Dear All,
This is a reminder that the DECIPHER website and database will be moving from the Wellcome Sanger Institute to the European Bioinformatics Institute (EMBL-EBI) on 4-5 July and the website will be unavailable during this time. We have taken the decision for an extended downtime to ensure a smooth migration. The transition will not involve any changes to the address (URL), the appearance, or the functionality of DECIPHER. DECIPHER will join many other resources hosted by EMBL-EBI which are critical to DECIPHER's work, such as Ensembl and its Variant Effect Predictor (VEP), Gene2Phenotype and UniProt.
We apologise for any inconvenience caused by the downtime.
If you have any questions about the transition, please email contact(a)deciphergenomics.org<mailto:contact@deciphergenomics.org>
Best Regards
Julia, on behalf of the DECIPHER team
Julia Foreman PhD
DECIPHER Project Leader
Email: contact(a)deciphergenomics.org<mailto:contact@deciphergenomics.org>
Web: https://www.deciphergenomics.org
Twitter: @decipher_wtsi
Dear All,
The DECIPHER website and database will be moving from the Wellcome Sanger Institute to the European Bioinformatics Institute (EMBL-EBI) on 4-5 July and the website will be unavailable during this time. We have taken the decision for an extended downtime to ensure a smooth migration. The transition will not involve any changes to the address (URL), the appearance, or the functionality of DECIPHER. DECIPHER will join many other resources hosted by EMBL-EBI which are critical to DECIPHER's work, such as Ensembl and its Variant Effect Predictor (VEP), Gene2Phenotype and UniProt.
We apologise for any inconvenience caused by the downtime.
If you have any questions about the transition, please email contact(a)deciphergenomics.org
Best Regards
Julia, on behalf of the DECIPHER team
Julia Foreman PhD
DECIPHER Project Leader
Email: contact(a)deciphergenomics.org
Web: https://www.deciphergenomics.org
Twitter: @decipher_wtsi
Dear All,
Greetings from a sunny East Anglia.
In this update:
- DECIPHER v11.16 Released
o ClinGen Clinical Actionability information on gene pages
o Protein browser
§ Cardiac VariantFX case cohort data
§ "Settings" menu renamed to "Tracks and filters"
§ DECIPHER and ClinVar variant consequence filters
§ DECIPHER variant patient filter
o Gene-disease associations
§ Display of Gene2Phenotype information on gene pages
§ GenCC badges in gene tables
o Additional title tags
- Move to EBI
DECIPHER v11.16 Released
=============
You can also view this on the web at: https://www.deciphergenomics.org/about/news
ClinGen Clinical Actionability Report information is now displayed on gene clinical tabs for genes that, when significantly altered, confer a high risk of serious disease that could be prevented/ mitigated if the risk were known. Information for adult and paediatric subjects are available. In the following example a ClinGen Clinical Actionability report is available for Von Hippel Lindau Disease associated with variants in VHL: https://www.deciphergenomics.org/gene/VHL/overview/clinical-info
Cardiac VariantFX case cohort data is now displayed on the protein browser. This allows the visualisation of the distribution of case cohort data and allows users to browse the data. For each variant the allele number, count and frequency is displayed, with a link to a page which provides more in-depth cardiac case cohort information about the variant. The following example shows this feature for DSP: https://www.deciphergenomics.org/gene/DSP/overview/protein-genomic-info. In addition, the protein browser "Settings" menu has been renamed to "Tracks and filters" to increase findability. Consequence filters are now available for DECIPHER and ClinVar variants, allowing variants with only a defined predicted molecular consequence to be displayed. A DECIPHER variant patient filter is also available which allows only DECIPHER variants in, for example, "patients in my projects" or "patients not in my projects" to be displayed. These features can be viewed for ACTB here: https://www.deciphergenomics.org/gene/ACTB/overview/protein-genomic-info
The display of Gene2Phenotype gene/disease associations on gene pages has been updated, so that diseases associated with more than one panel are grouped, simplifying the display. This simplified view can be seen here for PTEN: https://www.deciphergenomics.org/gene/PTEN/overview/clinical-info. In addition, the strengths of gene/disease associations asserted by Gene2Phenotype and ClinGen in genes tables now match the colours used for those classifications by GenCC.
Finally, additional title tags are now available to allow users with multiple open tabs, to identify the relevant tab.
Move to EBI
=============
In early 2023, DECIPHER's hosting and development will transition from the Wellcome Sanger Institute (where DECIPHER began and has been based for the last 18 years) to the European Bioinformatics Institute (EMBL-EBI), which runs Ensembl and its Variant Effect Predictor (VEP), Gene2Phenotype, UniProt and many other resources which are critical to DECIPHER's work. Both institutes are committed to a smooth transition and the migration will not involve any changes to the address (URL), the appearance, or the functionality of DECIPHER.
The Deciphering Developmental Disorders (DDD) project (https://www.ddduk.org), which has recruited nearly 14,000 families in the UK and Ireland, will still deliver results through DECIPHER, while the research work will remain at Sanger.
=============
We look forward to your feedback and suggestions for improvement. Please use the "Feedback" button which is available on every page and fill in the simple form to get in touch with us. Your details will be filled in automatically if you are logged in.
Best Regards
Julia, on behalf of the DECIPHER team
Julia Foreman PhD
DECIPHER Project Manager
Email: contact(a)deciphergenomics.org<mailto:contact@deciphergenomics.org>
Web: https://www.deciphergenomics.org
Twitter: @decipher_wtsi
Dear All,
Greetings from a chilly East Anglia.
In this update:
- DECIPHER v11.15 Released
- Move to EBI
DECIPHER v11.15 Released
=============
You can also view this on the web at: https://www.deciphergenomics.org/about/news
Additional information modals about resources that DECIPHER display are now available across the website, which describe the resource and where to find additional information. These can be accessed by clicking on "?" icons. These modals also include the date at which DECIPHER last retrieved data from the resource, allowing users to know how current the data is. Information modals for ClinVar assertions and ClinGen expert panel interpretations can be viewed here (variant page for a variant in TCF4): https://www.deciphergenomics.org/sequence-variant/18-55228323-TTC-T/annotat…. Where relevant, modals describe how data is mapped between resources, as can be viewed here for HGNC data: https://www.deciphergenomics.org/sequence-variant/18-55228323-TTC-T/genes/T…
Move to EBI
=============
In early 2023, DECIPHER's hosting and development will transition from the Wellcome Sanger Institute (where DECIPHER began and has been based for the last 18 years) to the European Bioinformatics Institute (EMBL-EBI), which runs Ensembl and its Variant Effect Predictor (VEP), Gene2Phenotype, UniProt and many other resources which are critical to DECIPHER's work. Both institutes are committed to a smooth transition and the migration will not involve any changes to the address (URL), the appearance, or the functionality of DECIPHER.
The Deciphering Developmental Disorders (DDD) project (https://www.ddduk.org), which has recruited nearly 14,000 families in the UK and Ireland, will still deliver results through DECIPHER, while the research work will remain at Sanger.
=============
We look forward to your feedback and suggestions for improvement. Please use the "Feedback" button which is available on every page and fill in the simple form to get in touch with us. Your details will be filled in automatically if you are logged in.
Best Regards
Julia, on behalf of the DECIPHER team
Julia Foreman PhD
DECIPHER Project Manager
Email: contact(a)deciphergenomics.org
Web: https://www.deciphergenomics.org
Twitter: @decipher_wtsi
Julia Foreman PhD
DECIPHER Project Manager
Wellcome Sanger Institute / EMBL's European Bioinformatics Institute
Hinxton
Cambridge
E-mail: jf11(a)sanger.ac.uk<mailto:jf11@sanger.ac.uk>
https://www.deciphergenomics.org<https://www.deciphergenomics.org/>
Please note, I work on Tuesday and Friday mornings, all day Monday, Wednesday and Thursday
Dear All,
Greetings from a dry and humid East Anglia.
In this update:
- DECIPHER v11.14 Released
o pHaplo and pTriplo scores
§ Display of new scores
§ Removal of %HI scores
§ Updated dose sensitivity scores and sampling probabilities
o ACMG secondary findings v3.1
o Order of gene/disease association resources on gene pages
- Update to DECIPHER's consent and assent forms - transition to EBI
- Inactive DECIPHER Accounts
DECIPHER v11.14 Released
=============
You can also view this on the web at: https://www.deciphergenomics.org/about/news
pHaplo (deletion intolerance) and pTriplo (duplication intolerance) scores from the recent Collins et al., Cell paper (https://europepmc.org/article/MED/35917817) are now displayed in DECIPHER. These predictive scores are from an analysis of large rare copy-number variants and will assist in the identification of haploinsufficient and triplosensitive genes, supporting accurate variant interpretation. These scores are displayed on the clinical tab on gene pages and gene tables (example here: https://www.deciphergenomics.org/patient/401741/genotype/181219/genes). Genes can also be coloured according to pHaplo or pTriplo scores in the genome browser genes track. pHaplo will be the default colouring for the genes track except for when viewing duplications and other copy-number gains, in which case pTriplo will be used. Please note, genome browser configurations for the genes track for logged-in users have been reset to allow these default settings to be displayed.
CNV dosage sensitivity (DS) scores have been updated and are now calculated based on the pHaplo scores of individual genes within a deletion, or pTriplo scores of individual genes within a duplication (or other copy-number gain). Sampling probabilities (an estimate of the proportion of the general population that carry a rare deletion/duplication with a DS score as severe, or more severe than for the CNV being assessed) have also been updated. DS scores were previously calculated using pHI scores (Huang et al., 2010; https://europepmc.org/article/MED/20976243). The method for calculating the scores remains the same, except that we now only take into consideration MANE transcripts (or where there is no MANE, the best available transcript). These updated DS scores and sampling probabilities have improved predictive power in identifying deleterious CNVs. Please note, the new scores are not comparable with the old scores. All scores displayed on the DECIPHER website have been recalculated. The following example shows the updated scores for a deletion on chromosome 7: https://www.deciphergenomics.org/patient/271096/genotype/45676/browser
ACMG secondary findings reporting information has been updated to v3.1 (https://europepmc.org/article/MED/35802134). This version includes the addition of five genes, including four associated with cardiomyopathy (BAG3, DES, RBM20, TNNC1). This information is displayed on the clinical tab on gene pages, patient variant gene tabs and genes tables. Updated information can be viewed for RBM20 here: https://www.deciphergenomics.org/gene/RBM20/overview/clinical-info
The order of gene/disease association resources has been updated on the clinical tab on gene pages. Gene2Phenotype (https://www.ebi.ac.uk/gene2phenotype) gene/disease associations are now displayed at the top of the page. This change can be viewed for MYBPC3 here: https://www.deciphergenomics.org/gene/MYBPC3/overview/clinical-info
Update to DECIPHER's consent and assent forms - transition to EBI
=============
DECIPHER has been awarded a Wellcome grant to continue its work through to 2025. The grant provides for a transition of DECIPHER's hosting and development from the Wellcome Sanger Institute to the European Bioinformatics Institute (EMBL-EBI; https://www.ebi.ac.uk), which runs Ensembl and its Variant Effect Predictor (VEP), Gene2Phenotype and many other resources which are critical to DECIPHER's work.
The DECIPHER consent and assent forms, which provide consent for sharing patient data openly on the DECIPHER website, have been updated to reflect this transition and EMBL-EBI is now listed at the bottom of the forms. The assent form has also been reviewed to ensure consistency with the consent form. The updated consent (v8, 2022) and assent forms (v7, 2022) can be downloaded from the following page: https://www.deciphergenomics.org/about/downloads/documents. Please use the update versions going forward.
In relation to the transition to EMBL-EBI, Co-PI Helen Firth will remain the clinical lead; Matt Hurles will step back as co-PI but will remain involved as a collaborator and Fiona Cunningham, who leads EBI's Genome Interpretation Team, will join as co-PI. Both institutes are committed to a smooth transition and the migration will not involve any changes to the address (URL), the appearance, or the functionality of DECIPHER.
The Deciphering Developmental Disorders (DDD) project (https://www.ddduk.org), which has recruited nearly 14,000 families in the UK and Ireland, will still deliver results through DECIPHER, while the research work will remain at Sanger.
Inactive DECIPHER Accounts
=============
It is important that DECIPHER accounts are linked only to individuals who are currently actively working in research or clinical genetics and affiliated with their projects' lists. We will soon be locking a number of DECIPHER accounts which no longer appear to be in use to minimise the risk of unauthorised access. If you last logged into DECIPHER prior to 1 September 2020, please make sure you log in again using your email address and password, if you want to retain your access to DECIPHER.
We're very grateful for the coordinators who monitor their project's lists on an ongoing basis.
=============
We look forward to your feedback and suggestions for improvement. Please use the "Feedback" button which is available on every page and fill in the simple form to get in touch with us. Your details will be filled in automatically if you are logged in.
Best Regards
Julia, on behalf of the DECIPHER team
Julia Foreman PhD
DECIPHER Project Manager
Email: contact(a)deciphergenomics.org<mailto:contact@deciphergenomics.org>
Web: https://www.deciphergenomics.org
Twitter: @decipher_wtsi
Dear All,
Greetings from a sunny and warm East Anglia.
In this update:
- DECIPHER v11.12 Released
o New Cardiac Features
§ Variant Disease Cohort Allele Frequencies
§ Gene2Phenotype Gene/Disease Assertions
o Update to de novo Inheritance Terms
- Inactive DECIPHER Accounts
- Wellcome Funding and Move to EBI
DECIPHER v11.12 Released
=============
You can also view this on the web at: https://www.deciphergenomics.org/about/news
DECIPHER now displays cardiac variant allele frequencies. This data indicates if a variant has been observed in hypertrophic cardiomyopathy, dilated cardiomyopathy, or in healthy volunteers. This data will assist in variant interpretation and make it easier to know when to apply the ACMG/AMP sequence variant PS4 criterion during a variant pathogenicity assessment. Cohort ethnicity and age distributions are provided where available. The allele frequencies can be viewed on the "Annotation" tab on patient records, variant pages or protein variant pages under "Disease cohort" for the cardiac genes, where this is available. The following page displays hypertrophic cardiomyopathy cohort data for a variant in MYBPC3: https://www.deciphergenomics.org/protein-variant/ENSG00000134571-502-R-W/an…
Cardiac Gene2Phenotype gene/disease assertions are now displayed on gene pages and in gene tables, assisting with interpretation of variants in genes associated with cardiac disease. As with other Gene2Phenotype assertions, further information such as the mutation consequence can be viewed by clicking on the gene/disease assertion. Cardiac Gene2Phenotype gene/disease assertions for MYH7 can be viewed here: https://www.deciphergenomics.org/gene/MYH7/overview/clinical-info
These cardiac features complement the cardiac control cohort information, which provide quantitative estimates that a rare variant in a gene is causative of a disease, and cardiac mutational hot spots data that were released in April.
The "de novo" inheritance option has now been replaced with "de novo (parentage confirmed)" and "de novo (unconfirmed parentage)". This allows depositors to record confirmed parental relationships versus assumed parental relationships status for de novo variants, which is important when determining the strength given to case level data during a variant pathogenicity assessment, specifically for ACMG/AMP sequence variant criteria PS2 and PM6. Variants deposited prior to this release will be marked as unconfirmed, except for where depositing centres have let us know that the variants they have deposited are confirmed. If the de novo variants from your centre should be displayed as "de novo (parentage confirmed)", rather than "de novo (unconfirmed parentage)", please email contact(a)deciphergenomics.org<mailto:contact@deciphergenomics.org> and provide details. Please note that this change affects users depositing via bulk upload.
Inactive DECIPHER Accounts
=============
It is important that DECIPHER accounts are linked only to individuals who are currently actively working in research or clinical genetics.
We will soon be identifying and locking a number of DECIPHER accounts which no longer appear to be in use to minimise the risk of unauthorised access. If you last logged into DECIPHER prior to 17th June 2020, please make sure you log in again using your email address and password, if you want to retain your access to DECIPHER. After 17th June 2022, we intend to lock accounts which have not been accessed in the previous two years. If your account is locked, you will need to reset your password before you can regain access.
We're very grateful for the coordinators who monitor their project's lists on an ongoing basis.
Wellcome Funding and Move to EBI
=============
DECIPHER has been awarded a new Wellcome grant to continue its work through to 2025. Key goals include better support for variants in the non-coding genome, helping users find relevant functional evidence, and building models to link genes and disorders with phenotypes. The grant will allow us to keep DECIPHER up to date with best practice and emerging opportunities in clinical interpretation as the landscape evolves.
The grant also provides for a transition of DECIPHER's hosting and development from the Wellcome Sanger Institute (where DECIPHER began and has been based for the last 18 years) to the European Bioinformatics Institute (EMBL-EBI; https://www.ebi.ac.uk), which runs Ensembl and its Variant Effect Predictor (VEP), Gene2Phenotype and many other resources which are critical to DECIPHER's work. Co-PI Helen Firth will remain the clinical lead; Matt Hurles will step back as co-PI but will remain involved as a collaborator and Fiona Cunningham, who leads EBI's Genome Interpretation Team, will join as co-PI. Both institutes are committed to a smooth transition and the migration will not involve any changes to the address (URL), the appearance, or the functionality of DECIPHER.
The Deciphering Developmental Disorders (DDD) project (https://www.ddduk.org), which has recruited nearly 14,000 families in the UK and Ireland, will still deliver results through DECIPHER, while the research work will remain at Sanger.
=============
We look forward to your feedback and suggestions for improvement. Please use the "Feedback" button which is available on every page and fill in the simple form to get in touch with us. Your details will be filled in automatically if you are logged in.
Best Regards
Julia, on behalf of the DECIPHER team
Julia Foreman PhD
DECIPHER Project Manager
Email: contact(a)deciphergenomics.org<mailto:contact@deciphergenomics.org>
Web: https://www.deciphergenomics.org
Twitter: @decipher_wtsi
Dear All,
Greetings from a sunny East Anglia.
In this update:
- DECIPHER v11.11 Released
o New cardiac features
§ Case/control cohort data
§ Hot spot regions (PM1)
o ACMG secondary finding genes
o Recommendations for reporting of cancer susceptibility genes
o Links to Transcript Archive
o GenCC classification colouring for ClinGen and G2P gene/disease associations
- Planned Update to Inheritance Terms
- Inactive DECIPHER Accounts
- Wellcome Funding and Move to EBI
DECIPHER v11.11 Released
=============
You can also view this on the web at: https://www.deciphergenomics.org/about/news
DECIPHER now displays case/control cohort information for cardiac disease genes to demonstrate the confidence of the gene-phenotype relationships where these cohorts are available. Case/control cohort data can be viewed for MYH7 in relation to dilated cardiomyopathy and hypertrophic cardiomyopathy here: https://www.deciphergenomics.org/gene/MYH7/overview/clinical-info
For genes associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and Long-QT syndrome, we now show regions considered to be mutational hot spots or critical domains on the protein browser. This will make it easier to know when to apply the ACMG PM1 criterion during a variant pathogenicity assessment. The regions are annotated for the disease and the strength of evidence recommended. The following link shown the PM1 domain for MHY7 associated with hypertrophic cardiomyopathy: https://www.deciphergenomics.org/gene/MYH7/overview/protein-genomic-info
Where the ACMG recommend reporting secondary findings, we have added this information to the clinical tab on gene pages, patient variant gene tabs and genes tables. Secondary finding information for RB1 can be viewed here under the Management resources section here: https://www.deciphergenomics.org/gene/RB1/overview/clinical-info
Recommendations for reporting of cancer susceptibility genes as published in Talukdar et al., 2019 (https://europepmc.org/article/MED/31018999) are now included in the description of DECIPHER CNV syndromes on the Overview tab, where those syndromes involve a cancer susceptibility gene. This information can be seen for Familial Adenomatous Polyposis here: https://www.deciphergenomics.org/syndrome/49/overview
Links to Transcript Archive (TARK, https://tark.ensembl.org) are now provided if a user attempts to deposit a variant using an old transcript version. TARK provides interfaces to allow users to visualise the differences between transcript versions. The following TARK page allows the comparison of NM_001101 ACTB transcripts: https://tark.ensembl.org/web/transcript_details/NM_001101.4/
In addition, the strengths of gene-disease relationships asserted by ClinGen and G2P on gene tabs now match the colours used for those classifications by GenCC, (whose data sources include ClinGen and G2P). This can be viewed for FGFR1 here: https://www.deciphergenomics.org/gene/FGFR1/overview/clinical-info
Planned Updated to Inheritance Terms
=============
In May we plan to remove the "de_novo" inheritance option and start supporting the inheritance options "de novo (parentage confirmed)" and "de novo (unconfirmed parentage)". This will allow depositors to record confirmed parental relationships versus assumed parental relationships status for de novo variants, which is important when determining the strength given to case level data during a variant pathogenicity assessment.
We plan to update all deposited "de novo" variants to "de novo (unconfirmed parentage)", unless we know that parentage has been confirmed (e.g. when the project contains trio exome data, in these cases will be updated to "de novo (parentage confirmed)").
If the de novo variants from your centre should be updated to "de novo (parentage confirmed)", rather than "de novo (unconfirmed parentage)", please email contact(a)deciphergenomics.org<mailto:contact@deciphergenomics.org> and provide details.
Inactive DECIPHER Accounts
=============
It is important that DECIPHER accounts are linked only to individuals who are currently actively working in research or clinical genetics.
We will soon be identifying and locking a number of DECIPHER accounts which no longer appear to be in use to minimise the risk of unauthorised access. If you last logged into DECIPHER prior to 17th June 2020, please make sure you log in again using your email address and password, if you want to retain your access to DECIPHER. After 17th June 2022, we intend to lock accounts which have not been accessed in the previous two years. If your account is locked, you will need to reset your password before you can regain access.
We're very grateful for the coordinators who monitor their project's lists on an ongoing basis.
Wellcome Funding and Move to EBI
=============
DECIPHER has been awarded a new Wellcome grant to continue its work through to 2025. Key goals include better support for variants in the non-coding genome, helping users find relevant functional evidence, and building models to link genes and disorders with phenotypes. The grant will allow us to keep DECIPHER up to date with best practice and emerging opportunities in clinical interpretation as the landscape evolves.
The grant also provides for a transition of DECIPHER's hosting and development from the Wellcome Sanger Institute (where DECIPHER began and has been based for the last 18 years) to the European Bioinformatics Institute (EMBL-EBI; https://www.ebi.ac.uk), which runs Ensembl and its Variant Effect Predictor (VEP), Gene2Phenotype and many other resources which are critical to DECIPHER's work. Co-PI Helen Firth will remain the clinical lead; Matt Hurles will step back as co-PI but will remain involved as a collaborator and Fiona Cunningham, who leads EBI's Genome Interpretation Team, will join as co-PI. Both institutes are committed to a smooth transition and the migration will not involve any changes to the address (URL), the appearance, or the functionality of DECIPHER.
The Deciphering Developmental Disorders (DDD) project (https://www.ddduk.org), which has recruited nearly 14,000 families in the UK and Ireland, will still deliver results through DECIPHER, while the research work will remain at Sanger.
=============
We look forward to your feedback and suggestions for improvement. Please use the "Feedback" button which is available on every page and fill in the simple form to get in touch with us. Your details will be filled in automatically if you are logged in.
Best Regards
Julia, on behalf of the DECIPHER team
Julia Foreman PhD
DECIPHER Project Manager
Email: contact(a)deciphergenomics.org<mailto:contact@deciphergenomics.org>
Web: https://www.deciphergenomics.org
Twitter: @decipher_wtsi
Julia Foreman PhD
DECIPHER Project Manager
Wellcome Sanger Institute
Hinxton
Cambridge CB10 1SA
Tel: 01223-492392
E-mail: jf11(a)sanger.ac.uk<mailto:jf11@sanger.ac.uk>
https://www.deciphergenomics.org
Please note, I work on Monday and Tuesday mornings, all day Wednesday, Thursday and Friday
[decipher image_small]
Dear All,
Greetings from a grey and murky East Anglia.
In this update:
- DECIPHER v11.9 Released
o Regulatory features genome browser track
o AlphaFold predicted 3D protein structures
o neXtProt functional annotations
o MANE Plus Clinical transcripts
o Links to IEMbase
o ClinGen Expert Panel Interpretations
o ClinGen SVI recommendations for population data
o Protein browser
§ Conservation track
§ Number of transcripts sharing each exon
o Grantham distance scores
DECIPHER v11.9 Released
=============
You can also view this on the web at: https://www.deciphergenomics.org/about/news
A regulatory features track in now displayed in the genome browser which displays features from the Ensembl Regulatory Build, which are predicted to regulate gene expression. This will particularly assist the interpretation of variants in the non-coding genome.
AlphaFold predicted 3D protein structures can now be accessed through the protein browser. AlphaFold was first published in July and DECIPHER users can now view a patient's variant on the predicted structure to improve interpretation in the clinic. The AlphaFold predicted structure for EP300 can be viewed here: https://www.deciphergenomics.org/gene/EP300/overview/protein-genomic-info
Manual annotations that capture the phenotypic effect of genetic variations from the neXtProt knowledgebase are now displayed on a functional annotation tab. This includes functional annotation for variants in 130 clinically important genes, including ion channels, protein kinases and cancer genes. Functional annotation for MSH2 p.Gly322Asp can be viewed here: https://www.deciphergenomics.org/protein-variant/ENSG00000095002-322-G-D/an…
MANE Plus Clinical transcript annotations are now displayed in DECIPHER. These transcripts are additional transcripts per locus (to the MANE Select transcript) necessary to support clinical variant reporting, e.g. which contain known pathogenic variants. MANE Plus Clinical transcripts are displayed in the genome browser and in the variant deposition form.
Links to IEMbase, an online expert-curated inborn errors of metabolism (IEM) knowledge base are now provided on gene pages. Links for GRIN1 can be seen for here under the Management resources section: https://www.deciphergenomics.org/gene/GRIN1/overview/clinical-info
ClinGen Expert Panel Interpretations are now displayed on ClinVar/ClinGen annotation tabs (https://www.deciphergenomics.org/sequence-variant/18-55228323-TTC-T/annotat…). In addition, ClinGen SVI recommendations regarding the use of population data when interpreting sequence variants, are also now displayed in the pathogenicity evidence interface. ClinGen SVI recommend BS1 and BA1 can be met by population databases, whilst BS2 can only be met when you have a well phenotyped individual known to be without the disease.
A conservation track displaying the protein sequence of orthologous genes is now available on the protein browser. In addition, the number of transcripts sharing each exon in displayed, which can be important when interpreting single-exon deletions. These new features can be viewed for EP300 here: https://www.deciphergenomics.org/gene/EP300/overview/protein-genomic-info
Grantham distance scores, which predict the effect of substitutions between amino acids based on chemical properties, are displayed on the VEP consequence tab. Grantham distance scores for a Tyrosine to Phenylalanine substitution can displayed here: https://www.deciphergenomics.org/patient/293944/genotype/200339/annotation/…
=============
We look forward to your feedback and suggestions for improvement. Please use the "Feedback" button which is available on every page and fill in the simple form to get in touch with us. Your details will be filled in automatically if you are logged in.
Festive Wishes
Julia, on behalf of the DECIPHER team
Julia Foreman PhD
DECIPHER Project Manager
Email: contact(a)deciphergenomics.org<mailto:contact@deciphergenomics.org>
Web: https://www.deciphergenomics.org
Twitter: @decipher_wtsi
Dear All,
Greetings from sunny, chilly, autumnal East Anglia.
In this update:
* Wellcome funding and move to EBI
* DECIPHER v11.8 Released
o New sequence variant and protein pages
o Clinvar annotation tab
o Deposition of mosaicism by tissue, for mosaic UPD variants
* Optional DECIPHER ClinVar submission
Wellcome funding and move to EBI
=============
We are pleased to announce that DECIPHER has been awarded a new Wellcome grant to continue its work through to 2025.
Key goals include better support for variants in the non-coding genome, helping users find relevant functional evidence, and building models to link genes and disorders with phenotypes. The grant will allow us to keep DECIPHER up to date with best practice and emerging opportunities in clinical interpretation as the landscape evolves.
The grant also provides for a transition of DECIPHER's hosting and development from the Wellcome Sanger Institute (where DECIPHER began and has been based for the last 17 years) to the European Bioinformatics Institute (EMBL-EBI; https://www.ebi.ac.uk), which runs Ensembl and its Variant Effect Predictor (VEP), Gene2Phenotype and many other resources which are critical to DECIPHER's work. It is intended that the team will move in April 2022. Co-PI Helen Firth will remain the clinical lead; Matt Hurles will step back as co-PI but will remain involved as a collaborator and Fiona Cunningham, who leads EBI's Genome Interpretation Team, will join as co-PI. Both institutes are committed to a smooth transition and the migration will not involve any changes to the address (URL), the appearance, or the functionality of DECIPHER.
The Deciphering Developmental Disorders (DDD) project (https://www.ddduk.org), which has recruited nearly 14,000 families in the UK and Ireland, will still deliver results through DECIPHER, while the research work will remain at Sanger. We expect to provide further information on the arrangements to DECIPHER depositors closer to the time of the move.
DECIPHER v11.8 Released
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You can also view this on the web at: https://www.deciphergenomics.org/about/news
It is now possible to search for information about single sequence and protein variants. DNA sequence variant search supports searching by GRCh38 location, by SPDI, HGVSg or Ensembl stable IDs, in addition to HGVSc plus HGNC gene symbol or Refseq transcript. Protein variant search supports searching by HGVSp (single letter or trigraph) plus HGNC gene symbol of Refseq transcript. Searching for sequence variants now takes you to a dedicated sequence variant page, which displays information relevant to that variant. The following page provides information on a missense variant in SPOP: https://www.deciphergenomics.org/sequence-variant/17-49619031-C-T/patient-o…. Searching for protein variants takes you to a dedicated protein variant page, which displays information relevant to that protein change. The following page provides information on a Arginine to Tryptophan change in PACS1: https://www.deciphergenomics.org/protein-variant/ENSG00000175115-203-R-W/pr…
A new Clinvar annotation tab is available on patient variant, sequence variant and protein variant pages. This tab contains information about ClinVar assertions. In this example, the variant has 0, 1 and 2 star ClinVar assertions: https://www.deciphergenomics.org/protein-variant/ENSG00000175115-203-R-W/an…
It is now possible for depositors to record mosaicism by tissue, for mosaic UPD variants.
Optional DECIPHER ClinVar submission
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DECIPHER now supports the deposition of variant data to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar) to enable the greater sharing and aggregation of variant data globally. Submission is optional and the coordinator(s) of a DECIPHER project must approve ClinVar deposition before DECIPHER will deposit data to ClinVar on their behalf.
DECIPHER will only deposit variant data from openly shared patient records, for which explicit patient consent for open sharing has been recorded in DECIPHER. Only openly shared data will be included in the submission. DECIPHER will deposit variant information and high level phenotype information, in addition to a link to the relevant DECIPHER patient record.
If you are interested in DECIPHER submitting the openly consented data in your project to ClinVar, please speak with the coordinator(s) of the project at your centre and/or contact us at contact(a)deciphergenomics.org<mailto:contact@deciphergenomics.org>
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We look forward to your feedback and suggestions for improvement. Please use the "Feedback" button which is available on every page and fill in the simple form to get in touch with us. Your details will be filled in automatically if you are logged in.
Best Regards
Julia, on behalf of the DECIPHER team
Julia Foreman PhD
DECIPHER Project Manager
Email: contact(a)deciphergenomics.org
Web: https://www.deciphergenomics.org
Twitter: @decipher_wtsi
Dear All,
Greetings from a warm and hazy East Anglia.
In this update:
- DECIPHER v11.6 Released
- Optional DECIPHER ClinVar submission
DECIPHER v11.6 Released
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You can also view this on the web at: https://www.deciphergenomics.org/about/news
It is now possible to query Matchmaker Exchange (https://www.matchmakerexchange.org/) through DECIPHER to find matches for small copy-number variants that overlap a gene, in addition to sequence variants. Matchmaker exchange allows the federated discovery of potential matching patients in connected databases. DECIPHER currently supports the searching for patient matches in PhenomeCentral, MyGene2, GeneMatcher, RD-Connect and Broad-seqr. When DECIPHER users query Matchmaker Exchange, overlapping phenotypes are now highlighted in the interface to enable relevant patient matches to more easily be identified.
On plots of individual patients' height, weight, and head circumference (visible to depositors who enter this information), the points representing individual observations are now connected with curves instead of lines, to better approximate the likely pattern of growth.
The genome browser tracks menu has been updated so that the available tracks are grouped to allow users to more easily find tracks of interest. The tracks menu can be accessed by clicking on the word "Tracks" in the top left of the genome browser.
It is now possible for DECIPHER depositors to copy a patient's phenotypes and associated HPO codes. Click on "Show simple term list" to view this information (this is only visible for patients in your own projects). This development helps enable interfacing with electronic health records and family tree programs.
Optional DECIPHER ClinVar submission
=============
DECIPHER will soon support the deposition of variant data to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) to enable the greater sharing and aggregation of variant data globally. Submission is optional and the coordinator(s) of a DECIPHER project must approve ClinVar deposition before DECIPHER will deposit data to ClinVar on their behalf.
DECIPHER will only deposit variant data from openly shared patient records, for which explicit patient consent for open sharing has been recorded in DECIPHER. Only openly shared data will be included in the submission. DECIPHER will deposit variant information and high level phenotype information, in addition to a link to the relevant DECIPHER patient record.
If you are interested in DECIPHER submitting the openly consented data in your project to ClinVar, please speak with the coordinator(s) of the project at your centre and/or contact us at contact(a)deciphergenomics.org
=============
We look forward to your feedback and suggestions for improvement. Please use the "Feedback" button which is available on every page and fill in the simple form to get in touch with us. Your details will be filled in automatically if you are logged in.
Best Regards
Julia, on behalf of the DECIPHER team
Julia Foreman PhD
DECIPHER Project Manager
Email: contact(a)deciphergenomics.org
Web: https://www.deciphergenomics.org
Twitter: @decipher_wtsi
