Quantification of miRNA-mRNA Interactions

miRNAs are small RNA molecules (′ 22nt) that interact with their corresponding target mRNAs inhibiting the translation of the mRNA into proteins and cleaving the target mRNA. This second effect diminishes the overall expression of the target mRNA. Several miRNA-mRNA relationship databases have been deployed, most of them based on sequence complementarities. However, the number of false positives in these databases is large and they do not overlap completely. Recently, it has been proposed to combine expression measurement from both miRNA and mRNA and sequence based predictions to achieve more accurate relationships. In our work, we use LASSO regression with non-positive constraints to integrate both sources of information. LASSO enforces the sparseness of the solution and the non-positive constraints restrict the search of miRNA targets to those with down-regulation effects on the mRNA expression. We named this method TaLasso (miRNA-Target LASSO)

KEGG pathway enrichment results for LDS dataset.

<p>Enrichment analysis on KEGG pathways of the 200 top-ranked genes. The figure shows the results for TaLasso, GenMiR++ and Pearson Correlation. In the figure, the x-axis indicates the number of mRNAs on each enriched pathway. The associated p-value is also shown. The list of genes on each enriched KEGG pathway is included in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030766#pone.0030766.s004" target="_blank">text S2</a>.</p

MSE errors for Cross Validation analysis for <i>global tuning parameters</i>.

<p>In the figure the LOOCV mean squared errors for different κ values of the <i>global tuning parameter</i> for MCC and LDS datasets are shown.</p

Maximum enrichment values on experimentally-validated targets for MCC dataset.

<p>The table shows the maximum enrichment values (point of minimum p-value) for the union of TaRBase and miRecords, for MCC dataset. N_E: is the number of experimentally-validated targets rescued in the point of minimum p-value and N_T: is the total number of predicted targets in that minimum. N_E⁵⁰⁰: is the amount of experimentally-validated targets in the first 500 predicted interactions.</p

Maximum enrichment values on experimentally-validated targets for LDS dataset.

<p>The table shows the maximum enrichment values (point of minimum p-value) for the union of TaRBase and miRecords, for MCC dataset. N_E: is the number of experimentally-validated targets rescued in the point of minimum p-value and N_T: is the total number of predicted targets in that minimum. N_E⁵⁰⁰: is the amount of experimentally-validated targets in the first 500 predicted interactions.</p

Shared interactions among the different databases of human miRNA targets that have been used as initial set of putative interactions.

<p>The overlap among the different databases is small. With reference to databases with experimentally-validated targets, the union of miRecords and TarBase includes 623 interactions that are also cited in any of the computationally predicted databases. This number rises to 4372 in case miRWalk is also considered.</p

Predicted experimentally-validated targets and the cancer to which they have been related in the literature: results for LDS dataset.

<p>CLL: Chronic Lymphoblastic Leukaemia, ALL: Acute Lymphoblastic Leukaemia, AML: Acute Myeloid Leukaemia, IC: Immunce Cells, IR: Immune Response, HSC: Haematopoietic SC.</p><p>The experimentally-validated targets included in the top 500 targets predicted were selected and their literature references included on TaRBase, miRecords and miRWalk were analyzed in search of biological relevancy. In the table only those interactions with a literature reference related with LDS environment have been included. This was made for the predictions of TaLasso, GenMiR++ and Pearson Correlation.</p

Enrichment on experimentally-validated targets for LDS dataset.

<p>For each value of the tuning factor and different number of predicted interactions, the figure shows the probability of drawing the predicted number of experimentally-validated targets by using a hypergeometric test. The figure shows TaLasso enrichment results for different <i>κ^G</i> values (in blue), compared to the enrichment values of GenMiR++ (black crosses) and Pearson Correlation (black dashed).</p