A Set of Structural Features Defines the <i>Cis</i>-Regulatory Modules of Antenna-Expressed Genes in <i>Drosophila melanogaster</i>

<div><p>Unraveling the biological information within the regulatory region (RR) of genes has become one of the major focuses of current genomic research. It has been hypothesized that RRs of co-expressed genes share similar architecture, but to the best of our knowledge, no studies have simultaneously examined multiple structural features, such as positioning of <i>cis</i>-regulatory elements relative to transcription start sites and to each other, and the order and orientation of regulatory motifs, to accurately describe overall <i>cis</i>-regulatory structure. In our work we present an improved computational method that builds a feature collection based on all of these structural features. We demonstrate the utility of this approach by modeling the <i>cis</i>-regulatory modules of antenna-expressed genes in <i>Drosophila melanogaster</i>. Six potential antenna-related motifs were predicted initially, including three that appeared to be novel. A feature set was created with the predicted motifs, where a correlation-based filter was used to remove irrelevant features, and a genetic algorithm was designed to optimize the feature set. Finally, a set of eight highly informative structural features was obtained for the RRs of antenna-expressed genes, achieving an area under the curve of 0.841. We used these features to score all <i>D. melanogaster</i> RRs for potentially unknown antenna-expressed genes sharing a similar regulatory structure. Validation of our predictions with an independent RNA sequencing dataset showed that 76.7% of genes with high scoring RRs were expressed in antenna. In addition, we found that the structural features we identified are highly conserved in RRs of orthologs in other <i>Drosophila</i> sibling species. This approach to identify tissue-specific regulatory structures showed comparable performance to previous approaches, but also uncovered additional interesting features because it also considered the order and orientation of motifs.</p></div

Conservation of SFs between the RR of <i>D. melanogaster ac</i> and the RRs of orthologs across the <i>Drosophila</i> lineage.

<p>The colored squares represent the antenna-related motifs. Squares on or under the black line indicate motifs on the plus or minus strand, respectively. The red cross means either that the respective region does not contain conserved features or that there is no such ortholog. The phylogenetic tree is based on the tree reported in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104342#pone.0104342-Stark1" target="_blank">[46]</a>.</p

Performance of our GA with two different sets of co-expressed genes.

<p>The red line represents the AUC for antenna-expressed genes in <i>D. melanogaster</i>, and the blue line represents the AUC for muscle-expressed genes in <i>C. elegans</i>.</p

The set of SFs that best describe the RRs of antenna-expressed genes in <i>D. melanogaster</i>.

<p>For each feature, the relationship between motifs within the feature and the Kullback-Leibler weight are shown. The colored squares represent the antenna-related motifs. Squares on or under the black line indicate motifs on the plus or minus strand, whereas squares in the middle of the black line indicate motifs on either strand.</p

Workflow of our computational method.

<p>Workflow of our computational method.</p

Schematic of our upstream RR-scanning approach.

<p>The same approach was followed for the downstream regions. The geometrical forms on and under the black line represent the TFBS on the plus and minus strand, respectively. The orange and green lines and the rectangle indicate the computed SFs.</p

Detailed architecture of four of the highest-scoring <i>D. melanogaster</i> RRs.

<p>Each ‘F’ represents a SF. The human gene names are shown for the <i>D. melanogaster</i> genes with human orthologs.</p

Additional file 6: of Genome-wide map of RNA degradation kinetics patterns in dendritic cells after LPS stimulation facilitates identification of primary sequence and secondary structure motifs in mRNAs

Multiple alignment of sequences found with each motif. Sequences found by searching with the motifs were aligned by Infernal and shown in Stockholm format. Refseq ID of the origin of the sequence, positions of the 3′ UTR in the mRNAs of the Refseq ID, and positions of the sequence found by motif searching was shown in the left column. Common secondary structure (SS_cons) and consensus sequence (RF) are also shown. (PDF 214 kb