Higher order of endometriosis gene-expression, chromosome 1q significantly contributes to endometriosis specific gene-expression, meta-analysis of three (3)independent endometriosis studies
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Endometriosis gene-expression, meta-analysis
1. Gene-expression in Endometriosis: Chromosome 1q significantly contributes to endometriosis gene-expression MehisPold, M.D. Founder EOMIX, Inc. August 9, 2010 8/9/2010 1 mehis.pold@eomix.com
2. Endometriosis (from endo, "inside", and metra, "womb") is a medical condition in which endometrial cells are deposited in areas outside the uterine cavity. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones. Endometrial cells deposited in areas outside the uterus (endometriosis) continue to be influenced by these hormonal changes and respond similarly as do those cells found inside the uterus. Symptoms often exacerbate in time with the menstrual cycle. Endometriosis is typically seen during the reproductive years; it has been estimated that it occurs in roughly 5% to 10% of women. Symptoms depend on the site of implantation. Its main but not universal symptom is pelvic pain in various manifestations. Endometriosis is a common finding in women with infertility. Source: Wikipedia Terms: Ectoendometrium – endometrial tissue outside of it’s natural location Euendometrium – endometrium in it’s natural location, uterine cavity 8/9/2010 2 mehis.pold@eomix.com
3. Diagnostics of Endometriosis: INVASIVE - Confirmed by laparoscopy Exclusion of other conditions Systemic diagnostic markers poorly understood Medical need for non-invasive diagnostic test How do we find endometriosis markers? Blood Urine Saliva Skin biopsy Hair follicles 8/9/2010 3 mehis.pold@eomix.com
4. (1) Meta-analysis of three independent whole-genome expression sets (2) GenMAPP pathway analysis Endometriosis database of EOMIX Inc. 8/9/2010 4 mehis.pold@eomix.com
5. Summary Statistics of Endometriosis sets (Roth, Klinkova, Hull) Pathway analysis by GenMAPP on genes altered in at least two of out three Endometriosis datasets N = 2,522 = Venn diagram [2+3+4] R = 19,632 8/9/2010 5 mehis.pold@eomix.com
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8. GenMAPP Overview Small amount of information does not produce reliable results Results depend on Gene Ontology hierarchies and the existing pathway information Z-values greater than 2 and smaller than -2 considered relevant Z < -2 and Z > 2 Examples at R/N= 0.128 (12.8%) n = 90 pathway of 90 known members, r = 30 of which 30 are altered r/n = 0.333 (33.3%) Z = 5.82 n = 9 r = 3 r/n = 0.333 (33.3%) Z = 1.83 = insignificant 8/9/2010 7 mehis.pold@eomix.com
78. Metabolism and Cell cycle appear low in endometriosis as compared to normal endometrial tissueConnection to previously published studies Plasma cell infiltration ~ high levels of B-cell receptor gene-expression documented in previous studies. Heveret al. (PNAS, 2007) documented plasma-cell infiltration of ovarian endometriosis. 8/9/2010 10 mehis.pold@eomix.com
80. Chromosome 1q32 genes that exhibit altered expression in endometriosis Red font and blue font denote up- and downregulation, respectively 8/9/2010 12 mehis.pold@eomix.com
81. SUMMARY Pathways modulating host defense are activated in endometriosis Chromosome 1q significantly contributes to endometriosis gene-expression 8/9/2010 mehis.pold@eomix.com 13