VARPIN - Variant Prioritization and Interpretation for Genetic Analysis

User Guide

How it works

VARPIN is variant prioritization software using a ranking methodology based on ANNOVAR returned data. It capable of processing large datasets and also provides additional information for the variant that matched with ACMG recommendation data.


Demo

In case the user needs to try VARPIN, Demo has been provided to serve as a program demonstration.

  • Demo Input File: User can download demo input file and submit in the submission page to understand the workflow of the program.
  • Demo Report Page: The preprocessed report page of the demo input file to demonstrate the result of the program.


Usage

The following instruction is how to submit a record to VARPIN. There are 2 different ways a user can choose from.

Express Method

This method required minimal data to be submitted. Suitable for a user who already has a setting file or wishes to calculate the input file with the default setting.

On the main webpage of the website. Specify the following data to VARPIN:

The following data is mandatory.
  • Input VCF File : Select VCF file that contains variant informations
  • Record Name : Name of the record
The following data is optional.
  • Setting File : A file that contains a custom variable value. This file can be generated from the setting generator or download from the submitted record. In case the user did not specify a setting file, the system will use the default setting to calculate the submitted file.
  • Email-Address : Email Address for receiving notification and new access key of the record. In case no Email Address has been specified, the user will have to save the Access Key of the record manually and the record will unable to reset the Access Key.

Then click "UPLOAD" button to submit the record.

Advance Method

This method provides more control over the calculation setting of the submitted record for the user.

  1. Click the "Advanced Setting" button on the main webpage of the website.
  2. The user will be presented with an advanced setting page in which the database, the group can be selected to use in the calculation and variable value can be assigned.

  3. On the first page is the General Information Page. Specify the following data to VARPIN:

    The following data is mandatory.
    • Input VCF File : Select VCF file that contains variant informations
    • Record Name : Name of the record
    The following data is optional.
    • Email-Address : Email Address for receiving notification and new access key of the record. In case no Email Address has been specified, the user will have to save the Access Key of the record manually and the record will unable to reset the Access Key.

    Then click "Next >" button to go to Database Selection page.

  4. The Second page is Database Selection Page. Users can select a database that users wish to use in the variant calculation process.

    After the selection, click "Next >" Button to go to Display Only Selection page.

  5. The third page is the Display Only Selection Page. Users will be able to choose a database from the previous page that will not affect the scoring and filtering process but will display information from the database in the report file.

    After the selection, click "Next >" Button to go to Variable page.

  6. The last page is Variable Page. where the value of the variable that will be used in the calculation can be specified.

    • Skip this part : When clicking this button, users will be sent to the upload button positioned at the bottom of the page.
    • Use default value : When the checkbox is checked, the system will use the default value of the current variable in the calculation.

    After database selection, click the "upload" button to submit the record.


After Submit

After the record has been submitted. The user can access the record by using Access Key obtained from the history page or Email Address that the user has provided.

  1. In case the record is still in the processing queue, the user will be redirected to the record status page.
  2. In case the record has finished processing, the user will be redirected to the report page.
Record Status

This page will be shown if the user accesses the record when it is still processing. Display the current status of the record.

Report Page

This page will be shown if the user accesses the record when the calculation has been done. Display choices of report downloading or record management. The record will be automatically deleted after the expiration time of the record.

  • Download : Use buttons in this section to generate a report of the record.
  • Menu : Use the following menu to manage the record
    • Download Setting File : Click this button to download the setting file which contains variable values that have been used in the calculation of the record.
    • Delete : Click this button to delete the record before its expiration time.

Default Setting List

Here is the default variable value that will be used in the calculation in case of custom setting did not specified.

Group Variable
Group Name Variable Name Description Value
filter_score mode Filtering mode of this group 1 + Remove varaint if Benign and not be a splicing site in regsnpintron.
Database Variable
Database Name Variable Name Description Value
func_refgene filter_list (No Value) exonic, splicing, ncRNA_exonic, ncRNA_intronic, ncRNA_splicing, intronic
mode 0: filtered if in filter_list | 1: filtered if not in filter_list Keep variant if matched with filter_list
exonic_refgene filter_list (No Value) synonymous SNV, unknown
mode 0: filtered if in filter_list | 1: filtered if not in filter_list REMOVE variant if matched with filter_list
aachange gene_name_list Gene name that you wish to find (1 line per gene name) (No Value)
refseq_list Refseq accession number that you wish to find (1 line per number) (No Value)
exon_list Exon name that you wish to find (1 line per exon name) (No Value)
coding_ref_list Coding DNA reference sequence that you wish to find (1 line per refseq) (No Value)
protein_ref_list Protein reference sequence that you wish to find (1 line per refseq) (No Value)
exonic_refgene_score list Determine which exonic function prefered to be seen first in the report. frameshift insertion, frameshift deletion, frameshift substitution, stopgain, stoploss
1000g threshold Specified threshold to distinguish data between common and uncommon (Min: 0 / Max: 1) 0.05
exac threshold Specified threshold to distinguish data between common and uncommon (Min: 0 / Max: 1) 0.05
esp6500 threshold Specified threshold to distinguish data between common and uncommon (Min: 0 / Max: 1) 0.05
gnomad_exome threshold Specified threshold to distinguish data between common and uncommon (Min: 0 / Max: 1) 0.05
gnomad_genome threshold Specified threshold to distinguish data between common and uncommon (Min: 0 / Max: 1) 0.05
revel weight Weight of this database 1.9262
sift weight Weight of this database 0.9924
polyphen2_hdiv weight Weight of this database 0.9228
polyphen2_hvar weight Weight of this database 1.0794
mutation_taster weight Weight of this database 1.664
mutation_assessor weight Weight of this database 1.1849
vest3 weight Weight of this database 1.4583
lrt weight Weight of this database 0.958
metasvm weight Weight of this database 1.0051
metalr weight Weight of this database 1.0468
cadd weight Weight of this database 1.0301
dann weight Weight of this database 0.964
fathmm_mkl weight Weight of this database 0.921
gerp weight Weight of this database 0.997
fathmm weight Weight of this database 1.3344
provean weight Weight of this database 1.1105
phastcons20way weight Weight of this database 0.9393
phastcons100way weight Weight of this database 1.0137
siphy weight Weight of this database 0.9098
regsnpintron_disease disease_mode Mode of scoring 0/0.5/1 (Benign/Possibly Damaging/Damaging)
dbsc_snv_ada threshold_ada Specified threshold to distinguish data between benign and deleterious (ADA Score Only) (Min: 0 / Max: 1) 0.6
dbsc_snv_rf threshold_rf Specified threshold to distinguish data between benign and deleterious (RF Score Only) (Min: 0 / Max: 1) 0.6

Contact

If you found any problem persist in the system or would like to report a bug. Please contact: pitinat.asa@mahidol.ac.th