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MSM is a developmental category generated by public health officials and deployed by NGOs as part of outreach services catering to indigent male populations considered to be "at high risk" for HIV infection.
We have identified a novel Mendelian disorder characterized by a congenital insensitivity to pain, loss of touch sensation and severe cognitive delay, which clearly fits into the developmental category and hence defines a hitherto unrecognized human gene essential for pain perception and CNS development.
Furthermore, the well-known miR-302 cluster and even a single miRNA, miR-294, also target modules functionally enriched in the developmental category with respectively corr p-value <1.4436E-21 (Fig. 3a- 3b), and corr p-value < 1.0157E-29 (Fig. 3c- 3d).
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Only general developmental categories, such as "Cell Growth and Proliferation", were associated with this parental, density-enriched cardiopoietic population that inevitably contained confounding cytotypes.
Analysis of the biological processes in the beating EBs confirms these observations, with overexpression of embryonic and organ system developmental categories including nervous system development, kidney development, skeletal muscle development, and heart development (Table S2 (A8)).
The majority of results were comparable regardless of the algorithm used (Table 8), with a small number of exceptions: endothelial-specific and developmental categories were only found significant with GSEA and not OntoExpress, and categories relating to transcriptional and translational processes were identified with OntoExpress but not GSEA.
In contrast to cell cycle and developmental categories whose enrichment in both transgenic and tumor gene sets reflects progressive regulatory alterations during carcinogenesis, downregulation of genes associated with protein deubiquitination, a relatively new target for cancer therapy, was first observed in tumor cells.
In general, H3K4me3 fractions displayed over-representation in metabolic processes while H3K27me3 fractions showed enrichment in developmental categories.
In contrast, genes up-regulated in Taf9b KO cells were enriched in categories such as vascular development, stem cell maintenance, and other non-neuronal developmental categories.
Publicly available Serial Analysis of Gene Expression (SAGE) data was used to group Giardia genes into 6 developmental categories and one category for constitutively expressed genes.
P-values for enriched developmental categories were transformed into their –log values and used to generate significance plots, to visualize prioritization in CALR-variant transcriptomes.
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