Tutorial

Biertool is the new interface for the variant prioritization tool.

This section explains how to use main tasks for Biertool.

On the right top of home page, there are two buttons Login and Sign up, and a help option that contains: documentation and tutorial.

biertool_login

After logging in, other options can be visualized on the top of main page.

biertool_home

To create a new account in Biertool, you only have to click sign in. It will appear a new window where you can select new account and fill in some fields. It is free. Once your account is created you can log in into a private session. All the files you upload will be saved there and will appear in the next session.
We'll see the different functionalities of the tool.

Loading Files

From Study Browser you can:

Create a Project
Create a Study: You can choose the study type: Family, Case/Control, Paired... Each study type will has different priorization options (filters) in Variant Browser. Only in Family study type it's posible manage and connect families.
Upload Files: The input is a VCF file: individual VCF file for only one sample or multisample VCF file for several samples (families or group of cases /controls).

biertool_upload

You must click in Upload button and a new window will open. You can choose a VCF file and wait to finish the validation. If there is no errors in your file,then you can click in Upload and the VCF will load and begin automatic indexing. If there are one or more errors can not load the file, you must correct the errors shown in errors tab. If there is more than hundred errors, validation is stopped automatically. There is also a stop button and a revalidate button.

biertool_indexing

Select Samples or Connect and select a family

After uploading VCF file, you have two options:

You can select one or more samples, in Samples tab, from one or more VCF in READY status to see them in Variant Browser.

biertool_select_samples

You can select a family, in Family tab, to see it in Variant Browser. If you double click in the family, you can view the family tree preview.

biertool_select_family

For Create a Family you must select one or more Samples from one or more VCF in READY status and click in Connect Family:

biertool_connect_family

You can manage the family and preview conections in a Family Tree. When the family is conected, you can save it and then the family is saved in Families tab.

biertool_manage_family

Variant Browser

After select samples or a family, you can see them in Variant Browser. On the left top of the page you can find three buttons: Filters History: Save the last twenty filters used. Clear: Clean filter form. Search: Apply the filters that are now in the form.

Under the buttons, on the left, you can see the filter form that contains all the Biertool filters. They will be explained in the next section of this tutorial.

On the right, there are all the variants found by your filters. If you select a row in this table, you can view the Variant Data below, that will be explained in following sections.

biertool_variant_browser

This is a general first view of detected variants. Next step for each user is defining his own strategy of filtering according to his interests.

Filtering options

There are several filters to define the best strategy of variant selection. It is possible to choose one or more of several filtering options at the same time:

Inheritance: (Only it is shown in Family studies) This intuitive filter that allows reproducing any familiar pedigree with any inheritance model. Also case-control or sporadic de novo mutational diseases can be analysed in this framework. Biertool also manages efficiently missing values (by default Biertool shows variants with 0 missing values for genotypes, but you can modify this parameter). We only have to select the possible genotypes for each sample.

If you are working with a conected family, you can choose the type of inheritance (dominant, recessive, linked to X or linked to Y) and the genotypes are selected automatically, although you can change this options if you think that it is wrong.

biertool_inheritance

Somatic: (Only it is shown in Paried studies) You can choose Somatic or Germinal samples and search intersection.

biertool_somatic

Position:

biertool_position

Region: Several possibilities to define a region: - Only one chromosomal region: 1:1-10000000
- Several regions (separated by comma): 1:1-10000000, 2:1-10000000
- Some chromosomes(separated by comma): 4,5,8
Gene: Only variants for a group of genes. Example: BRCA2,PPL (separated by comma). Also you can manage genes in Gene Panel Browser.

biertool_gene

SNPId: Example: rs9988179,rs140361978 (separated by comma)

Type: SNV, INDEL, CNV, MNV, SV

biertool_type

Population frequencies: This filter is based on known population frequencies, including several subpopulations:

1000 Genomes Phase 3: 1000 Genomes
ESP 6500: Exome Variant Server
ExAC: [Exome Aggregation Consortium] (http://exac.broadinstitute.org/)

biertool_population

Protein substitution scores:

biertool_scores

Conservation: Set pathogenicity thresholds.

PhastCons is a program for identifying evolutionarily conserved elements in a multiple alignment, given a phylogenetic tree.
PhyloP scores measure evolutionary conservation at individual alignment sites

biertool_conservation

Consequence types: Effect. Selecting one or multiple consequence type. It is possible uncheck or selecting several effects at the same time. The terms are sorted by the [IMPACT] (http://www.ensembl.org/Help/Glossary?id=535) rating of the severity of the variant consequence (high, moderate, low or modifier).

biertool_CT