d in Table 2. miRNA Indirect Functional Analysis Since miRNAs are not included in any ontology data base, we performed an indirect functional analysis by screening the functional terms associated with the experimentally validated target coding genes of the miR NAs, extracted from TarBase. Once the target nno tated via GO terms or SP keywords, as above. mRNa miRNA Complex Functional Annotation We then checked the functional classifications coher ence between the indirect and direct functional analysis, within each significantly annotated factor. Thus, globally speak ing, F1 annotation is unchanged and related to functions that are responsible for signal transduction.

In F2?, 3 out of 7 target coding genes are annotated with terms that can be asso ciated to the categories significantly varied in the mRNA functional analysis, F2? is then confirmed to be a factor involved in functions related with adhesion and or che motaxis. For the miRNAs in F3, 5 out of 8 target cod ing genes are functionally related with the gene Batimastat expression term found in the mRNA functional analysis. Interestingly, most of the terms are related with mechanisms of transcription regulation and only one with protein ubi quitination. After direct and indirect annotation, 2 miR NAs and 31 human coding genes in F3 were selected as belonging to the same category. Not surprisingly, most of the coding genes in this list are not predicted to be targets of the 2 miRNAs that appear in the factor. In fact, the biological meaning of the result is a set of genetic elements that share cov ariability in the expression pattern and we know that, e.

g. in animals, most of the control on gene expression is performed by tuning translation. Therefore, the levels of miRNAs and the mRNAs of direct targets are not directly correlated. As it is also suggested in we can imagine that our list of coding genes contains the possible subset of indirect targets of two miRNAs, miR 17 5p, and miR 20b. Globally, F3 is confirmed to be associated with gene expression, with transcription regulation being the most common mechanism of expression. Emergent Properties Since the transcription regulation term appears to give the clearest biological information, coherent in mRNAs and miRNA, we focused our efforts on this part of the analysis. The total sets of mRNAs and miRNAs returned from this analysis are listed in Table S6 and S7 of the Additional file 1.

Latent Structure Chromosomal Loca lization, Most of the miRNAs in F3 belong to two poly cistronic miRNA genes where miRNAs are lying in close proximity on the chromosome. These polycistronic miRNA genes are involved in cell proliferation, apoptosis suppression, tumor angiogenesis and T cell leukemia. The first polycistronic gene is composed by 7 miRNAs and maps on Chromosome 13 whereas the second one maps on Chromosome �� and contains 6 miRNAs, details are shown in Figure 1. The two clusters are closely related, in fact, each miRNA on one cluster has at least one homologo