FANTOM 5: Discovering TSS-specific transcriptional regulation

<p>We use the FANTOM5 data in order to check for the existance of transcirption start site (TSS)-specific regulation. We apply our proven methods to reverse engineering the regulatory network controlling TSS-specific expression.</p

Schematic representations of the CINDy algorithm.

<p>A collection of gene expression profiles is required to calculate Conditional Mutual Information between lists of modulators, transcription factors and putative target genes, with the final output of inferred modulation events.</p

Default parameters used for running MINDy.

<p>NA: Not applicable.</p><p>Default parameters used for running MINDy.</p

Alternative three-way network topologies including a Transcription Factor (TF), a Target gene (Tg) and a Modulator gene (M).

<p>(A) depicts the independent regulation of the target gene by a modulator and a TF; (B) describes a three-way interaction between the TF, the target gene and the modulator.</p

Example of novel prediction by CINDy.

<p>Proposed mechanism for modulation of HMGA1 by CDK2.</p

Comparative performance of MINDy and CINDy.

<p>Precision and recall values are compared in the B-cell lymphoma dataset (panel A) and Lung Adenocarcinoma dataset (panel B), calculated by matching the predictions with a gold standard dataset set obtained from four different databases of experimentally validated PPIs between modulators and transcription factors. Precision and recall are further compared at different robustness threshold for MINDy (blue line) and CINDy (red line) in the B-cell dataset (panel C) and in the Lung dataset (panel D, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109569#s4" target="_blank"><b>Materials and Methods</b></a>).</p

QQ-plot (panel A) and GSEA plots (panel B) of the KEGG ABC transporter pathway.

<p>The QQ-plot is constructed using the genotyped SNPs whose snp-map contains at least one ABC transporter pathway gene. The GSEA plot shows the enrichment score of the ABC transporter pathway. The top portion of the plot shows the running enrichment score for the pathway genes as the analysis moves down the ranked list. The peak score is the enrichment score for the gene set. The bottom portion of the plot shows the value of the ranking metric as it moves down the list of ranked genes. The plots for the other two enriched pathways (Proteasome and Propanoate metabolism) look similar (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131038#pone.0131038.s002" target="_blank">S2 Fig</a>).</p

Key steps of the Pointer algorithm.

<p>Key steps of the Pointer algorithm.</p

The top REACTOME pathways enriched in differentially expressed genes from SJS/TEN active lesions and ranked by FDR (FDR<0.25).

<p>The enrichment score is computed by DAVID on the 200 DEGs from Chung et al. Abbreviations: #GENES (number of DEGs in the pathway), PV (p-value, Fisher Exact test), FE (Fold Enrichment), FDR (false discovery rate). A (*) next to a pathway name indicates that the pathway was found to be enriched by both Pointer and DAVID.</p><p>The top REACTOME pathways enriched in differentially expressed genes from SJS/TEN active lesions and ranked by FDR (FDR<0.25).</p

Enriched Reactome pathways ranked by FDR.

<p>In capital letters, pathways that contain KEGG proteasome genes.</p><p>Abbreviations: GSS (pathway gene set size); GLE (number of genes in leading edge); ES (Enrichment score), NES (Normalized Enrichment score), PV (p-value), FDR (false discovery rate), SD (p-value of shadow analysis against KEGG proteasome pathway)</p><p>Enriched Reactome pathways ranked by FDR.</p