Latest DECIPHER news

2019 Curating the Clinical Genome Conference

 

Registrationis now open for Curating the Clinical Genome 2019 Conferenceco-hosted by ClinGenand DECIPHER. This conference will be of interest to a wide group of medical genomics researchers, clinicians practising genomic medicine, companies developing solutions for clinical genomics and researchers interested in genomic data sharing. The conference will take place May 29-31 2019 in Washington, DC, USA.

DECIPHER v9.28 Released

 

We released version 9.28 of DECIPHER on the 6th of February, 2019. This release includes minor changes and updates.

DECIPHER Data Centre essential maintenance and at risk times

 

Due to essential Data Centre maintenance, the DECIPHER website should be considered at risk on the following days:

  • Tuesday 30 October 2018
  • Thursday 1 November 2018
  • Monday 5 November 2018

If you require further information please contact decipher@sanger.ac.uk.

We apologise for any inconvenience caused.

DECIPHER v9.26 Released

 

We released version 9.26 of DECIPHER on the 24th of October, 2018. Improvements include:

  • The posterior probability for the January 2018 ClinGen SVI Bayesian classification framework is now displayed on summative assessments. The summative assessment tool supports multidisciplinary teams working to evaluate whether a variant(s) explains the clinical features seen in a patient.
  • In the Genome Browser, the reference allele(s) for dbSNP variants are now displayed in the information popup.

DECIPHER v9.25 Released

 

We released version 9.25 of DECIPHER on the 12th of September, 2018. Improvements include:

  • DECIPHER now incorporates the GRCh38 to GRCh37 UCSC LiftOver tool enabling users to deposit CNV and sequence variants with GRCh38 coordinates. This tool is available when depositing variants individually or via bulk upload.

DECIPHER v9.24 Released

 

We released version 9.24 of DECIPHER on the 18th of July, 2018. Improvements include:

  • The ACMG Pathogenicity Evidence editor is now displayed on the Pathogenicity Evidence tab before ACMG criteria have been selected, increasing accessibility to the editor.

  • It is now possible to add the phenotypes of a monozygous twin, dizygous twin sister or dizygous twin brother to a patient record.

  • The Allele Frequency tab has been reorganised to ensure that the Tolerated Population Variation Calculator is more accessible. This calculator can be used to determine whether a variant observed in the reference sample is too common to cause a given Mendelian disorder of interest.

Essential System Upgrades Wednesday 6 June

 

There will be significant disruption to this service on Wednesday 6 June due toessential system upgrades. It is likely that disruption will extend beyond our usual weekly at-risk period, and the service should be considered at risk for the whole day. We apologise for any inconvenience this may cause.

Update: This work is now complete.

DECIPHER 9.23 Released

 

We released version 9.23 of DECIPHER on the 23rd of May, 2018. Improvements include:

  • The incorporation of the January 2018 ClinGen Sequence Variant Interpretation Working Group (ClinGen SVI) Bayesian classification framework to assist users interpreting ACMG pathogenicity evidence. This framework provides a mathematical foundation for what was a qualitative heuristic.

  • The addition of guidance, when users are recording pathogenicity evidence, from ClinGen SVIon the use of ACMG criteria PP5 and BP6 (reputable source
    criteria). These criteria reply on assertions in the absence of primary evidence.

DECIPHER v9.22 Released

 

We released version 9.22 of DECIPHER on the 25th of April, 2018. Improvements include:

  • Homozygous and Hemizygous gnomAD variants are now displayed on the protein browser. The new tracks allow the visualisation of protein changing and loss of function homozygous and hemizygous gnomAD variants.

  • Images of relevant amino acids are now displayed for missense sequence variants on the Consequence Prediction (VEP) tab in patient records.

  • Input values for cardiac conditions for calculating the maximum tolerated population allele frequency are now displayed in DECIPHER. The Tolerated Population Variation Calculator can be used to determine whether a variant observed in the reference sample is too common to cause a given Mendelian disorder of interest.

  • The DECIPHER pathogencitiy class Definitely pathogenic” has been changed to “Pathogenic” in line with ACMG and ACGS nomenclature.

DECIPHER v9.21 Released

 

We released version 9.21 of DECIPHER on the 7th of March, 2018. Improvements include:

  • Copy number variants are now displayed (and deposited) with a class (deletion, duplication, triplication, duplication/triplication, amplification) and genotype (hemizygous, heterozygous, homozygous). Mean ratio is now an optional field. This allows the context of the copy number variants in a patient to be recognised more easily.
  • A pathogenicity filter has been added to the LSDB track in the genome browser, allowing users to select the pathogenicity of variants they would like to visualise.
  • Matching patients with sequence variants can now be filtered by sex.
  • Phenotypes associated with sequence variants in your gene of interest are now shown in separate tables for pathogenic variants and for pathogenic/uncertain/unclassified variants. This allows users to select which cohort of variants in which they would like to visualise discriminatory phenotypes.

DECIPHER Pre-Release Announcement: Data Deposition Changes

 

In early March there will be some changes to the information required to deposit copy number variants and sequence variants to DECIPHER.

For copy number variants the changes will be:

  • Mean ratio will be optional.
  • Class will be mandatory (deletion, duplication, triplication, duplication/triplication, amplification).
  • Genotype will be mandatory (hemizygous, heterozygous, homozygous, mitochondrial homoplasmy, mitochondrial heteroplasmy).

For sequence variants the changes will be:

  • Genotype will be mandatory (hemizygous, heterozygous, homozygous, mitochondrial homoplasmy, mitochondrial heteroplasmy). This is currently an optional field.

These changes will also affect bulk upload and the templates available to download from the website will be changed accordingly.

If you have any queries or concerns about these changes, please let us know by emailing decipher@sanger.ac.uk.

DECIPHER v9.20 Released

 

We released version 9.20 of DECIPHER on the 24th of January, 2018. Improvements include:

  • All information regarding matching patients can now be filtered by attribute. This allows the most appropriate patient data to be displayed and considered more easily.
  • A list of phenotypes absent in matching patients in now displayed when viewing matching patients in a patient record.
  • Pertinent evidence and links to relevant evidence are now shown for each evidence line when recording ACMG pathogenicity evidence, assisting variant classification.
  • The protein viewer now displays DECIPHER sequence variants mapped onto proteins, alongside other relevant information, for proteins for which no pfam domain information is available.

DECIPHER v9.19 Released

 

We released version 9.19 of DECIPHER on the 29th of November, 2017. Improvements include:

  • Exon boundaries are now shown in the protein browser allowing the position of patient variants in relation to exon structure to be easily identified. Positional information and exon number is provided by clicking on the relevant exon or exon border.
  • Minor Allele Frequency information for combined gnomAD exome and genome data is now available on the annotation tab.
  • A link to Genomics England PanelApp, a crowdsourcing tool from Genomics England which allows gene panels to be shared, downloaded, viewed and evaluated by the scientific community, is now available on the clinical tab.

DECIPHER v9.18 Released

 

We released version 9.18 of DECIPHER on the 4th of October, 2017. Improvements include:

  • Protein browser track settings are now available, allowing users to customise which information is visible on the protein browser. Pathogenicity filters for DECIPHER and ClinVar variants have also been added.
  • DECIPHER and ClinVar variants on the protein browser are now represented as hollow outlines, unless they are annotated as likely pathogenic/definitely pathogenic. This provides the user with an overview of the location of pathogenic variants in their gene of interest.
  • A ClinVar 3 and 4 star review status filter has been added to the genome and protein browsers.
  • The overlapping patient interface now includes a phenotype summary to assist in determining recurrent overlapping phenotypes.
  • Pathogenicity evidence is now shown on a patients summative assessment. The summative assessment tool supports multidisciplinary teams working to evaluate whether a variant(s) explains the clinical features seen in a patient.
  • Matchmaker Exchange search requests now include DDD research variants. The DDD research variants are variants of unknown significance in 4293 children with developmental disorders in the UK DDD study.
  • The diagnosed disorder code (OMIM phenotype MIM code) from openly shared patient summative assessments is now shared over Matchmaker Exchange.

DECIPHER v9.17 Released

 

We released version 9.17 of DECIPHER on the 9th of August, 2017. Improvements include:

  • Minor Allele Frequencies for sequence variants from gnomAD are now shown in the patient sequence variant table. This allows the frequency of the patient variant(s) in the population to easily be viewed.The link to the Minor Allele Frequency can be found in the Annotation column in the sequence variation table in the Genotype tab
  • Minor Allele Frequency information from gnomAD for variants that match the patient variant are now showed on an Annotation tab when viewing the patient record. Consequence prediction (VEP) information can also be viewed on the “Annotation” tab.
    Minor Allele frequency is shown with all subpopulations in gnomAD
  • A tolerated population variation calculator described by Whiffin et al., 2017 is now available in DECIPHER. The calculator allows the determination of whether a variant observed in the reference sample is too common to cause a given Mendelian disorder of interest. The calculator can be accessed from the new Annotation tab when viewing a patient record or by clicking on the exome/genome MAF in the sequence variant table.
    The allele frequency calculator for the LAMA2 variant
  • Missense constraint data can now be viewed on the genome and protein browsers. Missense constraint analysis is based on the ExAC dataset and evaluates how intolerant (“constrained”) a gene or gene region is to missense variants.
    There are four regions within CDK13 which have different missense constraint levels, here shown on a protein view in DECIPHER
  • Within the summative assessment tool, a new very strong level has been created for the evidence line clinical fit. The Summative assessment tool supports multidisciplinary teams working to evaluate whether a variant(s) explains the clinical features seen in a patient.

DECIPHER v9.16 Released

 

We released version 9.16 of DECIPHER on the 26th of July, 2017. Improvements include:

  • Normalisation of patient sequence variants. The same variant can be represented in multiple ways by different systems. Patient variants on the DECIPHER website are now normalised to facilitate the comparison of patient variants with variants from other resources. Variants in DECIPHER are left aligned and parsimonious, as described in Tan et al. 2015.

  • DDD research variants, ClinVar variants and gnomAD variants shown in the genome and protein browsers are normalised using the same method as DECIPHER patient variants, allowing users to more easily identify matching variants.

DECIPHER v9.15 Released

 

We released version 9.15 of DECIPHER on the 31st of May, 2017. Improvements include:

  • gnomAD variant data replaces ExAC data in the genome and protein browsers. The Genome Aggregation Database (gnomAD), contains exome and genome sequencing data spanning 123,136 exomes and 15,496 genomes from unrelated individuals sequenced as part of various disease-specific and population genetic studies. In its first release, which contained exclusively exome data, it was known as the Exome Aggregation Consortium (ExAC).

  • gnomAD coverage data is now shown in the genome browser, allowing users to view sequencing coverage of both exomes and genomes.

  • The Summative Assessment tool, which supports multidisciplinary teams working to evaluate whether a variant(s) explains the clinical features seen in a patient, now has a free text box. This allows additional evidence for the genotype-phenotype relation to be recorded.

  • A legend for CNV colours has been added to the genome browser.

DECIPHER v9.14 Released

 

We released version 9.14 of DECIPHER on the 5th of April, 2017. Improvements include:

  • Additional family members can be created for patients and phenotypes recorded.
  • Manifestations for absent phenotypes can now be recorded, such as the patients age at clinical observation.
  • A pathogenicity filter has been added to the ClinVar track in the genome browser, allowing users to choose to see only pathogenic variants.
  • The amino acid position is now displayed in the pop-up when clicking on an amino acid in the transcript or human sequence in the conservation track.
  • For security reasons, users using Internet Explorer 8 or older can no longer access the DECIPHER website. Users using Internet Explorer versions 9 and 10 can access the site but will be unable to log in. These changes will not affect users accessing our website using Firefox, Chrome, or Internet Explorer 11.

Curating the Clinical Genome meeting 2017

 

The 2017 Curating the Clinical Genome meeting, co-hosted by ClinGen and DECIPHER, will take place in Washington, DC June 28-30, 2017.

Early bird registration deadline is March 31, 2017.

DECIPHER v9.13 Released

 

We released version 9.13 of DECIPHER on the 22nd of February, 2017. Improvements include:

  • A Summative Assessment tool to support multidisciplinary teams working to evaluate whether a variant(s) explains the clinical features seen in a patient. This tool uses a framework to evaluate the Clinical fit and then enables the user to select the OMIM gene-disease pair that best fits the patient and to select possible options to summarize the fit (for example, genetic diagnosis confirmed).

  • ClinVar variants are now shown on the protein browser.

  • A pathogenicity filter has been added to the DECIPHER sequence variant track.

  • The display of ClinVar and dbSNP variants in the genome browser has been improved, allowing the user to more easily identify if multiple variants are located in the same position when zoomed in.

  • The pathogenicity of DECIPHER sequence variants is now shown in the popups on the genome and protein browsers, when a user clicks on the variant.
  • The patient phenotype interface displays icons representative of high-level phenotype terms.

DECIPHER v9.12 Released

 

We released version 9.12 of DECIPHER on the 7th of December, 2016. Improvements include:

  • Loss Intolerance probability (pLI) scores from ExAC are now shown. You can choose to colour genes by their pLI scores in the genome browser. The pLI score is also shown on the gene tab and on the clinical overview tab.
    pli
  • The 2D protein view has been improved. DECIPHER sequence variants are now displayed above the protein domains, whilst the Pfam annotations are shown below the protein domains.

    pfam_dyrk1a

  • Sequence variants in the genome and protein browsers are now visually more distinct. Loss of function variants are shown in red and protein altering variants in yellow.
  • Users can now use Matchmaker exchangeto find patient matches in MyGene2 in addition to PhenomeCentraland GeneMatcher.
  • The pathogenicity evidence tab for sequence variants now allows users to record that pathogenicity evidence has been assessed and that none of the ACMG criteria are met. If pathogenicity evidence has been assessed for a variant, a link to the evidence is now shown in the genotype table below the pathogenicity contribution status.

DECIPHER v9.11 Released

 

We released version 9.11 of DECIPHER on the 2nd of November, 2016. Improvements include:

  • Patient sequence variant pathogenicity evidence can now be recorded based on the pathogenicity evidence given under ACMG standards and guidelines when adding or editing a sequence variant.
    pathogenicity evidence tab
  • Composite face images created from individuals with de novo mutations in twelve developmental genes can now be viewed with other quantitative data on the gene tab when looking at a sequence variant. These images highlight facial dysmorphologies specific to certain gene.

    composite-face

    Composite face of 19 patients with pathogenic sequence variants in KMT2A

  • The phenotyping interface has been remodelled to allow patient phenotype information to be added more easily.
    phenotyping interface
  • Classes of variants have been changed to a five-tier terminology system in line with ACMG recommendations; definitely pathogenic (>99%), likely pathogenic (>90%), uncertain significance (10-90%), likely benign (<10%) and benign (<1%). The possibly pathogenic class (>80%) has been removed.
  • Filters have been added to the transcript track allowing you to filter on non-coding/coding genes and filter on DD and Morbid genes.
  • Phenotypes have been added to overlapping syndromes page
  • Bulk upload template has changed: header row, allowed values for mother/father status, allowed values for pathogenicity.

DECIPHER v9.10 Released

 

We released version 9.10 of DECIPHER on the 10th of August, 2016. Improvements include:

  • Bulk Upload via HGVS: you can now deposit sequence variants in bulk using a complete HGVS code instead of chromosomal position. There is a new Bulk Upload CSV/Excel template for you to use in this case.

    HGVS Bulk Upload

    NB: If you have a complete HGVS code, you could already deposit sequence variants individually this way.

  • Prenatal patient records (patients initially referred to a clinicial geneticist before birth) can now also be deposited via Bulk Upload.
  • Project pages now load much faster, particularly in cases where projects have thousands of patient records.

DECIPHER Data Centre essential maintenance and website downtime

 

Due to essential Data Centre maintenance, the DECIPHER website will be unavailable from 17:00 BST on Friday 26th August 2016 BST until 11:00 BST on Tuesday 30th August 2016.
If you require further information please contact decipher@sanger.ac.uk.
We apologise for any inconvenience caused.

DECIPHER v9.9 Released

 

We released version 9.9 of DECIPHER on the 29th of June, 2016. Improvements include:

  • Developmental milestones and growth measurements of your patient are now shown on the gene tab when looking at a Sequence Variant: Four of the nine growth and developmental charts for EP300
  • Splice acceptor/donor variants are now shown on proteins
  • 3D protein structures now have a reset button so you can restore a protein-wide view if you have moved the protein out of view

We’ve also been working in the background to prepare as the clinical community transitions to GRCh38.

DECIPHER v9.8 Released

 

We released version 9.8 of DECIPHER on the 25th of May, 2016. In addition to the new features below, please note that starting on 23rd June, we will be activating our “two-year hold” policy: unshared patients can be stored in DECIPHER for up to two years while preliminary pathogenicity assessments are made and informed consent is obtained and recorded for sharing variants. Once patient data is shared (either in a consortium or by consenting patients and variants for open-access release), patients will continue to be available indefinitely. Emails have already been sent out to those with unshared patient data entered before May 2014, and logged-in depositors can check the status of any patient (including how long they have left to obtain informed consent, if relevant) by visiting the patient page.

  • Gene pages and views (under the clinical tab) now include plots of quantitative data associated with patient genes, including:
    • Height
    • Weight
    • Birth Weight
    • Occipital Frontal Circumference
    • Social Smile
    • Sat Unaided
    • Walked Unaided
    • First Words
    • Sex Ratio

    Pictured: four of the nine possible charts, showing Height, Weight, OFC and Social Smile for open-access DECIPHER patients with sequence variants marked pathogenic in EP300.

    This helps us to see that patients with EP300 variants appear to be more likely to be smaller and lighter, and have much smaller OFC than either a normal distribution or the typical DECIPHER patient. The data does not show any clear difference in the time when EP300 children exhibit a social smile.

    Growth and development charts are shown where sufficient data exists in DECIPHER (minimum five patients for any chart); physical measurements are shown as standard deviations from the median, adjusted for age and sex.

    This data is taken only from patients with open-access DECIPHER variants in the gene in question. Most of this data will have been gathered through the Deciphering Developmental Disorders project.

  • Consent button and status on patient pages: If you are a depositor, you will see a green ‘Consent’ button you can use to record informed consent for open-access sharing on patient records where consent has not yet been recorded.
    Click on the green consent button to make register consent for open-access sharing of patient genotype and phenotype data.
  • Ligands and other structures marked “hetero atoms” in the 3D protein structure view are now displayed using a “ball-and-stick” view, as displayed below.

    Hetero Atoms in DECIPHER's protein view

    MAP2K1 (PDB structure 3EQC) with ligand and DECIPHER variant. The location of variants, in particular, their proximity to binding sites etc. may be useful in making assessments of pathogenicity.

  • When viewing patient images, users may now opt for a black border surrounding the image (useful for retinal imaging).

DECIPHER v9.7 released

 

We released version 9.7 of DECIPHER on the 27th of April, 2016. Our headline feature in this release is a 3D protein view: a visualisation of a deposited sequence variant on an experimentally determined protein structure (where available) from the Protein Data Bank (PDB). Where there are experimental structures available for a region that contains one or more open-access sequence variants, these can be seen from our gene pages (e.g. MECP2 or TBL1XR1). Then, click on one of the green bars on the protein domain view (representing PDB structures and their coverage) and choose “view” to see the variants we have in the region covered by the structure in the 3D view.

3D view of a MECP2 structure with mapped DECIPHER variants.

3D view of a MECP2 structure with mapped DECIPHER variants.

TBL1XR1 3D view

3D view of a TBL1XR1 structure with mapped DECIPHER variants.

We have also made many other under-the-hood changes to DECIPHER to allow us to roll out new features in future releases!

DECIPHER v9.6 released

 

Continuing our incremental update cycle to DECIPHER functionality, we have released v9.6 on the 23rd of March, 2016. This update has many improvements to existing functionality including the following:

  • Protein domain views are now interactive and include new features
    • Overlapping variants: Overlapping and closely positioned DECIPHER open-access variants are now clearly separated and visible.
    • ExAC variants, PDB structures and protein secondary structures: We have mapped ExAC missense variants (as a histogram) and Loss-of-Function variants (as discrete bars) on the protein domain. In addition, available protein 3D structures from the Protein Data Bank (with links to the relevant structure) can also be seen. We have also added secondary structure information to the protein domain views for the regions for which a 3D structure is available.
    • Protein view zoom and pan: The protein domain view is now fully interactive and supports zoom and pan functions. Use the middle mouse scroll wheel to zoom in and out, or select a region with shift+ left-mouse button to choose a region to zoom into. Click on the image below to see an example.
      Screen Shot 2016-03-22 at 15.32.18
  • Improvements to Gene-Phenotype Table: In order to prioritise the display of more relevant phenotypes associated with a gene, we are now using the ICHPT terms to filter recorded phenotype terms.
  • Genes: The gene browser table has been improved by the addition of a count of the number of open-access variants in DECIPHER for each gene. In addition, more external links are available from this table to GeneCards, ArrayExpress and Protein Atlas. These links are also available from the individual gene pages themselves.
    Screen Shot 2016-03-21 at 13.29.14
  • Other notable changes:

DECIPHER v9.5 released

 

DECIPHER has been updated to version 9.5 today (17th February, 2016). This release brings new features and enhancements including:

  • Phenotype ontology update: We have updated the version of the Human Phenotype Ontology (HPO) to take advantage of the many new terms introduced since the last major update to HPO in DECIPHER (Summer 2013).
  • Replacement to obsolete HPO terms: Where a previously entered term has been made obsolete in the new version, we have moved the term to a suggested replacement. These are easily identified on the patient phenotype pages and may be replaced by a moreappropriate term (if necessary), or the suggestion accepted by the depositor.
  • Capture of clinical modifiers of HPO: In order the patient phenotypes may be recorded more accurately, we have enabled the capture of clinical modifiers that can record severity, onset, laterality, age of onset or diagnosis with every phenotype.
    Improvements to phenotype capture in DECIPHERImprovements to phenotype capture in DECIPHER.
  • Protein Domain Views: Sequence variants that affect coding regions can now be visualised on an interactive protein domain view of the expressed protein. Similarly, all openly-accessible variants deposited in DECIPHER for a gene can be visualised on this protein domain view. We hope this will help make the interpretation of the variant easier.
    Screen Shot 2016-02-16 at 20.10.27
  • Improvements to search
    • Genes in the pseudoautosomal regions (PAR) of chromosome Y are now available to search (like SHOX).
    • Finding genes in a chromosomal region is now easier! A new search result tab will have a list of genes overlapping the query. To see a list of genes in band 7p22.1 click here.

DECIPHER Video Tutorials

 

We are producing a series of video tutorials that showcase different aspects of the DECIPHER platform. Please subscribe to the DECIPHER YouTube channel to be kept updated on new tutorials as and when produced. We also welcome your suggestions for new tutorials.

DECIPHER v9.4 Released

 

Version 9.4 of DECIPHER was released on Wednesday 2nd December and includes the following new features:

  • Phenotype Browser: We are very happy to present a brand new feature for visually exploring DECIPHER phenotypes using the Human Phenotype Ontology (HPO). The phenotype browser is an interactive tool that ties in with our search system to list patients that contain that specific phenotype or its descendant terms. A short video tutorial demonstrating this new tool can be seen here.
  • Search: Sequence variants can now be found using Ensembl transcript identifiers in search. To find all patients in DECIPHER containing a variant in ENST00000346085, prefix your query with ‘transcript:’ for example: transcript:ENST00000346085.
  • Genome Browser
    • Automatic highlighting of selected variant makes it easier to identify a variant if there are multiple features on the same track.
    • Track resize controls have improved visibility.
    • Transcript and Sequence Conservation tracks now show amino acid 3-letter codes.Genome Browser
  • Miscellaneous
    • New “Browse” location on top of page to explore the genome, phenotypes and syndromes as well as genes and gene disorders.
    • Improvements to Bulk Upload template files to allow responsible contacts to be uploaded.
    • Phenotype browser now available for Gene and Project Overview pages
    • Update to GeneReviews Gene Disorders. Updates to reference data from various sources.
    • Internal Matchmaker sends out email to watcher when a new match is available.

DECIPHER v9.3 Released

 

Version 9.3 of DECIPHER was released on Wednesday 21st October and includes the following new features:

  • Gene Pages: Every gene now has its own automatically generated page containing information about the gene, collated phenotypes observed in DECIPHER consented sequence variants and other useful stuff! Please see: https://decipher.sanger.ac.uk/gene/SCN2A for the automatically generated page for SCN2A. We have also added links to the gene pages from the gene symbol on patient pages.
  • Screen Shot 2015-10-21 at 08.53.52

  • Extended Patient Information: The patient information section has been expanded for all DECIPHER patient records to allow entry of additional information including details of pregnancy and birth, developmental milestones and growth measurements. All new items are optional but could be useful in creating a complete record for the patient in DECIPHER.The additional information is only available to view for the depositing project regardless of patient consent status.
  • Screen Shot 2015-10-21 at 09.11.16

    Screen Shot 2015-10-21 at 09.11.29

  • Search: Searching by phenotypes is now possible using HPO identifiers. Please prefix your query with “hpo:” followed by the HPO ID e.g. hpo:100024 to find all patients accessible to you in DECIPHER with the phenotype “Conspicuously happy disposition”.
  • Genome Browser
    • There is only one SNV legend (and you can move it around)
    • ClinVar and HGMD variants are now coloured by consequence
    • ClinVar, HGMD, and dbSNP popups have been tweaked
  • Dosage Sensitivity Scores: DS scores on depositions of copy-number variants now take account of exon positions, and we have restored the graphs showing the deposited CNV dosage sensitivity score against background population data.

DECIPHER v9.2 Released

 

Version 9.2 of DECIPHER was released on Wednesday 16th September and includes the following new features and enhancements:

Deposition

  • HGVS code enabled deposition of sequence variants. Registered users can now quickly deposit their sequence variants by using standard coding- or genome-based HGVS strings. Upon successful interpretation, DECIPHER will automatically fill in chromosome, start, reference allele, alternate allele and transcript information.
  • Assistance in choosing transcripts for sequence variant deposition. If you’re unsure of the exact transcript while depositing sequence variants, DECIPHER will suggest transcripts based on the chromosomal location provided, thereby making variant deposition easier.

    DECIPHER HGVS-based variant deposition.

    DECIPHER HGVS-based variant deposition.

Visualisation

  • Re-order browser tracks from the tracks menu. Re-ordering tracks in DECIPHER Genoverse browser became even easier! You can re-order tracks from within the “Tracks” menu. To re-order tracks, click on “Tracks” and then simply move currently enabled tracks the way you want them arranged.
  • Updated Population Copy-Number variants. We have included an updated version of population CNV data in Genoverse. The context menu now includes actual counts and frequencies making it easier to interpret complex regions where both deletions and duplications are commonly seen.

    Updated population CNV track.

    Updated population CNV track.

  • Protein sequence on transcripts. At high zoom levels, transcripts will also show protein sequence.
  • Sequence track. A separate genomic sequence track is now available to view genomic sequence when viewing copy-number variants.
  • Filter to exclude one’s own patients. You can now choose to exclude your own overlapping patients from the DECIPHER: Copy-number variants or DECIPHER: Sequence variants track to make comparative analysis easier.

Analysis

  • Updated OMIM Morbid IDs. OMIM phenotypes have been updated leading to a higher and more accurate coverage across the genome.
  • Overlapping patients. Are now sorted by decreasing functional similarity scores. New filter to exclude one’s own overlapping patients from this table.

DECIPHER v9.1 Released

 

Version 9.1 of DECIPHER was released on Wednesday 19th August and introduces the following new features and enhancements:

  • All new patients are associated with a point of contact. By default this will be the person creating the patient record. However, patient consent can only be recorded if the responsible contact is a clinician; it is the clinician who must establish that informed consent has been given. For existing patients who do not have a contact point assigned yet, the project coordinator has now been assigned.
  • Genoverse:
    • Genoverse can now be made fullscreen on most browsers.
    • Selecting a region tells you the chromosome, start and end position of the region you’ve selected.
    • You can now highlight features and regions, making it easier to compare features in multiple tracks.
    • When viewing a sequence variant, the transcript the variant belongs to will always be at the top of the transcripts track and will be shaded.
    • Feature and tracks menu are now opaque and icons have been standardised.
    The Genoverse Browser in DECIPHER v9.1, showing some of the new features.
  • Making contact requests are now easier if your own patients are in DECIPHER. When making contact requests, you can now add automatically-generated summaries of your own overlapping patients to the message.

    Clicking 'add to message' will add a summary of your patient to your contact request

  • Patient copy-number variant to copy-number variant overlap can be filtered by the HGNC name of a common gene.
  • Intergenic sequence variants can now be deposited. A transcript is not required but the gene the variant interacts with is required.

DECIPHER v9.0 Released

 

Version 9.0 is a major update to DECIPHER and was released on the 8th of July, 2015. Apart from many improvements to the overall look-and-feel of the website, we have introduced the following salient features in this release.

    • New look main landing page: We have made changes to the front page to make it easier to find items including login, database statistics, help documents etc.
    • Internal Matchmaker: Save time and find new matching records in DECIPHER! Get notified when a new variant matching one in your patient is seen in DECIPHER. Activate by clicking the bell icon next to your publicly shared variants in your consented patients to follow the variant. A notification will be generated automatically when a new variant functionally similar to yours is made available in DECIPHER. Access your notifications by logging back into DECIPHER periodically.

Internal Matchmaker: Following a copy-number variant Internal Matchmaker: Following a sequence variant

    • External Matchmaker: DECIPHER is part of the Matchmaker Exchange project (MME). The MME provides a robust and systematic approach to rare disease gene discovery, through the creation of a federated network connecting databases of genotype and rare phenotypes.Using a common Application Programming Interface (API) connected databases (currently PhenomeCentral and GeneMatcher) will be queried for patient records that share similarity with your anonymous consented patients and the results will be displayed below. Find the “Matchmaker” tab on your patient page between “Karyotype” and “Citations”.

MME API: Finding matches in other connected databases

    • Introducing “My Dashboard”: Dashboard is a page that is specific to you and includes a collection of items pertinent to your use of DECIPHER. We have included mechanisms to create or access your patients, or manage variants you are following (for automatic notifications when other matching variants are deposited in DECIPHER). You need to be logged in to view the dashboard.
    • Genoverse
      • New Browser Tracks
        • Sequence Conservation Track: Showing protein sequence conservation across species for orthologous genes.
        • ExAC: Variants identified by the Exome Aggregation Consortium with genotype and allele counts.
      • Updated Features
        • Directionality of Genes.
        • CNV Filters for pathogenicity: Choose to see all, pathogenic, uncertain or benign CNVs using track filters.
        • CNV Filters for size: Choose to exclude overlapping DECIPHER CNVs based on size using track filters.
        • CNV Shading: CNVs are now shaded according to pathogenicity.
        • Population Data represented in dbSNP track (where available)
        • Improvements to track-specific help.
    • Functional Similarity Scores: Overlapping variants now have a functional similarity score associated with them. This is an estimate of the likelihood that the overall effects of two variants are similar and can be used to prioritise variants by relevance. This score is arrived at by comparing the type of effect the variants are believed to have (e.g. gain, loss, VEP consequence), and, for CNVs, how many genes the variants affect. You can find functional similarity scores under the “Overlapping Patients” section when viewing a patient variant.
    • Dosage-sensitivity scores and sampling probabilities: We now automatically calculate dosage sensitivity (DS) scores for all CNVs deposited to DECIPHER. DS scores provide an estimate of the likely pathogenicity of the variant based on log-odds scores of predicted haploinsufficient genes within a copy-number variant. Higher scores indicate that the CNV is likely to be pathogenic while low or negative scores could be indicative of non-pathogenicity.

  • Empowering Project Coordinators: Project Coordinators in DECIPHER will now need to login and approve any membership requests. They will also be able to keep track of the users with access to their projects and be able to revoke access for users who are no longer required to have access to the project.

DECIPHER v8.9 Released

 

Version 8.9 of DECIPHER was released on Wednesday 13th May and introduces the following new features and enhancements:

  • Search: Thank you for your valuable feedback on search. The search box will now always start a new search unlike in previous versions. Once a search has been executed, it may be modified from the “Refine Search” presented on top of the page above the search results.
  • Contacts: We have made access to the contacts tab easier than before by adding an explicit contact icon on all tables that show patient-specific data.
  • Notification Centre: We are rolling out a notification centre for our registered users. This is located on the top right of the page next to your login name. The notification centre will provide information pertinent to your account or patient data held in your name. In the initial release this notification centre provides warning about very large CNVs in your data (>25mb) and we encourage you to look at these results and update these records or delete as necessary.
  • Updates: Gene Reference, LSDB, HGMD and ClinVar data have been refreshed.
  • Improvements to the way DECIPHER records Consent. Informed consent from the patient may now be recorded without adding a variant.

DECIPHER v8.8 Released

 

Version 8.8 of DECIPHER was released on Wednesday 8th April and introduces the following new features and enhancements:

  • Absent Phenotypes: When adding phenotypes to a patient, you can now add explicitly ‘absent’ phenotypes which might be expected or relevant which the patient does not exhibit.

    Phenotype Absence is indicated by selecting the 'absent' valiue from a dropdown when the phenotype has been added to a patient

  • Genoverse Browser: (not available on out-dated internet browsers e.g. Internet Explorer 8)
    • If you are interested in exploring a region, you can browse DECIPHER usingGenoverse directly from the navigation bar at the top of the page.
    • The display of LSDB data has been improved in regions with several items.
  • Large CNVs: We no longer accept CNVs larger than 25Mb for usability and performance reasons. DECIPHER aims to match up patients’ microduplications, microdeletions and plausibly pathogenic sequence variants. Large CNVs which have already been deposited remain in DECIPHER, but new depositions cannot exceed 25Mb.
  • Updated Reference Data: including latest gene reference data

DECIPHER v8.7 released

 

Version 8.7 of DECIPHER introduces the following new features and enhancements.

  • Mitochondrial Genome: DECIPHER can now accept CNVs and/or SNVs from the mitochondrial genome. Two new values specific for mitochondrial inheritance – Mitochondrial homoplasmy and Mitochondrial heteroplasmy have been included in the deposition interface.

Mito1

  • DDD Research Variants now have their own specific variant pages that may be used to view information regarding this variant across Overview, Browser and Overlapping DECIPHER patient tabs. A “Contacts” option provides a mechanism to initiate contact for information and collaboration via DECIPHER.
  • DECIPHER Search
    • Searching on phenotypes now includes all children terms in the search. This means that a search for “microcephaly” will also include children terms from the Human Phenotype Ontology including “Congenital Microcephaly, Progressive Microcephaly, Postnatal Microcephaly”.
    • Search now also returns results from DDD Research Variants.
  • Photographs: A larger watermarked version of deposited photographs can now be accessed in DECIPHER for authorised users.
  • Pre-Natal Data: DECIPHER now supports the deposition of pre-natal data by capturing weeks of gestation between 20-42.
  • Updated Haploinsufficiency (HI) Scores: We have updated reference gene data with V3 of the HI predictions. The HI predictions now cover over 19000 genes.
  • Updated Reference Data: Including latest gene reference data and gene disorder data.

ClinGen/DECIPHER Meeting, May 27-28, 2015

 

clingen-DECIPHER-2015-websitebanner-processor-v13-constant-contact

Register now for ClinGen/DECIPHER 2015!

May 27-28, 2015

Renaissance Washington, DC Downtown

United by our common goals of leveraging data sharing and collaboration to improve our understanding of human genomic variation, ClinGen and DECIPHER are pleased to co-host this two day meeting (formerly the ICCG meeting). Topics will include:

  • Curating Gene-Disease Relationships
  • Initiatives Facilitating Clinical Genomic IT Development
  • Integrated Approaches to Informed Consent
  • Lessons Learned from Aggregating Population and Patient Data
  • Next Generation Bio-banking Strategies
  • Tools and Approaches to Support Sequence and Structural Variant Assessment
  • Introducing Genomics to the Practice of Medicine

Registration is now open.

To take advantage of early bird pricing, register before March 1, 2015!

Abstracts will be accepted until March 31, 2015.

Please visit the conference website for submission instructions.

Travel stipends are available for the most outstanding submissions. Questions? Please contact us at clingen@clinicalgenome.org.

DECIPHER v8.6 released

 

Version 8.6 of DECIPHER includes the following changes and enhancements.

  • Improved karyotype view on phenotype-based searches – The karyotype view is shown in a tab next to the tabular listing of results. The karyotype view switches to histogram view when there are many results. Click on any of the features to see an expanded view of the results at that position. (Will not work on older browsers like Internet Explorer 8).

Click on image to search DECIPHER on phenotype "seizures"

  • Initiate contact with depositing clinician from consented patient page – If you are not a logged in a user of DECIPHER, you can initiate contact with the depositing clinician using the “Contacts” button on the patient page. This contact request will be validated by the DECIPHER team and forwarded to the depositor.
  • Improved search: Search now includes searches by consequence (for example: missense_variant).
  • Karyotype view on project overview: As a logged in user, you can now see a karyotype view of all patients in your project. (Does not work on older internet browsers like Internet Explorer 8).

Project overview page karyotype view

  • Discriminate between own patients and other patients: We have enabled additional filters in the interactive genome browser and in the table of overlapping patients to enable exclusion/inclusion of own patients.

Patient Overlap Filters

Filter Patients in Genoverse

  • Miscellaneous changes to improve usability
    • Fewer clicks to get to your own patients from the “My Patients” link for logged in users
    • Additional filters in position-based search results to quickly identify CNV (gains/losses) and SNVs.

Project pinpoints 12 new genetic causes of developmental disorders

 

The Deciphering Developmental Disorders (DDD) project is working both nationwide and genome-wide with 12,000 UK families to diagnose their child’s developmental disorder, using a combination of exome sequencing and array technologies. The second flagship paper from the DDD study was published in Nature on Dec 24th (Article) reporting the identification of 12 new genes for developmental disorders. Pathogenic and likely pathogenic variants identified in DDD patients are shared via DECIPHER. Possibly pathogenic variants in novel genes are visible in DECIPHER in the ‘DDD research’ track.

DDD Paper Published!

 

Deciphering Developmental Disorders (DDD), which is funded by the Wellcome Trust Sanger Institute and the Health Innovation Challenge Fund, is working with 12,000 families to diagnose their child’s developmental disorder, demonstrating the feasibility and value of introducing large-scale sequencing diagnostics into health care. The first flagship paper from the DDD study is published in the Lancet today (Article) and (Commentary). Pathogenic and likely pathogenic variants identified in the DDD study are shared via DECIPHER.

DECIPHER v8.5 Released

 

This version includes the following changes and enhancements:

  • Search Enhancement: We are happy to introduce advanced search in DECIPHER with auto-suggest feature. The new search will allow you to combine multiple search terms into a single query for example
    • Location and phenotype 1 and phenotype 2 (e.g. 6:157099063-157531913, Cleft palate, Macrotia)
    • Gene and phenotype 1 and phenotype 2 and phenotype 3 (e.g. MVP, Short stature, Obesity, Intellectual disability)

    We urge you to familiarise yourself with the new search by following the short guide here.

  • Adding value to Patient Overlap information: Overlapping patients on patient variant pages allow the user to find other patients in DECIPHER that have overlapping variants.
    We now provide information about common genes in these overlaps which can be quickly used to find if the overlapping patient has a gene of interest also affected.common_genes
  • Matchmaker API 1.0: DECIPHER is now compliant with v1.0 of the Matchmaker Exchange application programming interface (API).
    The ‘Matchmaker Exchange’ project was launched in October 2013 to facilitate the matching of cases with similar phenotypic and genotypic profiles (matchmaking)through standardized APIs and procedural conventions across multiple databases.
    For more information, please see: Matchmaker Exchange Home.

DECIPHER v8.4 Released

 

This version includes the following changes and enhancements:

(Neither of these features will work on out-dated internet browsers e.g Internet Explorer 8)

  • Graphical Views – Provides at-a-glance view of patient distribution based on inheritance, pathogenicity etc. for overlapping patients.
  • DDD Research Variants: Variants of unknown significance in 816 undiagnosed children with developmental disorders in the UK DDD study (www.ddduk.org). Variants include validated functional de novo variants and rare loss-of-function homozygous, compound heterozygous and hemizygous variants in genes lacking both an OMIM-morbid status and common loss-of-function variants. Available as additional on-demand tracks on Genoverse browser.

DECIPHER v8.3 Released

 

This version includes the following changes and enhancements:

(Genoverse browser will not work on out-dated internet browsers e.g Internet Explorer 8/9)

  • Genoverse Browser: New “focus here” menu item on tracks to quickly focus (zoom-in or out) on region of interest. (User guide)
  • Gene Disorders and associated annotated variants from GeneReviews and ClinVar. Trusted variants track on genoverse browser. (Quick Look)
  • User e-mail addresses now hidden from DECIPHER contacts pages. All user-to-user contact requests are now via an online form to safeguard our user e-mail addresses
  • Updated Reference Data: non-coding genes included in reference data and Genoverse browser tracks. Easy toggle to switch this information on or off.
  • Graphical Breakdown of consequences predicted by the Ensembl Variant Effect Predictor (this will not work on out-dated internet browsers e.g Internet Explorer 8/9)
  • Miscellaneous improvements to web interface and optimisation of code

DECIPHER v8.2 Released

 

This version includes the following changes and enhancements:

(Genoverse browser will not work on out-dated internet browsers e.g Internet Explorer 8)

  • Genoverse Browser: Our interactive browser now remembers your settings (track order, track visibility, track properties) so you don’t have to!
  • Account Management: You can now change your password for accessing DECIPHER in-place (with email confirmation)
  • Variant Sharing: You can choose to share each variant in a patient independently (Public, One or more consortia or Private). Better representation of shared status
  • Updated Reference Data: Latest Release of DDG2P (20140718), HGNC Gene Symbols, Variants from LSDB, ClinVar, HGMD
  • Display of multiple values of OMIM/Morbid associated with genes
  • Improvements to phenotype entry
  • Other bug fixes and miscellaneous improvements to user interface

DECIPHER v8.1 Released

 

Version 8.1 brings further improvements to DECIPHER based on valuable feedback and useful suggestions from our users. This version includes the following changes and enhancements:

  • Variant level sharing. Users may choose which variants to make publicly available when consenting their patient data for anonymous sharing. At least one variant must be shared for a patient record to be shared anonymously. Variants that are not shared publicly are not visible in search results or the Genoverse browser for all users who are not part of the same project or consortium.
  • Print Report for patients includes graphical elements and listing of affected genes and overlapped patients. Users must choose the variant for which they wish to print a report if the entry contains more than one variant.
  • Better compatibility support for old internet browsers such as Internet Explorer 8 and 9
  • Other bug fixes and miscellaneous improvements to user interface

DECIPHER v8.0 Released

 

Release 8.0 of DECIPHER is a complete re-write of the system and uses modern web and database technologies to provide a robust platform for rapid implementation of future enhancements. In developing the new version, we have taken great care to ensure that no existing functionality has been lost and wherever possible, enhancements have been introduced to make deposition, visualisation and data retrieval easier.

  • A modern, cleaner user interface
  • Enhanced Genoverse browser features (this will not work on out-dated internet browsers e.g Internet Explorer 8)
  • Improvements to deposition interface and phenotyping tools
  • Improvements to bulk upload of Sequence and Copy-Number Variants (including in-place editing)
  • Enhanced gene filtering based on OMIM, OMIM Morbid or DDG2P
  • Distinguishing between own projects and projects that are part of a larger shared consortia of projects (eg DDD, NHS etc).

DECIPHER celebrates its 10th birthday!

 

29th February, 2004: DECIPHER name formalised

5th March, 2004: decipher.sanger.ac.uk website on development site

16th March, 2004: First DECIPHER workshop at the Wellcome Trust Sanger Institute

DECIPHER with Sequence Variation Released

 

DECIPHER now accepting sequence variation data

A significant upgrade to DECIPHER functionality has been rolled out. This upgrade brings many improvements and enhancements to DECIPHER including the deposition and analysis of sequence variants. Read more here.

Share your Research Data in DECIPHER

If you have high-quality research data (sequence or copy-number variation), why not maximise its reach by sharing within and via DECIPHER? Please write to decipher@sanger.ac.uk for more information.

Genome Browser

Follow this short handy guide to the new genome browser in DECIPHER to make best use of its capabilities (available here).

DECIPHER on OrphaNews

 

Dr. Helen Firth talks to OrphaNews about DECIPHER – a valuable database for researchers and clinicians (Link)