Archigene Browser

Archigene Browser is a complete genome viewer
In order to benefit from a better user experience, it is recommended to use Chrome, Firefox or Opera as a browser.


The browser consists of 2 parts, the overview at the top and the tracks below.
In order to be able to move in the genome, there are 2 possibilities:

Using the mouse
The zoom in and out are done through the wheel, the zoom is then on the genomic position of the mouse. Lateral and vertical displacement is done by keeping the left click and moving the mouse. The movement stops when the left click is released.

Using the keyboard
The arrows "up" and "down" of the keyboard allow to zoom, the arrows "left" and "right" lateral movements.


Overview

The overview represents the position of the view of the tracks relative to the chromosome or to a transcript.
It is possible to position the browser directly on a cytogenetic band by clicking on it.
When a gene is selected, the overview then shows the gene transcript. It is then possible to position the browser on an exon by clicking on the rectangle displaying the exon number at the bottom of it.


Tracks

The tracks are below the overview and are on top of each other.
It is possible to move a track using the buttons and located to the left of the title.
The button allows you to fold and unfold the track.
The button located to the right of the track allows to remove it from the view.

To be able to add a track, you have to open the window for adding a track using the menu "Navigator → Add track" or the button located at the bottom left of the piste view.
The Add Track window displays all available tracks.


Genome

The genome track displays the reference genome in the forward direction on the top line and in the reverse direction on the bottom line. The genomic coordinates are displayed at the top of the track according to the HGVS recommendations.
The track title displays the genomic coordinates of the window being viewed.

The selection of a sequence of the reference genome is done on the forward strand at the top of the track by clicking on a nucleotide. The sequence being selected is then surrounded by a green rectangle.

A context menu is available by right clicking on the selected area and allows you to perform the following actions:

  • Create a variant
  • Create an annotation
  • Copy the selected genomic sequence
  • Copy genomic positions


Nucleotidic conservation

The nucleotide conservation track represents Phylop data from the UCSC. Each genomic position has a score represented by a blue rectangle.
A tooltip allows to display the score of the position under the mouse.


Genes

The gene track makes it possible to visualize all the genes and their transcripts. The exons are represented in green and the introns in gray. The blue arrow next to the name of the gene indicates the direction of transcription. When the exon is coding, it contains the amino acid sequence of the transcript.
Coordinates in c. are represented above the transcript and the coordinates p. below according to HGVS recommendations.
A tooltip displays the coordinates in g., p. and c. a position on the exon of the transcript.
The START codon of the transcript is blue and the STOP codon is red. The selection of a transcript is done by clicking on the zone below. The green dot on the title of the transcript then indicates that the transcript is selected. The overview displays the details of the transcript. Selecting a transcript displays the data related to it on the following tracks:

  • Splice sites
  • Splicing regulation
  • Orthologs
A new menu dedicated to the gene appears in the menu at the top. This menu allows you to change the transcript and visualize the gene data in the PUBMED and LOVD sources.


Public variants

A new menu dedicated to the gene appears in the menu at the top. This menu allows you to change the transcript and visualize the gene data in the PUBMED and LOVD sources.

  • dbSNP
  • Clinvar
  • GnomAD
  • 1000Genomes
  • HGVD
  • GoNL
  • ESP
For more information, consult the sources of data available in the application. The substitutions are shown at the top of the track, the alternative allele of the variant is displayed in the rectangle corresponding to the genomic position.
Insertions are represented by triangles below substitutions.
The deletions and delins are represented at the bottom of the track by a rectangle of length identical to the deleted sequence. Variant color is taken from Clinvar using the classification provided by this data source.
A tooltip is available on each variant and allows to display information on the variant in the different sources where it is present.


Private variants

The Private Variants Track allows you to display your own variants.
Variants are displayed as on the public variants track.
The color of the variant indicates the classification that has been given by the variant. A tooltip is used to display the variant's name and the date it was created and last updated on your Archigene user account. A context menu is available by right-clicking a variant and displays the variant in the variant window.


Team variants

The Team Variants Track shows variants that have been saved to your Archigene user account.
The color indicates the highest rating published by a member of your team for that variant.
You must enable variant sharing in your settings in order to be able to publish variants in your team.


CNV

The CNV track displays the structural variants of DGV and gnomAD. A tooltip allows you to display information from DGV and gnomAD on the CNV.


Private CNV

The Private CNV Track allows you to display your own CNV.
Variants are displayed as on the public CNV track.
The color of the variant indicates the classification that has been given by the CNV. A tooltip is used to display the CNV details. A context menu is available by right-clicking a CNV to open the CNV window.


Splice sites

The track displays the donor and acceptor splice sites for a transcript. You need to have a transcript selected to display this data (see Genes ).
The sites at the top of the runway are splice sites predicted by the MaxEntScan, NNSplice and SSF tools. The height of the chip represents the strength of the splice site, the score is the combination of the 3 predictors.
The splice sites at the bottom correspond to the natural sites on the gene for all the transcripts of the gene. At each splice site it is possible to display a tooltip which gives the values ​​of the predictors. The range of values ​​for each predictor is as follows:

  • MaxEntScan between -50 and +20
  • NNSplice between 0 and 1
  • SSF between 0 and 100


Splicing regulation


Orthologs

The Orthologs Track shows orthologous alignments on several species for a transcript. You need to have a transcript selected to display this data (see Genes ).
The orthologs of the gene are from Ensembl and aligned with MUSCLE with the transcript. The top 10 alignments are displayed at the bottom of the track. The differences with the reference transcript are displayed in orange.
Each line corresponds to a species, the name of the species is displayed on the left.
At the top of the trail are conservation on all species of orthologues of Ensembl. The height of the blue rectangle corresponds to the conservation score of the AA on the position. A tooltip is available on the holdings and allows to display in detail the information on a position.


Secondary structures

The track displays the data of the secondary structures of the selected transcript. The data represents the HELIX, BETA STRAND and TURN structures of the PDB files corresponding to the transcript. Alignment is performed by UniProt A tooltip displays information about the structure. The secondary structures predicted by Spider3 are above the transcript and those observed are below.


Private annotations


Team annotations

The Private Annotations Track allows you to display the annotations recorded in your team.
You must enable annotation sharing in your settings in order to be able to publish annotations in your team.


Repeat Masker

The Repeat Masker track screens DNA sequences for interspersed repeats and low complexity DNA sequences. This track displays up to ten different classes of repeats:

  • Short interspersed nuclear elements (SINE), which include ALUs
  • Long interspersed nuclear elements (LINE)
  • Long terminal repeat elements (LTR), which include retroposons
  • DNA repeat elements (DNA)
  • Simple repeats (micro-satellites)
  • Low complexity repeats
  • Satellite repeats
  • RNA repeats (including RNA, tRNA, rRNA, snRNA, scRNA, srpRNA)
  • Other repeats, which includes class RC (Rolling Circle)
  • Unknown
A tooltip is available on the annotations and allows you to display detailed information on a region.


Variants


Creation

The creation of a variant is done directly on the track of the reference genome by selecting with the mouse the sequence in the forward direction The selected sequence will appear surrounded by a green rectangle.
By right-clicking on this area, a pop-up menu appears and displays the variant creation window.
The variant creation window displays the starting genomic position of the selection as well as the non-modifiable reference genome selected previously. In the "Alt" field, you must enter the alternative sequence.
In order to be able to create an insertion, it is necessary to check the Insert box at the bottom of the window, the reference sequence is empty.
By clicking on the "Create" button, the creation window disappears and the variant window appears.

It is also possible to create a variant directly by entering the gNomen of it in the search bar at the top of the application.


Details

The variants window displays the data of a genomic variant on the right of the screen.
The window is broken down into several parts:

  • General description
  • List of transcripts
  • Detail for a transcript
  • Splicing
  • Public variants
  • Predictions
  • Personal informations
The list of transcripts is used to display the general information about the variant for all the transcripts of the Archigene database. affected by the variation. The information is as follows:
  • the name of the gene
  • the name of the transcript
  • the nomenclature in c. Variant according to HGVS recommendations
  • the nomenclature on p. Variant according to HGVS recommendations
  • the location of the variant on the transcript
  • the list of the consequences of the variant on the transcript
  • the impact of the variant on the transcript
This list allows you to select a transcript for displaying additional information about the transcript in the section below.
The selected transcript appears in a different color on the transcript table line.

The detail of a transcript for the variant contains the following parts:
  • General information on the gene
  • General information about the transcript
  • HGVS nomenclatures
  • Impact
  • Location
  • Amino acid changes


The ACMG Guidelines provide a suggested classification of the variant according to the pre-calculated criteria below:
  • PVS1 : Null variant (nonsense, frameshift, canonical ±1 or 2 splice sites or initiation codon)
  • PS1 : Same amino acid change as a previously established pathogenic variant in Clinvar
  • PM2 : Absent from gnomAD or at extremely low frequency
  • PM4 : Protein length changes as a result of in-frame deletions/insertions or stop-loss variant
  • PM5 : Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before in Clinvar
  • BA1 : Allele frequency is >5% in gnomAD
  • BP6 : Clinvar reports variant as benign
  • BP7 : A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus
By clicking on the criteria displayed on the left, the detail of this one then appears on the right part.


The splicing information includes a variant impact calculation part on the splicing of the area according to the MaxEntScan, SSF and NNSplice predictors.
A graphic area displays the splice sites on the reference sequence and the sequence mutated by the variant. The donor sites are represented in blue and acceptor sites in green. The height of the stick represents the strength of the splice site according to the predictors MaxEntScan, SSF and NNSplice.
SpliceAI: A deep learning-based tool to identify splice variants
The SpliceAI predictions are directly computed and therefore available for all variants in hg19 and hg38.
The largest changes in the nearest acceptor and donor sites are displayed in a table. The scores of all the sites near the variant are displayed in the graph below. The donor sites are represented in blue and acceptor sites in green. The height of the stick represents the strength of the splice site according to SpliceAI.
SpliceAI must be activated in your personal settings to be displayed.

The different information about the presence of the variant in the different databases is displayed in the section public variants. The information for each data source is in a map. When the variant is present, the left border of the map is colored blue. In some maps, a link to the data source site is located at the top right of the data source.
Predictor information is displayed in the Predictions section. Some predictors are only displayed when the variant is a missense on the transcript. Here is the list:
  • Polyphen-2 (The data is WHESS.db and is requested by HTTPS when opening the window)
  • SIFT
  • AlignGVGD
The list of predictors based on genomic information are as follows:
  • CADD
  • DANN
  • FATHMM


Manage

When you are logged in with your Archigene account, you have the option of saving variants with the following information:

  • Classification with a drop-down list
  • A comment in a free text field
  • The phenotype in a free text field
A button at the bottom left of the variant window allows you to save the variant.
The saved variants are then visible on the private variants track. When a variant is saved, a "Delete" button is available in the variants window. Attention, the suppression of a variant is not reversible, all information of the variant will be lost. Private variants are stored in 2 modes:
  • Archigene Servers: Variants are saved on Archigene servers. Your variants are not public and are only visible with your account.
  • Local: Variants are saved locally in your browser on your computer. Warning, deleting your browser will result in the loss of your data.
The configuration of the information storage mode is available in the settings window of your account.


CNV


Creation

The creation of a CNV is done directly on the track of the reference genome by selecting with the mouse the sequence in the forward direction The selected sequence will appear surrounded by a green rectangle.
By right-clicking on this area, a pop-up menu appears and displays the cnv creation window.
The CNV creation window displays the starting and ending genomic position of the selection.
By clicking on the "Create" button, the creation window disappears and the CNV window appears.


Details

The CNV window displays the data on the right of the screen.
The window is broken down into several parts:

  • General description
  • List of genes
  • Public CNV
  • Personal informations
The list of genes is used to display information on the genes that are impacted by the CNV. The information is as follows:
  • the name of the gene
  • Gene Id
  • HGNC Id
  • the description of the gene
  • The strand of the gene
The public CNV list is used to display the public CNV of DGV and gnomad that overlap the CNV. The information is as follows:
  • The Source
  • Genomic start
  • Genomic end
  • CNV Type
  • Details (Publication for DGV and frequencies for gnomAD)
  • Impacted genes (genes similar to cnv are shown in bold)


Manage

When you are logged in with your Archigene account, you have the option of saving CNVs with the following information:

  • Classification with a drop-down list
  • A comment in a free text field
  • The phenotype in a free text field
A button at the bottom left of the CNV window allows you to save the CNV.
The saved CNVs are then visible on the private variants track. When a CNV is saved, a "Delete" button is available in the CNV window. Attention, the suppression of a CNV is not reversible, all information of the CNV will be lost. Private variants are stored in 2 modes:
  • Archigene Servers: CNVs are saved on Archigene servers. Your variants are not public and are only visible with your account.
  • Local: CNVs are saved locally in your browser on your computer. Warning, deleting your browser will result in the loss of your data.
The configuration of the information storage mode is available in the settings window of your account.


User account

To have an Archigene user account, you must register with the registration button at the top right of the navigation bar.
When you are logged in to Archigene Browser with your user account, the following features are available:

  • Private variants: You can save, consult the annotations on your private variants in the variants window. Your variants appear in the private variants track.
  • Private annotations: You can save, consult your private annotations.
  • The mode of storage of private variants and private annotations
  • The choice of a transcript on the gene track is automatically saved to your account.
  • Tracks and track order are automatically saved to your account.
  • The language of the interface


Direct access


The search bar at the top left of the application provides direct access to certain information:

Variant
  • <assembly>:<chromosome>:<gNomen> Création d'un variant

  • <assembly>:<transcript>:<cNomen> Création d'un variant

On a chromosome being viewed, it is not necessary to complete the assembly and chromosome fields.
If a transcript is selected, the cNomen can be searched directly.


Position
  • <assembly>:<chromosome>:<position> Access to a genomic position

On a chromosome being viewed, it is not necessary to complete the assembly and chromosome fields.


An url allows you to directly access information using GET parameters: https://www.archigene.com/browser/search.php

Chromosome
hg19:22

Variant
g.19455397C>G


Files

Archigene Browser allows you to view the contents of different files in VCF, BED and GFF formats directly on the open chromosome.


VCF

To be able to view the contents of a VCF file, select the "Files → Load VCF file" menu at the top of the browser.
Once the VCF file is selected, a track with the name of the VCF file will be added to the list of tracks currently being viewed.
This track will display the variants of the VCF file available on the open chromosome.
Variants are organized in the same way as the variant track.

A tooltip makes it possible to display on each variant the detail of this one contained in the file VCF.


BED

To be able to view the contents of a BED file, you have to select the "Files → Load a BED file" menu at the top of the browser.
Once the BED file has been selected, a track with the name of the BED file will be added to the list of tracks being viewed.
This track will display the annotations contained in the BED file available on the open chromosome. An arrow indicates the direction of the annotation

A tooltip allows to display on each annotation the detail of this one contained in the file BED.


GFF

To be able to view the contents of a GFF file, you have to select the "Files → Load GFF file" menu at the top of the browser.
Once the GFF file is selected, a track with the name of the GFF file will be added to the list of tracks being viewed.
This track will display the annotations contained in the GFF file available on the open chromosome. An arrow indicates the direction of the annotation.

A tooltip makes it possible to display on each annotation the detail of this one contained in the file GFF.


BAM (alpha)

The visualization of BAM files is still in Alpha version, the features are limited. To be able to display the contents of a BAM file, you have to select the "Files → Load a BAM file" menu at the top of the browser.
You must open the BAM file and the .bai index file.
This track will display the information contained in the BAM file available on the open chromosome.
Each read is represented by a rectangle, the color indicates the direction of the read.