PMC

ClusterScout. (A) User Interface with algorithm logic schematic. (B) The results from a ClusterScout search are presented in a table, and custom BCs can be added to the BC Cart for analysis.

Similarity Search (A) BC similarity search is accessible through the ‘Similar Clusters’ tab (i) in the Biosynthetic Cluster Detail page, in this case the streptomycin BC from Streptomyces griseus. (B) The results are presented as a table which includes the ‘Jaccard Score’ and the ‘Adjusted Jaccard Score’. As expected, two more experimentally verified BCs known to produce streptomycin are retrieved, in addition to multiple predicted BCs. Users can further analyze these BCs by (i) adding them to the BC Cart, or (ii) visualize the neighborhoods of selected BCs to compare them with the query BCs.

IMG-ABC case study. (A) The BC Cart is the virtual space where BC analysis can be performed. (B) The function heatmap visualization can be used to study the Pfam content of BCs. Cells are colored with hues of green based on the number of copies of the selected Pfam in the BC (darker signifies a higher copy number). Hovering the mouse pointer over a cell provides the number of copies of that Pfam in the BC. Pfams (columns) that occur in all BCs (rows) likely define the core functions of the BCs in view. Column and row metadata are found on top and to the right, respectively, of the heatmap. Hovering the mouse pointer over these metadata cells provides more detail information. These metadata can be used for quick visual inspection and identification of patterns. For example, betaproteobacteria containing the DAPG BC are easily discoverable (asterisk). (C) The similarity network graph provides another way to summarize the data. The BCs in this example fall into three distinct groups; two groups contain gammaproteobacteria (red nodes) while one group consists of betaproteobacteria (purple nodes). The green node represents experimentally verified BC for DAPG (from a gammaproteobacterium Pseudomonas fluorescens) in the IMG-ABC database. Clicking on a node reveals the metadata associated with the BC (table on the right). The color of the nodes can be changed to display different metadata, such as taxonomic classification or evidence. (D) Visualization of the putative DAPG BC neighborhoods from the four betaproteobacterial BCs and one BC from each gammaproteobacterial group shows that although the flanking regions of the BCs differ, the core genes are conserved, thus it is likely that these newly discovered BCs indeed encode the necessary proteins for DAPG production.