COX7A2 ANKRD35 NFIA CNN3 LIMS1 TPM4 PRKCQ MAGI3 DUSP6 OR52N1 LRRC36 ERBB2 KITLG TSHZ1 CGN CHN2 MFGE8 IMPDH2 KLF7 TRAF3IP2 JAG1 MAGEB18 hCG_31916 RPS10 RLN2 IDE FIGF KCNS3 KATNAL2 IL20RB FER BARX2 NOV CKMT2 TBX18 SOD3 OBP2B SYT17 GABRG3 CMTM7 HEXIM1 HBB PTEN SPAM1 SPIN4 IL1R2 UNC5C CTH ATP7A PCDHGA8 RNF144B RAG2 FMO5 PPAPDC1B GLDN DDIT3 SCEL GCDH LGALS8 BNIPL PLCG2 SYNJ2 PITRM1 PIK3C2B OVOL1 PDE9A SLC28A2 TSPAN1 CGNL1 TSPAN3 SLC6A20 MTHFD2 CD163L1 HOXC8 ZNF443 KCTD14 BTBD8 BSND CHCHD7 FUT9 DAZ4 ZNF502 HSZFP36 GRK4 PTS DDC BTNL9 EPHA1 MUC4 STARD10 PRRT3 TCF7 DSCR10 ATP13A4 ASNS MPPED2 MFNG TMEM31 IL1R1 HMGCS2 ZNF655 RAB6B PDE6G MYOC TARSL2 CLCN5 SIVA1 LONRF2 TAF13 RPTN CHGA LRRC37A3 RASSF8 EXOSC5 MSX2 GAL SERPINB7 INSL3 SLC5A3 HLA-DPB2 GNE CYBRD1 ESPN PTGER1 MAGEB3 SEC14L4 PDIA5 LCE1B RASL10A TP63 HOXC9 SFMBT1 DHRS2 FLG EXOC6B UPK3B LIMK1 METTL4 KLRG2 ZDHHC20 STX10 PTPRU ARHGAP23 WWC2 APBA2BP ARNTL2 NFIB SH3BGR AMAC1 GCNT2 LRIG1 ACOT4 NTSR2 MMP20 DDX43 MYBPC2 KDELC2 STRA8 DNASE1L3 INPPL1 ICA1 UGT2B11 RPP25 PROK2 DAGLA BFSP2 C5 CHURC1 LONRF1 LTBR CHRDL2 SH3YL1 SLC7A8 WFS1 KLF4 VILL ABHD9 HAL NAB1 MEIS2 TNNI2 P2RY1 ANK1 DNM1 TNIK HOXA4 THRB CLCF1 RAB12 GNAT2 ABP1 RELN MTMR11 KCNB1 RORA ZC3H12C SEZ6L2 MBNL3 NEUROG2 RDHE2 PHCA ZDHHC2 IMMP1L HKDC1 PCK1 BTNL8 VLDLR ZNF673 SLC44A2 MAP3K1 SYNGR1 PTGDS RPS3 SLC17A5 FDXR CCL28 KRT12 MAL GCNT1 CELSR1 SOX9 CEP72 ICAM5 CRIP2 GPR27 MCOLN2 CCNA1 CSAG1 HOXD9 RIMS2 CLIC6 AKAP5 AMPH PCF11 TMEM79 LGR4 ACRC SERPINE2 ZAK TSPAN33 DEFB123 IER2 QSOX1 PPAPDC2

39 S.Table 3(Cont’d) Module 0…..(Cont’d) SHANK2 FAH MEGF11 ENTPD2 TMEM55A EGFR CCDC90A CYP4F2 IRX5 CLRN3 MATN2 TMEM101 PACSIN3 CPM UNQ9368 BPNT1 MAB21L2 S100P CDH15 TLE2 AQP3 RPS29 ZNF238 FOXD1 KCNQ1 STAT6 EPN3 AGR2 CACNG1 ADORA2B HOXD8 CHORDC1 XKRX FXYD5 ADCY3 GSTT1 PELI2 ARHGAP4 TMEM166 ACCN1 N6AMT1 POU5F1P4 SERTAD4 HOXB2 MRPL4 ADAMTS1 PPP2R2B hCG_16001 RPL36 TRIM15 CARM1 AADAC DIRC1 PRSS36 STC1 CPO GPR126 DDEF2 ACOX3 RFESD PPFIA3 CRYL1 CD81 NKAPL TMEM16J CRABP2 BMP8A XK CDKN2A CMTM1 SLITRK6 CD109 KCNK5 RANBP17 ZBTB44 ATP2C2 SPATA13 ANKRD15 CLYBL EDN1 HS6ST3 PRSS21 CSAG3A TM4SF19 MIA NUDT13 SQLE CLDN4 SEPW1 IL27 IFLTD1 ELK1 PDLIM4 ATP5I WBSCR27 CECR6 DIRAS2 CST6 UNQ501 GUCY1B2 GPD1 VEGFA ABCA5 PRRX2 ANGPTL4 STAC XG ADM CLGN GPHN BPGM CADM3 STYK1 TBL1Y BCAR3 KRTAP5-8 ANXA8L2 PTGS1 JDP2 RASEF LYPLAL1 CLPS H1F0 LNX1 SLCO3A1 DYRK3 SLC38A2 PTPRS ZNF563 QTRT1 HGD MYOZ2 CYB5D2 ZNF480 TMPRSS5 PRSS33 AKR1D1 SPINK6 TPT1 HSPB2 CLDN23 F12 FOXA1 KRT15 UBB CNDP1 ZNF497 CAPN13 UNQ9433 HOXB6 HOMER2 CTAGE4 PRUNE2 ZNF556 PRSS8 TMEM54 TUBA8 WWTR1 ANXA9 DNAJC15 MC1R BRAF ABCA13 TMEM159 TMEM92 EGR1 LANCL3 SIAE SKAP1 HSPA1A ST14 MAP3K8 ALOX15B LYG2 PSORS1C1 BCMO1 HYAL3 IPP EEF1B2 CPB1 NEU1 UGT2B28 MESDC1 METTL7A UNC5CL CENTD1 HES2 UNC84B HIBADH CITED2 PERLD1 ChGn GMPR SCGB1A1 NEU4 USP43 ATAD4 DUSP27 LETM2 RPS25 WFDC3 DGKB SARM1 GAA TBL1X RALGPS2 AP1M2 TAX1BP3 ERICH1 GLDC STAC2 DAPL1 HIATL2 ANKRD37 MTUS1 P2RY2 SH3BP5 PGM1 ROS1 GADD45G LDHA OXTR BDNF BAI1 WISP3 TM7SF4 PHEX TCF20 UGT2B7 GALNT6 DEFB103A ALDH2 ATP5G1 USP28 RPL9 HOXB3 FOXD2 SNTB1 LGALS14 ADCYAP1 GALNT12 SLC25A38 STBD1 KRT13 LYPD1 LRRC2 KRT6B IFNE1 ST6GAL1 ADRA2C LDOC1 GPR81 ZFAND2A BOK TSPAN31 CBS C1GALT1 CLMN OCIAD2 MED18 CAMP PNLIPRP3 ALG8 AREG LIMS3 GCNT3 GRHL2 COL17A1 COX18 POF1B C1RL NPTX2 AXUD1 RPSAP15 ARL4D ARRDC4 TNS4 CYP4X1 S100A4 CFI BAIAP3 LRP11 FRMD3 OR5B12 CHMP4C GGTLA4 NRG2 DUSP5 ST20 CARHSP1 LYPD5 SPIN2A GTF2IRD2 NQO2 IL27RA ATP12A TRIM17 PTGS2 CCDC68 IGSF10 GRHL3 CLDN1 ECHDC3 TPD52L1 ACOT2 LMO4 PCDHGB6 STK32B SLC16A9 RPS6 ENOSF1 NAPG LIFR NR4A2 VSTM1 LMCD1 RERG hCG_2001000 ALPPL2 FKSG2 VHL SERPINB6 KLHL2 RIPK4 APOC4 SPAG11B NFYA TENC1 CTSE RPL22L1 GK5 CRISP3 CSDA TEX12 ZNF581 SEMA3F GRB7 EREG RPL18A PRKCA PORCN EIF3E APOBEC3B PHYHD1 EPHX2 VWCE PLSCR4 REN DECR1 ST6GALNAC2 ATPIF1 SERHL CRISP2 RPS28 ERP27 MITF ALCAM EPS8L1 IGFL1 KLK13 COL23A1 GATA6 RBBP8 SPIN2B PCDHGB7 CYB5R2 AMFR RPSA LONRF3 PIGZ DIAPH2 ZNF33B KRT18 PERP REPS2 NUDCD1 ADAM28 ETV4 TFF3 MUC13 LAGE3 ANXA4 GOLT1A NDUFB7 TRIM73 FBXO25 FCHO1

40 S.Table 3(Cont’d) Module 0…..(Cont’d) TRAPPC6A MACF1 OLFM1 ME3 PIK3R3 OSBPL3 SPAG1 MYC GSN SLC7A11 SLC7A2 PIR ACY3 WNT7B TMEM61 SLCO1B3 NOXO1 PTPN3 NMNAT2 PRSS12 MFI2 BAG1 TGM1 CHI3L2 TMEM65 NAT1 TCEA3 SFTPG ARP11 TRA16 CYP21A2 CMTM8 KRCC1 hCG_25371 SSPN CD97 KLK11 PSCA EGLN3 TNFRSF18 CENPP UQCRH SLC9A3R1 HOXD1 INSIG1 RAB25 MUC20 GLYATL2 SYTL4 CD1B HDHD1A ZNF774 MPP7 BCL6 RTN4RL1 NPAS2 CALML5 EYA2 SOX2 UNC13D PTGES SMARCD2 SDCBP2 A4GALT SLC1A1 GAB2 LTF ST6GALNAC5 KRT19 KLK6 EBP ALOX12P2 VPREB3 ARHGEF10L SCGB2A1 CRIP1 EPHX1 FGFBP1 RNF183 METTL7B HSD17B12 GALNT14 BTG3 LAMA3 ZADH1 MT1G METRN ASRGL1 ATP6V1B1 ZBED2 CR1L SPON1 STXBP6 CHST6 PKHD1L1 FAT2 GPRC5A CD1E GPR110 SUSD4 SIPA1 FOLR1 CRB3 DEFB4 FHL2 SYNE2 CCDC6 DMBT1 CORO2A NXF3 PPARGC1B FXYD3 TBC1D25 HLA-DRB6 PUSL1 SCD ENY2 STS-1 UCP2 CYP4F8 FJX1 GJA3 GADD45A RBM35A WDR45L LAD1 PXMP4 HRASLS3 SDF2L1 TIPARP PRKY PRKX PARVB S100A2 ZFAT1 TNFRSF11B LYPD2 RBPMS ITGA3 MAPK13 CXCL3 GPRC5C ST6GALNAC1 PKP3 IER3 ANXA13 LARGE CITED4 ERBB3 ASPHD1 DOK5 FMR1 SCNN1A TSPAN15 SH3RF2 MYO5B NMNAT1 MOGAT2 CYP4F11 ICAM3 TMEM45B OAZ3 RNF150 PFKFB3 PFKP NUDT2 ANKRD2 SH2D4A SLC27A5 CDC42EP2 FZD4 DIO1 CYP3A4 MYEOV MTCP1 SSR4 DCXR PTPRR TRAPPC2 NIPA1 THSD4 SMARCD3 STAP2 RAPGEF3 TGFA GABBR2 THG1L HOXD3 PGM2L1 TMEM141 SERPINA3 RASL11A SELENBP1 SHROOM3 TRIM4 HSD17B8 TMEM125 TG CDKL1 ZNF185 TRIM59 GSR CCDC110 LRRC8E CYP3A7 LIPC SNCG SUSD3 GNG7 UNQ338 NDP WDR4 SLC44A4 CATSPER3 KLK8 ALDH3B2 ANKHD1 NR2E3 PPP1R1B PHF15 KRT6A GJB5 OR2T2 DEPDC6 RGS10 KRT14 TMPRSS3 C4BPA PPM1J SLC23A1 GDPD3 FUT3 TMPRSS13 MBOAT1 BAIAP2L2 APOBEC3C CYP3A5 FAAH2 ITGB3 TMEM40 CLDND2 TRIB1 ST6GALNAC6 MOCOS AGPAT2 DPP7 SMARCA2 PHLDA2 P11 LRAP FOLR3 ACP6 SPTLC3 HPRT1 MT1E PIM3 NOL3 TRIM38 KCTD9 EML2 GSTZ1 LAMC2 FNBP1 ENDOD1 SDSL PDHA1 ZNF630 SLC15A2 ITGA9 TJP2 CDR2L GOLSYN FOXC1 RPS14 RHOF RAMP1 S100A7 ATP10B KCNN4 LOH11CR2A CALN1 SLC16A6 GPR56 SLC26A9 CEACAM6 CLDN7 ADPRHL1 TCN1 PRKAG2 PPFIBP2 THRSP ATP6V1C2 BACE1 SLC35F2 CPEB3 MYL5 ITGB8 PRRG1 ESR1 CHST4 EMP2 NEIL1 DDIT4 HP B3GNTL1 ZNF780B RDH5 KRT6C APH1B IL1A PPAP2C CA12 HRSP12 RAB11FIP1 HAGHL ZP3 KRT7 HCG27 TEP1 CPNE2 GRTP1 TRPM8 SLC16A5 CDKN2C KRT33A PRRG2 S100A7A NUDT18 SCML1 TMEM129 ABHD7 JUNB AMY2A DOCK9 ALG13 MMEL1 HEBP2 NY-REN-7 AMY2B GPD2 TFAP2A AIFM1 RAB40B PCBD2

41 S.Table 3(Cont’d) Module 0…..(Cont’d) TMC4 DEFB1 PAEP ROM1 CLDN10 TRIM47 MB TFAP2C TACSTD2 MUC16 SLPI RAB3D COX7B ARHGAP26 PVRL4 S100A13 TTC35 SAA4 ABHD11 STEAP3 PLEKHA6 GJB1 KRT16 COMTD1 TMPRSS4 TMEM187 GPT FUT2 LIPH PTK6 RNF39 SFN EBAG9 TRPM4 ELL3 CD82 CYP4B1 TMEM24 LTC4S ZDHHC24 SCARA3 BACE2 FER1L3 DAPK2 PIP RNF125 CARD14 S100A1 SCGB2A2 MAL2 AHNAK ASS1 NPR1 MPZL2 PRSS16 BSPRY SPR NXNL2 PROM2 SH2D3A LDLR S100A14 SUSD2

42 Supplementary Table 5. Class Functionalities based on Enriched Module Genes

Class 1 Class 2

Module 1a Module 6 Module 11 Module 1b Module 3 Module 9

Interferon signaling - IFI35, IFI44, IFI44L, Development, cell fate Embryogenesis & Innate - Adaptive IFIH1, IFIT1, IFIT2, IFIT3, and differentiation Development – STAR, ECM – COL5A1, Immunity / Tumor cell OAS1, OAS2, OAS3, pathways- GDF10, Cancer Testis FOXL2,BMP6, COL5A2, SPARC, escape from Immune OASL, GBP1, GBP4, ZNF423, COL9A3, Antigens - TEKT1, ABCG2, AMHR2, VCAN, COL1A2, surveillance- HERC5, HERC6, XAF1, TEX101, COL4A6, LRP4, SPEF1, SPAG8, DLK1, DIRAS3, EDN3, FBN1, FN1, COL1A1, HAVCR2, LCP2, SLA, MX1, PARP9, RIG-I, LRP6,SMO, ZNF219, WDR16, ROPN1L, GATA4, HSD11B1, ITGA11, DCN, LILRB3, TNFAIP8L2, PARP14, IDO1, ZBED3, ZNF219, TCF7L1 , CCDC65, TSNAXIP1 GLI1, PEG3, PRSS35, COL6A3, COL6A2, LAPTM5, HCK, CXCL11,DTX3L, RTP4, TUBB2B, Sox12, RASL11B,WFDC1SPR COL11A1 TNFSF13B SAMD9,SAMD9L, NMI, CCNB1IP1, CECR2 R2F, TSPAN8, ISG15, PLSCR1, TRIM22, UBE2L6 Cell adhesion, actin Cilia & Dynein Hematopoietic cell Antigen processing remodeling, metastases related – IQUB, surface molecules & EMT, Cell Migration & MET, Adhesion, and presentation - - CLDN19, ENAH, RSHL3, Hematopoiesis – Invasion – SNAI2, Differentiation – HLA-A, HLA-B, HLA-C, CAMK2B, LAMA1, TTC29,DNAH7, CD45, CD48, CD53, LUM, THBS2, MMP2, TCF21, CDHR1 HLA-E, HLA-F, HLA-G, MYH6, MYH7,BSN, CCDC135, GAS2L2, CD305 / LAIR1, FAP TAP1, PSMB8, PSMB9 MAPK4, CHST10 WDR63 MNDA Cell cycle / quiescence/ Inflammation, ROS, Tumor suppressor / ECM, Invasion- G-protein receptor Cytokine mediated Tumor suppressor – Stromal Cells Related genetic instability – associated - PCSK6, mediated siganling– Lipid movement / ZMYND10, CCDC19, – INHBA, WISP1, USH1C, HHATL, TSPAN8, LAMA2, CYBB, NCF2, Binding - APOL3, DLEC1 PDGFRB CACNA2D, KIF1A, MST1, ATRNL1 GIMAP4, TAGAP, APOL6 SALL2, RP4-691N24-1 ARHGAP9 Transformation Chromatin remodeling, associated (i) Tumor transcription, stem cell suppressor – BATF2, G-protein signaling CAMs, Formation of Adhesion, activation, development (ii) Oncogenes - ETV7, – CASR, GNA14, platelet plug – Differentiation - - ZNF10, JARID2, (iii) Mestastases – GPRASP1, RGS7 PLEK, ITGB2 CDH11 SALL2, ASXL3, PHC1, LAMP3 , (iv) Cell CXXC6 / TET1 Adhesion and polarity - ZBP1 Post-translational Pluripotency and Complement – C7, modifications – quiescence – COLEC11 B4GALNT4, MEX3A GMFG,,SLA, ABI3 Regulation of innate / adaptive immune responses - SRCRB4D

43 Supplementary Table 6. Ovarian cancer cell line datasets

Dataset Cell line Platform Silhoutte-based Reference Classification GSE26634 OAW42 Agilent Whole Human Genome Class 1 Fejzo et. al, 2011 Microarray 4x44K GSE27257 OVCAR3 Human SMD Print_1360 Class 1 O’Brown et. al., 2011 GSE27257 HEY Human SMD Print_1360 Class 1 O’Brown et. al., 2011 GSE27257 OV90 Human SMD Print_1360 Class 1 O’Brown et. al., 2011 GSE27257 2008 Human SMD Print_1360 Class 1 O’Brown et. al., 2011 GSE18054 A4 Agilent Whole Human Genome Class 2 Bapat et al. 2010a Microarray 4x44K - CP70 Affymetrix U133 Plus2 Class 2 Bapat et al. 2010b GSE3001 SKOV3 CodeLink Human 20K ver4.1 Class 2 (outlier) Komatsu et al. 2006

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Supplementary Figure. S4. Representative Wound Healing Assay Images

Supplementary Figure. S4. Representative Images analyzed using the software – Tscratch of - A. OVCAR3 B. OAW42 C. A4 and D. CP70 cells undergoing Wound Healing at various time points post wound induction. Row A (Media without additives), Row B (5% FBS), Row C (5uM LPA), Row D (5uM LPA+5% FBS), Row E (10ng/ml TGF), Row F (5uM S1P), Row G (10ng/ml EGF). Bar scale is 500um (shown Row A, 0 hr).

45 Supplementary Figure S5

Supplementary Figure. S5. Graphical representation of wound healing efficiency of OVCAR3 & A4 cells (left and right panels respectively) including effects of additives as indicated. Data represents wound area healed relative to initial empty area as detailed in Fig.S2. Each experiment was carried out in triplicate; * p<0.05; ** p<0.001; *** p<0.0001.

Supplementary Figure S6

Supplementary Figure S6. Representative immunofluorescence image of Class2 invasion in matrigel sandwhich culture in which two A4 spheroids are evident along with cells invading towards the bottom of the dish; a. nuclei stained with Hoechst (blue); b. E-cadherin (green); c. Vimentin (red); d. merge of a,b,c. Scale bar is 100 μm.

46

Supplementary Figure S7

Supplementary Figure S7. Representative Immunofluorescence expression images of markers for FTE (PAX8), ovarian stroma (PEG3), MET (TCF21); EMT (Slug); Red-Cy3 labeled secondary antibody; Blue – nuclear staining with Hoeschst.

SupplementaryTable 7. Correlation between tumor samples in TCGA subtypes and MW classes

Class1 (77) Class2 (99) Class3 (51) Proliferative 59 4 4 Mesenchymal 1 53 5 Differentiated 10 11 28 Immunoreactive 0 31 13 Unclassified 7 0 1

Supplementary Table 8. Correlation between tumor samples in MW classes and iE-iM subtypes

Class Class 1(77) Class 2(99) Class 3 (51) iE 61 20 30 iM 4 79 6 NT 12 – 15

Not classified (NT)

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