Tutorial

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Query Input:

1. Select Query Type:
   • Search for genetic functionalogs for a gene: Returns the relevant section of the genetic (siRNA+miRNA) cluster (Supplemental Figure 2A) for display of cluster-based relationships together with rank-ordered nearest neighbors of the query gene based on the selected distance or correlation metric.
   
   
   • Search for chemical functionalogs for a gene: Returns a rank-ordered list of nearest neighbor natural product fractions based on the selected distance or correlation metric.
   
   
   • Compare a pair of genes for their functional similarity: Returns the user-selected distance or correlation between a gene pair.
     • Input: Requires one gene pair separated by a comma and/or whitespace.
       (e.g. “AKT1, AKT2”)


2. Select a distance or correlation metric from the indicated drop-down menu:
   • Euclidean distance sum (default)
   • Mahalanobis distance sum
   • Euclidean distance rank sum
   • Pearson correlation.


3. Select a false discovery rate filter (FDR cutoff) from the drop-down menu:
   • TOP 100 (default): 100 functionalogs with the lowest p value.
   • GET ALL: No filter (only available if APC is matched).
   • FDR<0.1
   • FDR<0.2
   • FDR<0.3
   • FDR<0.4
   • FDR<0.5


4. Select checkbox to return functionalogs that match the queried gene's cluster number determined by Affinity Propagation Clustering (APC) algorithm. APC is only available for metrics:
   • Euclidean distance sum (default)
   • Pearson correlation


5. Input the gene or miRNA symbol of interest.
   • Only 1 symbol for functionalog search and 2 for comparison.
   • Input requires an appropriate HUGO gene symbol (case insensitive).
   • A list of currently queryable gene symbols is here.

Output Description:

1. Associated Subcluster: Heatmap of the subcluster associated with gene of interest. Derived from clustering the complete kinome+miRNA dataset.
2. Symbol: Gene symbol or name of the natural product.
3. Metric: Sum of triplicate measures (Dist1, Dist2, Dist3).
   • Distsum: Euclidean distance sum
   • Mahalanobis: Mahalanobis distance sum
   • Ranksum: Euclidean distance rank sum
   • Pearson: Pearson correlation
4. P-value & FDR: Obtained from permuted dataset. FDR value is displayed only when it is less than 0.5. See Supplemental Methods for details.
5. APC: Cluster number is determined by the apcluster R package using the specified distance metric.
6. BNIP3L, NDRG1, ALDOC, LOXL2, BNIP3, ACSL5: LOG₂ transformed normalized gene expression values for each of the 6 reporter genes.

Output Management

1. Query Parameters: Displays search parameters for the current query results.
2. Output Options
   • Distance Table: Download CSV file containing the distance table (Symbol, Metric, Dist1-3, P value, FDR, APC).
     Queried gene data is NOT included.
   • Expression Table: Download CSV file containing Log₂ expression values of functionalogs.
     Queried gene expression is included.
   • Cluster Expression: Hierarchically cluster the Log₂ expression results from the current query. Get PDF file.
3. Display Options
   • Expression Heat Map: Collapse gene expression numeric values for quick comparisons.
   • Heatmap Data Box: Display text box in lower left corner to display heatmap cell data.
   • Persistent Row: Always display queried gene row as you scroll down.
   • Associated Subcluster: Display all images of subclusters associated with the gene of interest.