1. [Run wKDA] from MSEA: Part 10a will start the Weighted Key Driver Analysis pipeline for the list of significant merged-supersets in the "Merged supersets" table (see Merged Supersets). wKDA takes a gene set as input and searchs for genes in a network whose neighborhoods are enriched for genes in the input gene set.

1. Enter wKDA Parameters

1. Enter wKDA Search Depth: used to define a candidate key driver's local network neighborhood by considering genes at a given distance or depth
   Options: 1/2/3. It indicates the maximum edge distance starting from each candidate key driver gene.
   Default Value: 1
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2. Enter wKDA Edge Type: defines whether the directionality of edges is considered.
   Options: Incoming and Outgoing/Only Outgoing. The former ignores directionality and the latter considers directionality by requiring the candidate key driver to be upstream of its local neighborhood genes
   Default Value: Incoming and Outgoing
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3. Enter wKDA Min Overlap: Used as threshold for gene overlaps to group hubs as co-hubs.
   Options: Between 0-1. The higher the value, the more the local network neighborhood of hubs must overlap to be considered co-hubs.
   Default Value: 0.33
4. Enter wKDA Edge Factor: Used to weight edge info of network to the power of the value entered
   Options: Between 0-1. A power of zero would set all the edge weights to be equal (1).
   Default Value: 0.5
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1. Select/Upload Network

1. Select/Upload Network Menu gives the user sample network datasets. The description for the sample network datasets is included in Table 1. The first option in the menu is for uploading your own network. The input file format is described in Table 1. Included are a number of tissue-specific bayesian networks and a PPI network.
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• TAIL	HEAD	WEIGHT
  A1BG	SNHG6	1
  A1BG	UNC84A	1
  A1CF	KIAA1958	1

1. Enter Email and Submit Job

1. Enter your Email ID in the text box and press submit (Optional) if you prefer to get notification emails regarding job start and job completion. The job completion alert will also give you a link for you to download your results. We will delete your e-mail id after job completion and this e-mail id will not be used for any further communication.
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2. Job Execution

1. Your job execution may take 30 minutes or more. This page will load your wKDA results after execution is done. If you want to close this browser then please copy the link in this page to see your results. If you have provided your e-mail id then we will send you this link in your job completion e-mail alert.
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1. Display wKDA Results

1. wKDA Results Table lists the key drivers (second column) in the merged supersets (first column) with the associated p-values and FDRs.
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2. Interpretation of Results

Field Name	Description
Merge Module ID	New module id/gene set after merge
Module Description	Functional description of the merged module
Key Driver Node	Key driver genes in the merged module
P-value	Enrichment p-value for key driver genes
FDR	False discovery rate for the enrichment value of the key driver node
Module Genes	Total number of nodes in the gene module
KD Subnetwork Genes	Number of neighboring nodes for the key driver genes
Module and Subnetwork Overlap	Number of GWAS loci present within the neighbors of the key driver
Fold Enrichment	Enrichment of KD subnetwork genes within the gene module

3. Display Network Graph

1. To display the network graphs for the top key drivers, Click on the [Display Network Graph] button
2. See Visualization Section for a tutorial on the network visualization feature.

The user may bypass MSEA and directly run wKDA if gene sets of interest are available and the user wishes to identify potential key drivers of the gene sets. This tutorial provides an overview of using our KDA pipeline available from [Run wKDA] tab. The example screen shots are included for most of the steps.

1. Select/Upload Gene Sets for wKDA

1. In this step, the users upload their own gene set file or select a preuploaded sample file. The gene set file is a tab delimited text file with two fields, MODULE and NODE. MODULE includes module id which is a unique number for all the genes in the gene set. NODE includes gene names. One sample gene set file is available for download at the download section.
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• MODULE	NODE
  7015	Afm
  7015	Alkbh2
  7015	Art3

2. Enter wKDA Parameters

1. From this step onward follow the steps from Parameters for wKDA in MSEA to wKDA.