001 these gave a weak but significant positive correlation (r = 0.1, P < 0.05). selleck chem inhibitor Unbiased genes were not significantly correlated with connectivity, nor were the brain genes, as may be expected given the dilution problem of brain expression mentioned above. This trend also held true when using fold-change as a measure for sex-bias. In other words, sex biased pathways seemed to generally affect local components of the network, except for the ones overexpressed in the male adult gonad, which tends to act more often in global components.Table 3Sex-biased genes tend not to be hubs. This is evidenced by Spearman’s correlation coefficient between differential expression (measured as MWT FDR) and network connectivity which was significantly positive in most cases. Sex-biased genes were separated ..

.3.3. Sex-Biased Hub GenesFrom the previous section it is clear that the level of sex was a function of both by tissue/stage condition as well as connectivity. We demonstrated that low connectivity genes tend to be more sex biased than high connectivity genes, yet some hub genes have strong sex bias. To focus on such sex-biased hubs, we first ranked each gene according to sex bias or connectivity separately and then reranked them according to the sum of both ranks. The highest ranked genes thus represent the most sex-biased hub genes. Table S3 shows the twenty top ranked sex-biased hubs in each condition.Among the highly connected hubs in Table S3, tubulin alpha-3e (TUBA3E), ranked first and second in the embryonic and adult gonads, has 426 links.

It is female biased in the embryonic gonad but male biased in the adult gonad. Other highly connected tubulins are also in the list. This indicates that sexual differentiation and sex-specific function are partly orchestrated via sex-specific tubulin assembly. Some of the proteins in Table S3 are directly implicated in sex determination, for example, the testis-specific tubulin alpha-2 (TUBAL2, connectivity 94), the meiotic recombination SPO11 (connectivity 37), or the NASP the nuclear autoantigenic sperm protein (connectivity 97). A major hub in the embryonic as well as the adult gonad is CDK3, cell division protein kinase 3 (connectivity 189). CDK3 is further linked to the KEGG pathways oocyte meiosis as well as progesterone-mediated oocyte maturation. Intriguingly, CDK3 was strongly female biased in the embryonic gonad but strongly male biased in the adult gonad.

Overall this suggests that a major difference between the sexes results Dacomitinib from a complex interplay between components of the cell division and development systems.3.4. Interconnectivity of Sex-Biased GenesTo answer the question if sex-biased genes are stronger connected to genes of the same bias, we compared the connection frequencies between the different categories to what is expected by chance alone.