SlideShare a Scribd company logo
The Transforming Genetic
Medicine Initiative (TGMI)
£5.3M 4 year programme funded by
Wellcome
Designing, Developing and
Delivering Integrated Foundations
for Genetic Medicine
Nazneen Rahman
Paul Flicek Caroline Wright
Sian Ellard David Fitzpatrick
Ewan Birney
Fiona Cunningham
Graeme BlackHelen Firth
Gerton Lunter
Matthew Hurles
Patrick Chinnery
TGMI PIs
National and international collaborations
Transforming genetic medicine
Must ensure the wealth of existing medical
genetic knowledge informs our use of current
and future technology, if we are to do more
right and less wrong.
‘The past is never dead, it’s not even past.’ William Faulkner
GENOME PHENOME
Genomic medicine
GENOME PHENOME
TGMI is focussed on genes
GENE ‘MENDELIAN’
DISORDERS
Genetic medicine 1990-2010
GENE ‘MENDELIAN’
DISORDERS
Prior to NGS, genetic medicine was phenotype-driven.
Meticulous phenotyping used to decide which genes to test.
Genetic medicine 2020
GENE ‘MENDELIAN’
DISORDERS
With NGS, genetic medicine becomes genotype-driven and
can potentially be large-scale and routine.
Genetic medicine 2010-2016
GENE ‘MENDELIAN’
DISORDERS
With NGS, genetic medicine can be genotype-driven. But as
the processes are not well formed phenotyping often used
(often incorrectly) to decide which data is ‘relevant’.
TGMI aims to undertake conceptual,
foundational research to deliver
practical solutions to make genetic
medicine work
TGMI Aims
1. To provide robust, comprehensive information on
links between genes and human disease in a user-
friendly interface.
2. To develop standardised frameworks for consistent
clinical annotation and reporting of gene variation.
3. To develop approaches to deliver fast, automated,
high-throughput, large-scale variant interpretation.
4. To develop and validate flexible, multipurpose
analytical processes to maximise clinical and research
utilities of genetic testing.
GENES
Gene 1
Gene 20,000
For each gene ask qn:
Are germline mutations known to
‘cause’ a human disorder
YES – red (should not become
blue)
NO – blue (some will become
red)
All others – grey (further work
to classify to red or blue)
Gene Disease Map
DISEASES
Many complexities
at phenotype level.
‘Mendelian’
diseases
Why this is needed
Q: How many disease genes are there?
A: Depends who and how you ask.
OMIM: ‘genes phenotype-causing mutation’ = 3416
‘phenotype description, molecular basis known’ = 4482
BioMart: Ensembl Genes: + Swiss Prot IDs and OMIM
phenotype = 3268
Gene Cards: ‘disease genes’ = 9578
TGMI Aims
1. To provide robust, comprehensive information on
links between genes and human disease in a user-
friendly interface.
2. To develop standardised frameworks for consistent
clinical annotation and reporting of gene variation.
3. To develop approaches to deliver fast, automated,
high-throughput, large-scale variant interpretation.
4. To develop and validate flexible, multipurpose
analytical processes to maximise clinical and research
utilities of genetic testing.
TGMI – Aim 2
2.1 – Defining a Clinical Annotation Reference
System (CARS)
2.2 – Defining a Clinical Sequencing Notation
(CSN)
2.3 – Development and distribution of
conversion tools
Why this is needed
• In the clinic and research settings there is
huge variability in annotation of genetic
variation at every level (gene name, transcript
choice, variant annotation etc).
• This inevitably compromises data integration,
and clinical utility and fosters errors and
harms.
The CARS
• The Clinical Annotation Reference System
(CARS) encompasses the set of protein-coding
genes, the set of reference transcripts and
proteins corresponding to the genes, and a
Clinical Sequencing Notation (CSN) for
annotation of variation according to the
sequences.
• Defined against the reference human
genome.
TGMI gene set working criteria
• Has an HGNC ID
• Has an annotated start (which can be non-
methionine)
• Has an annotated stop
• Occurs on chromosomes 1-22, X, Y, or MT
• Has a gene and transcript biotype of “protein-
coding” from Ensembl (release 84)
The TGMI gene working set is
comprised of 18,885 genes
Clinical reference transcripts
1. Sequences must be based on the reference human
genome.
2. The system must allow flexible iteration without
compromising stability or clarity of sequence selection.
3. Reference transcripts must have durability, i.e. historical
sequences used for clinical reporting that are
subsequently superseded must remain available.
4. The reference transcript set should include as few
sequences as possible (one per gene for most genes) but
as many as required.
5. The reference transcript set must be easily available and
usable to encourage universal uptake.
CSN – Clinical Sequencing Notation
• Once transcript is selected, the observed variant
must be named according to its relative difference
from the reference.
• Fixed, standardised, automatic process for
annotation of sequence variation
• Consistent with historical HGVS guidelines
TGMI Aims
1. To provide robust, comprehensive information on
links between genes and human disease in a user-
friendly interface.
2. To develop standardised frameworks for consistent
clinical annotation and reporting of gene variation.
3. To develop approaches to deliver fast, automated,
high-throughput, large-scale variant interpretation.
4. To develop and validate flexible, multipurpose
analytical processes to maximise clinical and research
utilities of genetic testing.
Traditional interpretation process
1. Leveraging generic predictors, e.g. evolutionary
conservation, protein structural features, impact on
splicing etc to predict the functional consequences
of individual variants (done in lab).
2. Leveraging expert assessment of clinical impact
through disease and gene specific knowledge about
the phenotype, genetic architecture, genotype-
phenotype correlations, personal and family history
and variant segregation etc (done in clinic).
Interpretation requirements
1. High-throughput + large volume
2. Fast turnaround
3. Integrated into NGS pipelines
4. Integrated into clinical pipelines
5. Intelligible and usable by non-expert/patients
Variant Phenotype
Variant Phenotype
Frequency of phenotype
Mechanism of pathogenicity
Inheritance pattern
Attribution of gene for
phenotype
Penetrance of gene for
phenotype
Population variation
Variability of gene
Gene structure/function
Much useful information can be utilised and automated so
that the required manual curation can be focussed on the
~2-5% of variants where it is required.
TGMI Aims
1. To provide robust, comprehensive information on
links between genes and human disease in a user-
friendly interface.
2. To develop standardised frameworks for consistent
clinical annotation and reporting of gene variation.
3. To develop approaches to deliver fast, automated,
high-throughput, large-scale variant interpretation.
4. To develop and validate flexible, multipurpose
analytical processes to maximise clinical and research
utilities of genetic testing.
OpEx (Optimised Exome) pipeline
https://github.com/RahmanTeam/OpEx
www.icr.ac.uk/opex
OpEx pipeline
•Simple
•To clinical standards
•High-quality indel calling
http://icr.ac.uk/opex
https://github.com/RahmanTeam/OpEx
• Comparisons with ExAC
• Comparisons with clinical
exome pipelines
All input is welcome!
• The TGMI is keen to hear from and engage with anyone
interested in our aims. We are grateful for any input into
what is needed in genetic medicine, how those needs are
best met, and whether our solutions work.
• How to stay in touch:
– http://theTGMI.org
– info@theTGMI.org
– Weekly blog
– Twitter: @theTGMI

More Related Content

What's hot

2016 ashg giab poster
2016 ashg giab poster2016 ashg giab poster
2016 ashg giab poster
GenomeInABottle
 
2017 agbt giab_poster
2017 agbt giab_poster2017 agbt giab_poster
2017 agbt giab_poster
GenomeInABottle
 
GIAB-GRC workshop oct2015 giab introduction 151005
GIAB-GRC workshop oct2015 giab introduction 151005GIAB-GRC workshop oct2015 giab introduction 151005
GIAB-GRC workshop oct2015 giab introduction 151005
GenomeInABottle
 
161115 precision fda giab
161115 precision fda giab161115 precision fda giab
161115 precision fda giab
GenomeInABottle
 
Aug2013 illumina platinum genomes
Aug2013 illumina platinum genomesAug2013 illumina platinum genomes
Aug2013 illumina platinum genomes
GenomeInABottle
 
GIAB Sep2016 Lightning megan cleveland targeted seq
GIAB Sep2016 Lightning megan cleveland targeted seqGIAB Sep2016 Lightning megan cleveland targeted seq
GIAB Sep2016 Lightning megan cleveland targeted seq
GenomeInABottle
 
171114 best practices for benchmarking variant calls justin
171114 best practices for benchmarking variant calls justin171114 best practices for benchmarking variant calls justin
171114 best practices for benchmarking variant calls justin
GenomeInABottle
 
Aug2015 horizon diagnostics
Aug2015 horizon diagnosticsAug2015 horizon diagnostics
Aug2015 horizon diagnostics
GenomeInABottle
 
Tools for Using NIST Reference Materials
Tools for Using NIST Reference MaterialsTools for Using NIST Reference Materials
Tools for Using NIST Reference Materials
GenomeInABottle
 
Aug2015 salit standards architecture
Aug2015 salit standards architectureAug2015 salit standards architecture
Aug2015 salit standards architecture
GenomeInABottle
 
Giab aug2015 intro and update 150821.pptx
Giab aug2015 intro and update 150821.pptxGiab aug2015 intro and update 150821.pptx
Giab aug2015 intro and update 150821.pptx
GenomeInABottle
 
Genome in a Bottle- reference materials to benchmark challenging variants and...
Genome in a Bottle- reference materials to benchmark challenging variants and...Genome in a Bottle- reference materials to benchmark challenging variants and...
Genome in a Bottle- reference materials to benchmark challenging variants and...
GenomeInABottle
 
Aug2013 NIST highly confident genotype calls for NA12878
Aug2013 NIST highly confident genotype calls for NA12878Aug2013 NIST highly confident genotype calls for NA12878
Aug2013 NIST highly confident genotype calls for NA12878
GenomeInABottle
 
ASHG 2015 Genome in a bottle
ASHG 2015 Genome in a bottleASHG 2015 Genome in a bottle
ASHG 2015 Genome in a bottle
GenomeInABottle
 
Aug2015 Giab nist integration methods
Aug2015 Giab nist integration methodsAug2015 Giab nist integration methods
Aug2015 Giab nist integration methods
GenomeInABottle
 
Jan2016 horizon GIAB
Jan2016 horizon GIABJan2016 horizon GIAB
Jan2016 horizon GIAB
GenomeInABottle
 
Aug2015 Ali Bashir and Jason Chin Pac bio giab_assembly_summary_ali3
Aug2015 Ali Bashir and Jason Chin Pac bio giab_assembly_summary_ali3Aug2015 Ali Bashir and Jason Chin Pac bio giab_assembly_summary_ali3
Aug2015 Ali Bashir and Jason Chin Pac bio giab_assembly_summary_ali3
GenomeInABottle
 
2017 amp benchmarking_poster_justin
2017 amp benchmarking_poster_justin2017 amp benchmarking_poster_justin
2017 amp benchmarking_poster_justin
GenomeInABottle
 
Genome in a bottle for next gen dx v2 180821
Genome in a bottle for next gen dx v2 180821Genome in a bottle for next gen dx v2 180821
Genome in a bottle for next gen dx v2 180821
GenomeInABottle
 
160627 giab for festival sv workshop
160627 giab for festival sv workshop160627 giab for festival sv workshop
160627 giab for festival sv workshop
GenomeInABottle
 

What's hot (20)

2016 ashg giab poster
2016 ashg giab poster2016 ashg giab poster
2016 ashg giab poster
 
2017 agbt giab_poster
2017 agbt giab_poster2017 agbt giab_poster
2017 agbt giab_poster
 
GIAB-GRC workshop oct2015 giab introduction 151005
GIAB-GRC workshop oct2015 giab introduction 151005GIAB-GRC workshop oct2015 giab introduction 151005
GIAB-GRC workshop oct2015 giab introduction 151005
 
161115 precision fda giab
161115 precision fda giab161115 precision fda giab
161115 precision fda giab
 
Aug2013 illumina platinum genomes
Aug2013 illumina platinum genomesAug2013 illumina platinum genomes
Aug2013 illumina platinum genomes
 
GIAB Sep2016 Lightning megan cleveland targeted seq
GIAB Sep2016 Lightning megan cleveland targeted seqGIAB Sep2016 Lightning megan cleveland targeted seq
GIAB Sep2016 Lightning megan cleveland targeted seq
 
171114 best practices for benchmarking variant calls justin
171114 best practices for benchmarking variant calls justin171114 best practices for benchmarking variant calls justin
171114 best practices for benchmarking variant calls justin
 
Aug2015 horizon diagnostics
Aug2015 horizon diagnosticsAug2015 horizon diagnostics
Aug2015 horizon diagnostics
 
Tools for Using NIST Reference Materials
Tools for Using NIST Reference MaterialsTools for Using NIST Reference Materials
Tools for Using NIST Reference Materials
 
Aug2015 salit standards architecture
Aug2015 salit standards architectureAug2015 salit standards architecture
Aug2015 salit standards architecture
 
Giab aug2015 intro and update 150821.pptx
Giab aug2015 intro and update 150821.pptxGiab aug2015 intro and update 150821.pptx
Giab aug2015 intro and update 150821.pptx
 
Genome in a Bottle- reference materials to benchmark challenging variants and...
Genome in a Bottle- reference materials to benchmark challenging variants and...Genome in a Bottle- reference materials to benchmark challenging variants and...
Genome in a Bottle- reference materials to benchmark challenging variants and...
 
Aug2013 NIST highly confident genotype calls for NA12878
Aug2013 NIST highly confident genotype calls for NA12878Aug2013 NIST highly confident genotype calls for NA12878
Aug2013 NIST highly confident genotype calls for NA12878
 
ASHG 2015 Genome in a bottle
ASHG 2015 Genome in a bottleASHG 2015 Genome in a bottle
ASHG 2015 Genome in a bottle
 
Aug2015 Giab nist integration methods
Aug2015 Giab nist integration methodsAug2015 Giab nist integration methods
Aug2015 Giab nist integration methods
 
Jan2016 horizon GIAB
Jan2016 horizon GIABJan2016 horizon GIAB
Jan2016 horizon GIAB
 
Aug2015 Ali Bashir and Jason Chin Pac bio giab_assembly_summary_ali3
Aug2015 Ali Bashir and Jason Chin Pac bio giab_assembly_summary_ali3Aug2015 Ali Bashir and Jason Chin Pac bio giab_assembly_summary_ali3
Aug2015 Ali Bashir and Jason Chin Pac bio giab_assembly_summary_ali3
 
2017 amp benchmarking_poster_justin
2017 amp benchmarking_poster_justin2017 amp benchmarking_poster_justin
2017 amp benchmarking_poster_justin
 
Genome in a bottle for next gen dx v2 180821
Genome in a bottle for next gen dx v2 180821Genome in a bottle for next gen dx v2 180821
Genome in a bottle for next gen dx v2 180821
 
160627 giab for festival sv workshop
160627 giab for festival sv workshop160627 giab for festival sv workshop
160627 giab for festival sv workshop
 

Viewers also liked

Variation reference graphs and the variation graph toolkit vg
Variation reference graphs and the variation graph toolkit vgVariation reference graphs and the variation graph toolkit vg
Variation reference graphs and the variation graph toolkit vg
Genome Reference Consortium
 
Graph and assembly strategies for the MHC and ribosomal DNA regions
Graph and assembly strategies for the MHC and ribosomal DNA regionsGraph and assembly strategies for the MHC and ribosomal DNA regions
Graph and assembly strategies for the MHC and ribosomal DNA regions
Genome Reference Consortium
 
agbt 2016 workshop lindsay
agbt 2016 workshop lindsayagbt 2016 workshop lindsay
agbt 2016 workshop lindsay
Genome Reference Consortium
 
Getting the most from the reference assembly
Getting the most from the reference assemblyGetting the most from the reference assembly
Getting the most from the reference assembly
Genome Reference Consortium
 
Creating Reference-Grade Human Genome Assemblies
Creating Reference-Grade Human Genome AssembliesCreating Reference-Grade Human Genome Assemblies
Creating Reference-Grade Human Genome Assemblies
Genome Reference Consortium
 
Understanding the reference assembly: CSHL Hackathon
Understanding the reference assembly: CSHL HackathonUnderstanding the reference assembly: CSHL Hackathon
Understanding the reference assembly: CSHL Hackathon
Genome Reference Consortium
 
Everyday de novo diploid assembly
Everyday de novo diploid assemblyEveryday de novo diploid assembly
Everyday de novo diploid assembly
Genome Reference Consortium
 
Haplotype resolved structural variation assembly with long reads
Haplotype resolved structural variation assembly with long readsHaplotype resolved structural variation assembly with long reads
Haplotype resolved structural variation assembly with long reads
Genome Reference Consortium
 
AGBT2017 Reference Workshop: Schneider
AGBT2017 Reference Workshop: SchneiderAGBT2017 Reference Workshop: Schneider
AGBT2017 Reference Workshop: Schneider
Genome Reference Consortium
 
AGBT2017 Reference Workshop: Lindsay
AGBT2017 Reference Workshop: LindsayAGBT2017 Reference Workshop: Lindsay
AGBT2017 Reference Workshop: Lindsay
Genome Reference Consortium
 
AGBT2017 Reference Workshop: Fulton
AGBT2017 Reference Workshop: FultonAGBT2017 Reference Workshop: Fulton
AGBT2017 Reference Workshop: Fulton
Genome Reference Consortium
 
Creating Reference-Grade Human Genome Assemblies
Creating Reference-Grade Human Genome AssembliesCreating Reference-Grade Human Genome Assemblies
Creating Reference-Grade Human Genome Assemblies
Genome Reference Consortium
 
Exploiting long read sequencing technology to build a substantially improved ...
Exploiting long read sequencing technology to build a substantially improved ...Exploiting long read sequencing technology to build a substantially improved ...
Exploiting long read sequencing technology to build a substantially improved ...
Genome Reference Consortium
 
Everyday de novo assembly
Everyday de novo assemblyEveryday de novo assembly
Everyday de novo assembly
Genome Reference Consortium
 
AGBT 2016 Workshop Magrini
AGBT 2016 Workshop MagriniAGBT 2016 Workshop Magrini
AGBT 2016 Workshop Magrini
Genome Reference Consortium
 
ClinVar: Getting the most from the reference assembly and reference materials
ClinVar: Getting the most from the reference assembly and reference materialsClinVar: Getting the most from the reference assembly and reference materials
ClinVar: Getting the most from the reference assembly and reference materials
Genome Reference Consortium
 
TAGC2016 schneider
TAGC2016 schneiderTAGC2016 schneider
TAGC2016 schneider
Genome Reference Consortium
 
agbt 2016 workshop church
agbt 2016 workshop churchagbt 2016 workshop church
agbt 2016 workshop church
Genome Reference Consortium
 

Viewers also liked (18)

Variation reference graphs and the variation graph toolkit vg
Variation reference graphs and the variation graph toolkit vgVariation reference graphs and the variation graph toolkit vg
Variation reference graphs and the variation graph toolkit vg
 
Graph and assembly strategies for the MHC and ribosomal DNA regions
Graph and assembly strategies for the MHC and ribosomal DNA regionsGraph and assembly strategies for the MHC and ribosomal DNA regions
Graph and assembly strategies for the MHC and ribosomal DNA regions
 
agbt 2016 workshop lindsay
agbt 2016 workshop lindsayagbt 2016 workshop lindsay
agbt 2016 workshop lindsay
 
Getting the most from the reference assembly
Getting the most from the reference assemblyGetting the most from the reference assembly
Getting the most from the reference assembly
 
Creating Reference-Grade Human Genome Assemblies
Creating Reference-Grade Human Genome AssembliesCreating Reference-Grade Human Genome Assemblies
Creating Reference-Grade Human Genome Assemblies
 
Understanding the reference assembly: CSHL Hackathon
Understanding the reference assembly: CSHL HackathonUnderstanding the reference assembly: CSHL Hackathon
Understanding the reference assembly: CSHL Hackathon
 
Everyday de novo diploid assembly
Everyday de novo diploid assemblyEveryday de novo diploid assembly
Everyday de novo diploid assembly
 
Haplotype resolved structural variation assembly with long reads
Haplotype resolved structural variation assembly with long readsHaplotype resolved structural variation assembly with long reads
Haplotype resolved structural variation assembly with long reads
 
AGBT2017 Reference Workshop: Schneider
AGBT2017 Reference Workshop: SchneiderAGBT2017 Reference Workshop: Schneider
AGBT2017 Reference Workshop: Schneider
 
AGBT2017 Reference Workshop: Lindsay
AGBT2017 Reference Workshop: LindsayAGBT2017 Reference Workshop: Lindsay
AGBT2017 Reference Workshop: Lindsay
 
AGBT2017 Reference Workshop: Fulton
AGBT2017 Reference Workshop: FultonAGBT2017 Reference Workshop: Fulton
AGBT2017 Reference Workshop: Fulton
 
Creating Reference-Grade Human Genome Assemblies
Creating Reference-Grade Human Genome AssembliesCreating Reference-Grade Human Genome Assemblies
Creating Reference-Grade Human Genome Assemblies
 
Exploiting long read sequencing technology to build a substantially improved ...
Exploiting long read sequencing technology to build a substantially improved ...Exploiting long read sequencing technology to build a substantially improved ...
Exploiting long read sequencing technology to build a substantially improved ...
 
Everyday de novo assembly
Everyday de novo assemblyEveryday de novo assembly
Everyday de novo assembly
 
AGBT 2016 Workshop Magrini
AGBT 2016 Workshop MagriniAGBT 2016 Workshop Magrini
AGBT 2016 Workshop Magrini
 
ClinVar: Getting the most from the reference assembly and reference materials
ClinVar: Getting the most from the reference assembly and reference materialsClinVar: Getting the most from the reference assembly and reference materials
ClinVar: Getting the most from the reference assembly and reference materials
 
TAGC2016 schneider
TAGC2016 schneiderTAGC2016 schneider
TAGC2016 schneider
 
agbt 2016 workshop church
agbt 2016 workshop churchagbt 2016 workshop church
agbt 2016 workshop church
 

Similar to The Transforming Genetic Medicine Initiative (TGMI)

PadminiNarayanan-Intro-2018.pptx
PadminiNarayanan-Intro-2018.pptxPadminiNarayanan-Intro-2018.pptx
PadminiNarayanan-Intro-2018.pptx
DESMONDEZIEKE1
 
multiomics-ebook.pdf
multiomics-ebook.pdfmultiomics-ebook.pdf
multiomics-ebook.pdf
Nusrat Gulbarga
 
INBIOMEDvision Workshop at MIE 2011. Victoria López
INBIOMEDvision Workshop at MIE 2011. Victoria LópezINBIOMEDvision Workshop at MIE 2011. Victoria López
INBIOMEDvision Workshop at MIE 2011. Victoria López
INBIOMEDvision
 
Accelerating the benefits of genomics worldwide
Accelerating the benefits of genomics worldwideAccelerating the benefits of genomics worldwide
Accelerating the benefits of genomics worldwide
Joaquin Dopazo
 
NGS and the molecular basis of disease: a practical view
NGS and the molecular basis of disease: a practical viewNGS and the molecular basis of disease: a practical view
NGS and the molecular basis of disease: a practical view
Vall d'Hebron Institute of Research (VHIR)
 
Dalton
DaltonDalton
Dalton presentation
Dalton presentationDalton presentation
EuroBioForum2014_speaker_Manolio
EuroBioForum2014_speaker_ManolioEuroBioForum2014_speaker_Manolio
EuroBioForum2014_speaker_Manolio
EuroBioForum
 
IRIDA's Genomic epidemiology application ontology (GenEpiO): Genomic, clinica...
IRIDA's Genomic epidemiology application ontology (GenEpiO): Genomic, clinica...IRIDA's Genomic epidemiology application ontology (GenEpiO): Genomic, clinica...
IRIDA's Genomic epidemiology application ontology (GenEpiO): Genomic, clinica...
Emma Griffiths
 
Gen epio immem_griffiths
Gen epio immem_griffithsGen epio immem_griffiths
Gen epio immem_griffiths
IRIDA_community
 
Grand round whsiao_may2015
Grand round whsiao_may2015Grand round whsiao_may2015
Grand round whsiao_may2015
IRIDA_community
 
How Can We Make Genomic Epidemiology a Widespread Reality? - William Hsiao
How Can We Make Genomic Epidemiology a Widespread Reality?  - William HsiaoHow Can We Make Genomic Epidemiology a Widespread Reality?  - William Hsiao
How Can We Make Genomic Epidemiology a Widespread Reality? - William Hsiao
William Hsiao
 
Genomics and proteomics by shreeman
Genomics and proteomics by shreemanGenomics and proteomics by shreeman
Genomics and proteomics by shreeman
shreeman cs
 
Open Frame Sequencing™
Open Frame Sequencing™ Open Frame Sequencing™
Open Frame Sequencing™
INVICTA GENETICS
 
Reg Sci Lecture Dec 2016
Reg Sci Lecture Dec 2016Reg Sci Lecture Dec 2016
Reg Sci Lecture Dec 2016
Rick Silva
 
A Retrospective Analysis of Exome Sequencing Cases Using the GenePool™ Genomi...
A Retrospective Analysis of Exome Sequencing Cases Using the GenePool™ Genomi...A Retrospective Analysis of Exome Sequencing Cases Using the GenePool™ Genomi...
A Retrospective Analysis of Exome Sequencing Cases Using the GenePool™ Genomi...
Antoaneta Vladimirova
 
Gene hunting strategies
Gene hunting strategiesGene hunting strategies
Gene hunting strategies
Ashfaq Ahmad
 
Human genome project ()
Human genome project ()Human genome project ()
Human genome project ()
Tapeshwar Yadav
 
How to transform genomic big data into valuable clinical information
How to transform genomic big data into valuable clinical informationHow to transform genomic big data into valuable clinical information
How to transform genomic big data into valuable clinical information
Joaquin Dopazo
 
171017 giab for giab grc workshop
171017 giab for giab grc workshop171017 giab for giab grc workshop
171017 giab for giab grc workshop
Genome Reference Consortium
 

Similar to The Transforming Genetic Medicine Initiative (TGMI) (20)

PadminiNarayanan-Intro-2018.pptx
PadminiNarayanan-Intro-2018.pptxPadminiNarayanan-Intro-2018.pptx
PadminiNarayanan-Intro-2018.pptx
 
multiomics-ebook.pdf
multiomics-ebook.pdfmultiomics-ebook.pdf
multiomics-ebook.pdf
 
INBIOMEDvision Workshop at MIE 2011. Victoria López
INBIOMEDvision Workshop at MIE 2011. Victoria LópezINBIOMEDvision Workshop at MIE 2011. Victoria López
INBIOMEDvision Workshop at MIE 2011. Victoria López
 
Accelerating the benefits of genomics worldwide
Accelerating the benefits of genomics worldwideAccelerating the benefits of genomics worldwide
Accelerating the benefits of genomics worldwide
 
NGS and the molecular basis of disease: a practical view
NGS and the molecular basis of disease: a practical viewNGS and the molecular basis of disease: a practical view
NGS and the molecular basis of disease: a practical view
 
Dalton
DaltonDalton
Dalton
 
Dalton presentation
Dalton presentationDalton presentation
Dalton presentation
 
EuroBioForum2014_speaker_Manolio
EuroBioForum2014_speaker_ManolioEuroBioForum2014_speaker_Manolio
EuroBioForum2014_speaker_Manolio
 
IRIDA's Genomic epidemiology application ontology (GenEpiO): Genomic, clinica...
IRIDA's Genomic epidemiology application ontology (GenEpiO): Genomic, clinica...IRIDA's Genomic epidemiology application ontology (GenEpiO): Genomic, clinica...
IRIDA's Genomic epidemiology application ontology (GenEpiO): Genomic, clinica...
 
Gen epio immem_griffiths
Gen epio immem_griffithsGen epio immem_griffiths
Gen epio immem_griffiths
 
Grand round whsiao_may2015
Grand round whsiao_may2015Grand round whsiao_may2015
Grand round whsiao_may2015
 
How Can We Make Genomic Epidemiology a Widespread Reality? - William Hsiao
How Can We Make Genomic Epidemiology a Widespread Reality?  - William HsiaoHow Can We Make Genomic Epidemiology a Widespread Reality?  - William Hsiao
How Can We Make Genomic Epidemiology a Widespread Reality? - William Hsiao
 
Genomics and proteomics by shreeman
Genomics and proteomics by shreemanGenomics and proteomics by shreeman
Genomics and proteomics by shreeman
 
Open Frame Sequencing™
Open Frame Sequencing™ Open Frame Sequencing™
Open Frame Sequencing™
 
Reg Sci Lecture Dec 2016
Reg Sci Lecture Dec 2016Reg Sci Lecture Dec 2016
Reg Sci Lecture Dec 2016
 
A Retrospective Analysis of Exome Sequencing Cases Using the GenePool™ Genomi...
A Retrospective Analysis of Exome Sequencing Cases Using the GenePool™ Genomi...A Retrospective Analysis of Exome Sequencing Cases Using the GenePool™ Genomi...
A Retrospective Analysis of Exome Sequencing Cases Using the GenePool™ Genomi...
 
Gene hunting strategies
Gene hunting strategiesGene hunting strategies
Gene hunting strategies
 
Human genome project ()
Human genome project ()Human genome project ()
Human genome project ()
 
How to transform genomic big data into valuable clinical information
How to transform genomic big data into valuable clinical informationHow to transform genomic big data into valuable clinical information
How to transform genomic big data into valuable clinical information
 
171017 giab for giab grc workshop
171017 giab for giab grc workshop171017 giab for giab grc workshop
171017 giab for giab grc workshop
 

More from Genome Reference Consortium

Previewing GRCm39: Assembly Updates from the GRC
Previewing GRCm39: Assembly Updates from the GRCPreviewing GRCm39: Assembly Updates from the GRC
Previewing GRCm39: Assembly Updates from the GRC
Genome Reference Consortium
 
What's new and what's next for the human reference assembly?
What's new and what's next for the human reference assembly?What's new and what's next for the human reference assembly?
What's new and what's next for the human reference assembly?
Genome Reference Consortium
 
Advancements in the human genome reference assembly (GRCh38)
Advancements in the human genome reference assembly (GRCh38)Advancements in the human genome reference assembly (GRCh38)
Advancements in the human genome reference assembly (GRCh38)
Genome Reference Consortium
 
Telomere-to-telomere assembly of a complete human chromosomes
Telomere-to-telomere assembly of a complete human chromosomesTelomere-to-telomere assembly of a complete human chromosomes
Telomere-to-telomere assembly of a complete human chromosomes
Genome Reference Consortium
 
Genome variation graphs with the vg toolkit
Genome variation graphs with the vg toolkitGenome variation graphs with the vg toolkit
Genome variation graphs with the vg toolkit
Genome Reference Consortium
 
The Matched Annotation from NCBI and EMBL-EBI (MANE) Project
The Matched Annotation from NCBI and EMBL-EBI (MANE) ProjectThe Matched Annotation from NCBI and EMBL-EBI (MANE) Project
The Matched Annotation from NCBI and EMBL-EBI (MANE) Project
Genome Reference Consortium
 
Why graph genome storage and updating wakes me up at 4 am
Why graph genome storage and updating wakes me up at 4 amWhy graph genome storage and updating wakes me up at 4 am
Why graph genome storage and updating wakes me up at 4 am
Genome Reference Consortium
 
Schneider grc workshop_final
Schneider grc workshop_finalSchneider grc workshop_final
Schneider grc workshop_final
Genome Reference Consortium
 
Mane v2 final
Mane v2 finalMane v2 final
Lrg and mane 16 oct 2018
Lrg and mane   16 oct 2018Lrg and mane   16 oct 2018
Lrg and mane 16 oct 2018
Genome Reference Consortium
 
20181016 grc presentation-pa
20181016 grc presentation-pa20181016 grc presentation-pa
20181016 grc presentation-pa
Genome Reference Consortium
 
2018 1016 trio_binning_ashg_arhie_final
2018 1016 trio_binning_ashg_arhie_final2018 1016 trio_binning_ashg_arhie_final
2018 1016 trio_binning_ashg_arhie_final
Genome Reference Consortium
 
Variation graphs and population assisted genome inference copy
Variation graphs and population assisted genome inference copyVariation graphs and population assisted genome inference copy
Variation graphs and population assisted genome inference copy
Genome Reference Consortium
 
Ashg2017 workshop schneider
Ashg2017 workshop schneiderAshg2017 workshop schneider
Ashg2017 workshop schneider
Genome Reference Consortium
 
Ashg2017 workshop tg
Ashg2017 workshop tgAshg2017 workshop tg
Ashg2017 workshop tg
Genome Reference Consortium
 
Ashg sedlazeck grc_share
Ashg sedlazeck grc_shareAshg sedlazeck grc_share
Ashg sedlazeck grc_share
Genome Reference Consortium
 
101717.kh miga ashg_grc
101717.kh miga ashg_grc101717.kh miga ashg_grc
101717.kh miga ashg_grc
Genome Reference Consortium
 

More from Genome Reference Consortium (17)

Previewing GRCm39: Assembly Updates from the GRC
Previewing GRCm39: Assembly Updates from the GRCPreviewing GRCm39: Assembly Updates from the GRC
Previewing GRCm39: Assembly Updates from the GRC
 
What's new and what's next for the human reference assembly?
What's new and what's next for the human reference assembly?What's new and what's next for the human reference assembly?
What's new and what's next for the human reference assembly?
 
Advancements in the human genome reference assembly (GRCh38)
Advancements in the human genome reference assembly (GRCh38)Advancements in the human genome reference assembly (GRCh38)
Advancements in the human genome reference assembly (GRCh38)
 
Telomere-to-telomere assembly of a complete human chromosomes
Telomere-to-telomere assembly of a complete human chromosomesTelomere-to-telomere assembly of a complete human chromosomes
Telomere-to-telomere assembly of a complete human chromosomes
 
Genome variation graphs with the vg toolkit
Genome variation graphs with the vg toolkitGenome variation graphs with the vg toolkit
Genome variation graphs with the vg toolkit
 
The Matched Annotation from NCBI and EMBL-EBI (MANE) Project
The Matched Annotation from NCBI and EMBL-EBI (MANE) ProjectThe Matched Annotation from NCBI and EMBL-EBI (MANE) Project
The Matched Annotation from NCBI and EMBL-EBI (MANE) Project
 
Why graph genome storage and updating wakes me up at 4 am
Why graph genome storage and updating wakes me up at 4 amWhy graph genome storage and updating wakes me up at 4 am
Why graph genome storage and updating wakes me up at 4 am
 
Schneider grc workshop_final
Schneider grc workshop_finalSchneider grc workshop_final
Schneider grc workshop_final
 
Mane v2 final
Mane v2 finalMane v2 final
Mane v2 final
 
Lrg and mane 16 oct 2018
Lrg and mane   16 oct 2018Lrg and mane   16 oct 2018
Lrg and mane 16 oct 2018
 
20181016 grc presentation-pa
20181016 grc presentation-pa20181016 grc presentation-pa
20181016 grc presentation-pa
 
2018 1016 trio_binning_ashg_arhie_final
2018 1016 trio_binning_ashg_arhie_final2018 1016 trio_binning_ashg_arhie_final
2018 1016 trio_binning_ashg_arhie_final
 
Variation graphs and population assisted genome inference copy
Variation graphs and population assisted genome inference copyVariation graphs and population assisted genome inference copy
Variation graphs and population assisted genome inference copy
 
Ashg2017 workshop schneider
Ashg2017 workshop schneiderAshg2017 workshop schneider
Ashg2017 workshop schneider
 
Ashg2017 workshop tg
Ashg2017 workshop tgAshg2017 workshop tg
Ashg2017 workshop tg
 
Ashg sedlazeck grc_share
Ashg sedlazeck grc_shareAshg sedlazeck grc_share
Ashg sedlazeck grc_share
 
101717.kh miga ashg_grc
101717.kh miga ashg_grc101717.kh miga ashg_grc
101717.kh miga ashg_grc
 

Recently uploaded

Care and Maintenance of Laboratory Equipment in Histotechnology.pptx
Care and Maintenance of Laboratory Equipment in Histotechnology.pptxCare and Maintenance of Laboratory Equipment in Histotechnology.pptx
Care and Maintenance of Laboratory Equipment in Histotechnology.pptx
Dr. Jagroop Singh
 
PCD Pharma Franchise For Gynae Products | Infertility Range - Sarthi Life Sci...
PCD Pharma Franchise For Gynae Products | Infertility Range - Sarthi Life Sci...PCD Pharma Franchise For Gynae Products | Infertility Range - Sarthi Life Sci...
PCD Pharma Franchise For Gynae Products | Infertility Range - Sarthi Life Sci...
Sarthi Life Sciences
 
Operation Theatre Nursing -History of Surgery & Anesthesia.pptx
Operation Theatre Nursing -History of Surgery & Anesthesia.pptxOperation Theatre Nursing -History of Surgery & Anesthesia.pptx
Operation Theatre Nursing -History of Surgery & Anesthesia.pptx
RadhaThapaChhetry
 
POTENTIAL TARGET DISEASES FOR GENE THERAPY SOURAV.pptx
POTENTIAL TARGET DISEASES FOR GENE THERAPY SOURAV.pptxPOTENTIAL TARGET DISEASES FOR GENE THERAPY SOURAV.pptx
POTENTIAL TARGET DISEASES FOR GENE THERAPY SOURAV.pptx
souravpaul769171
 
NUTRICONNECT NEWSLETTER 3RD ISSUE 2ND VOLUME.pdf
NUTRICONNECT NEWSLETTER 3RD ISSUE 2ND VOLUME.pdfNUTRICONNECT NEWSLETTER 3RD ISSUE 2ND VOLUME.pdf
NUTRICONNECT NEWSLETTER 3RD ISSUE 2ND VOLUME.pdf
MatsikoAlex
 
Abnormal CSF Diagnosis and Lumbar puncture
Abnormal CSF Diagnosis and Lumbar punctureAbnormal CSF Diagnosis and Lumbar puncture
Abnormal CSF Diagnosis and Lumbar puncture
Preet Mehta
 
SA Gastro Cure(pancreatic cancer treatment in india).pptx
SA Gastro Cure(pancreatic cancer treatment in india).pptxSA Gastro Cure(pancreatic cancer treatment in india).pptx
SA Gastro Cure(pancreatic cancer treatment in india).pptx
VinothKumar70905
 
Nursing management of patient with peritoneal dialysis
Nursing management of patient with peritoneal dialysisNursing management of patient with peritoneal dialysis
Nursing management of patient with peritoneal dialysis
shivalingatalekar1
 
JULY 2024 Oncology Cartoons by Dr Kanhu Charan Patro
JULY 2024 Oncology Cartoons by Dr Kanhu Charan PatroJULY 2024 Oncology Cartoons by Dr Kanhu Charan Patro
JULY 2024 Oncology Cartoons by Dr Kanhu Charan Patro
Kanhu Charan
 
Introduction to Radiotherapy technology I.pptx
Introduction to Radiotherapy technology I.pptxIntroduction to Radiotherapy technology I.pptx
Introduction to Radiotherapy technology I.pptx
JalalEltabib1
 
Clinical examination of- CRANIAL.- nerves
Clinical examination of- CRANIAL.- nervesClinical examination of- CRANIAL.- nerves
Clinical examination of- CRANIAL.- nerves
DrpoonamHealthclinic
 
Mainstreaming #CleanLanguage in healthcare.pptx
Mainstreaming #CleanLanguage in healthcare.pptxMainstreaming #CleanLanguage in healthcare.pptx
Mainstreaming #CleanLanguage in healthcare.pptx
Judy Rees
 
Abortion pills for sale in Qatar(+919707208804)Buy Cytotec tablet in Doha
Abortion pills for sale in Qatar(+919707208804)Buy Cytotec tablet in DohaAbortion pills for sale in Qatar(+919707208804)Buy Cytotec tablet in Doha
Abortion pills for sale in Qatar(+919707208804)Buy Cytotec tablet in Doha
maishakhanam230
 
Gestational Trophoblastic Disease( GTD)- Molar pregnancy, Gestational Trophob...
Gestational Trophoblastic Disease( GTD)- Molar pregnancy, Gestational Trophob...Gestational Trophoblastic Disease( GTD)- Molar pregnancy, Gestational Trophob...
Gestational Trophoblastic Disease( GTD)- Molar pregnancy, Gestational Trophob...
Dr.Nishant Janu
 
AGARICUS MUSCARIUS.pptx Keynotes by H.C. Allen
AGARICUS MUSCARIUS.pptx  Keynotes by H.C. AllenAGARICUS MUSCARIUS.pptx  Keynotes by H.C. Allen
AGARICUS MUSCARIUS.pptx Keynotes by H.C. Allen
DR.P.S SUDHAKAR
 
Approach to Head Injuiry, Intracranial Pressure Measurement and Management.pptx
Approach to Head Injuiry, Intracranial Pressure Measurement and Management.pptxApproach to Head Injuiry, Intracranial Pressure Measurement and Management.pptx
Approach to Head Injuiry, Intracranial Pressure Measurement and Management.pptx
Bipul Thakur
 
Top 10 Habits for Longevity [Biohacker Summit 2024]
Top 10 Habits for Longevity [Biohacker Summit 2024]Top 10 Habits for Longevity [Biohacker Summit 2024]
Top 10 Habits for Longevity [Biohacker Summit 2024]
Olli Sovijärvi
 
Recognizing and Managing Bacterial Vaginosis.pptx
Recognizing and Managing Bacterial Vaginosis.pptxRecognizing and Managing Bacterial Vaginosis.pptx
Recognizing and Managing Bacterial Vaginosis.pptx
FFragrant
 
Text Book of Critical Care Nursing ICU NURSING
Text Book of Critical Care Nursing  ICU NURSINGText Book of Critical Care Nursing  ICU NURSING
Text Book of Critical Care Nursing ICU NURSING
BP KOIRALA INSTITUTE OF HELATH SCIENCS,, NEPAL
 
Dr Charles James de Vis, M.R.C.S., L.S.A. England, Surgeon to the Charters To...
Dr Charles James de Vis, M.R.C.S., L.S.A. England, Surgeon to the Charters To...Dr Charles James de Vis, M.R.C.S., L.S.A. England, Surgeon to the Charters To...
Dr Charles James de Vis, M.R.C.S., L.S.A. England, Surgeon to the Charters To...
semualkaira
 

Recently uploaded (20)

Care and Maintenance of Laboratory Equipment in Histotechnology.pptx
Care and Maintenance of Laboratory Equipment in Histotechnology.pptxCare and Maintenance of Laboratory Equipment in Histotechnology.pptx
Care and Maintenance of Laboratory Equipment in Histotechnology.pptx
 
PCD Pharma Franchise For Gynae Products | Infertility Range - Sarthi Life Sci...
PCD Pharma Franchise For Gynae Products | Infertility Range - Sarthi Life Sci...PCD Pharma Franchise For Gynae Products | Infertility Range - Sarthi Life Sci...
PCD Pharma Franchise For Gynae Products | Infertility Range - Sarthi Life Sci...
 
Operation Theatre Nursing -History of Surgery & Anesthesia.pptx
Operation Theatre Nursing -History of Surgery & Anesthesia.pptxOperation Theatre Nursing -History of Surgery & Anesthesia.pptx
Operation Theatre Nursing -History of Surgery & Anesthesia.pptx
 
POTENTIAL TARGET DISEASES FOR GENE THERAPY SOURAV.pptx
POTENTIAL TARGET DISEASES FOR GENE THERAPY SOURAV.pptxPOTENTIAL TARGET DISEASES FOR GENE THERAPY SOURAV.pptx
POTENTIAL TARGET DISEASES FOR GENE THERAPY SOURAV.pptx
 
NUTRICONNECT NEWSLETTER 3RD ISSUE 2ND VOLUME.pdf
NUTRICONNECT NEWSLETTER 3RD ISSUE 2ND VOLUME.pdfNUTRICONNECT NEWSLETTER 3RD ISSUE 2ND VOLUME.pdf
NUTRICONNECT NEWSLETTER 3RD ISSUE 2ND VOLUME.pdf
 
Abnormal CSF Diagnosis and Lumbar puncture
Abnormal CSF Diagnosis and Lumbar punctureAbnormal CSF Diagnosis and Lumbar puncture
Abnormal CSF Diagnosis and Lumbar puncture
 
SA Gastro Cure(pancreatic cancer treatment in india).pptx
SA Gastro Cure(pancreatic cancer treatment in india).pptxSA Gastro Cure(pancreatic cancer treatment in india).pptx
SA Gastro Cure(pancreatic cancer treatment in india).pptx
 
Nursing management of patient with peritoneal dialysis
Nursing management of patient with peritoneal dialysisNursing management of patient with peritoneal dialysis
Nursing management of patient with peritoneal dialysis
 
JULY 2024 Oncology Cartoons by Dr Kanhu Charan Patro
JULY 2024 Oncology Cartoons by Dr Kanhu Charan PatroJULY 2024 Oncology Cartoons by Dr Kanhu Charan Patro
JULY 2024 Oncology Cartoons by Dr Kanhu Charan Patro
 
Introduction to Radiotherapy technology I.pptx
Introduction to Radiotherapy technology I.pptxIntroduction to Radiotherapy technology I.pptx
Introduction to Radiotherapy technology I.pptx
 
Clinical examination of- CRANIAL.- nerves
Clinical examination of- CRANIAL.- nervesClinical examination of- CRANIAL.- nerves
Clinical examination of- CRANIAL.- nerves
 
Mainstreaming #CleanLanguage in healthcare.pptx
Mainstreaming #CleanLanguage in healthcare.pptxMainstreaming #CleanLanguage in healthcare.pptx
Mainstreaming #CleanLanguage in healthcare.pptx
 
Abortion pills for sale in Qatar(+919707208804)Buy Cytotec tablet in Doha
Abortion pills for sale in Qatar(+919707208804)Buy Cytotec tablet in DohaAbortion pills for sale in Qatar(+919707208804)Buy Cytotec tablet in Doha
Abortion pills for sale in Qatar(+919707208804)Buy Cytotec tablet in Doha
 
Gestational Trophoblastic Disease( GTD)- Molar pregnancy, Gestational Trophob...
Gestational Trophoblastic Disease( GTD)- Molar pregnancy, Gestational Trophob...Gestational Trophoblastic Disease( GTD)- Molar pregnancy, Gestational Trophob...
Gestational Trophoblastic Disease( GTD)- Molar pregnancy, Gestational Trophob...
 
AGARICUS MUSCARIUS.pptx Keynotes by H.C. Allen
AGARICUS MUSCARIUS.pptx  Keynotes by H.C. AllenAGARICUS MUSCARIUS.pptx  Keynotes by H.C. Allen
AGARICUS MUSCARIUS.pptx Keynotes by H.C. Allen
 
Approach to Head Injuiry, Intracranial Pressure Measurement and Management.pptx
Approach to Head Injuiry, Intracranial Pressure Measurement and Management.pptxApproach to Head Injuiry, Intracranial Pressure Measurement and Management.pptx
Approach to Head Injuiry, Intracranial Pressure Measurement and Management.pptx
 
Top 10 Habits for Longevity [Biohacker Summit 2024]
Top 10 Habits for Longevity [Biohacker Summit 2024]Top 10 Habits for Longevity [Biohacker Summit 2024]
Top 10 Habits for Longevity [Biohacker Summit 2024]
 
Recognizing and Managing Bacterial Vaginosis.pptx
Recognizing and Managing Bacterial Vaginosis.pptxRecognizing and Managing Bacterial Vaginosis.pptx
Recognizing and Managing Bacterial Vaginosis.pptx
 
Text Book of Critical Care Nursing ICU NURSING
Text Book of Critical Care Nursing  ICU NURSINGText Book of Critical Care Nursing  ICU NURSING
Text Book of Critical Care Nursing ICU NURSING
 
Dr Charles James de Vis, M.R.C.S., L.S.A. England, Surgeon to the Charters To...
Dr Charles James de Vis, M.R.C.S., L.S.A. England, Surgeon to the Charters To...Dr Charles James de Vis, M.R.C.S., L.S.A. England, Surgeon to the Charters To...
Dr Charles James de Vis, M.R.C.S., L.S.A. England, Surgeon to the Charters To...
 

The Transforming Genetic Medicine Initiative (TGMI)

  • 1. The Transforming Genetic Medicine Initiative (TGMI) £5.3M 4 year programme funded by Wellcome
  • 2. Designing, Developing and Delivering Integrated Foundations for Genetic Medicine
  • 3. Nazneen Rahman Paul Flicek Caroline Wright Sian Ellard David Fitzpatrick Ewan Birney Fiona Cunningham Graeme BlackHelen Firth Gerton Lunter Matthew Hurles Patrick Chinnery TGMI PIs
  • 4. National and international collaborations
  • 5. Transforming genetic medicine Must ensure the wealth of existing medical genetic knowledge informs our use of current and future technology, if we are to do more right and less wrong. ‘The past is never dead, it’s not even past.’ William Faulkner
  • 7. GENOME PHENOME TGMI is focussed on genes GENE ‘MENDELIAN’ DISORDERS
  • 8. Genetic medicine 1990-2010 GENE ‘MENDELIAN’ DISORDERS Prior to NGS, genetic medicine was phenotype-driven. Meticulous phenotyping used to decide which genes to test.
  • 9. Genetic medicine 2020 GENE ‘MENDELIAN’ DISORDERS With NGS, genetic medicine becomes genotype-driven and can potentially be large-scale and routine.
  • 10. Genetic medicine 2010-2016 GENE ‘MENDELIAN’ DISORDERS With NGS, genetic medicine can be genotype-driven. But as the processes are not well formed phenotyping often used (often incorrectly) to decide which data is ‘relevant’.
  • 11. TGMI aims to undertake conceptual, foundational research to deliver practical solutions to make genetic medicine work
  • 12. TGMI Aims 1. To provide robust, comprehensive information on links between genes and human disease in a user- friendly interface. 2. To develop standardised frameworks for consistent clinical annotation and reporting of gene variation. 3. To develop approaches to deliver fast, automated, high-throughput, large-scale variant interpretation. 4. To develop and validate flexible, multipurpose analytical processes to maximise clinical and research utilities of genetic testing.
  • 13. GENES Gene 1 Gene 20,000 For each gene ask qn: Are germline mutations known to ‘cause’ a human disorder YES – red (should not become blue) NO – blue (some will become red) All others – grey (further work to classify to red or blue) Gene Disease Map DISEASES Many complexities at phenotype level. ‘Mendelian’ diseases
  • 14. Why this is needed Q: How many disease genes are there? A: Depends who and how you ask. OMIM: ‘genes phenotype-causing mutation’ = 3416 ‘phenotype description, molecular basis known’ = 4482 BioMart: Ensembl Genes: + Swiss Prot IDs and OMIM phenotype = 3268 Gene Cards: ‘disease genes’ = 9578
  • 15. TGMI Aims 1. To provide robust, comprehensive information on links between genes and human disease in a user- friendly interface. 2. To develop standardised frameworks for consistent clinical annotation and reporting of gene variation. 3. To develop approaches to deliver fast, automated, high-throughput, large-scale variant interpretation. 4. To develop and validate flexible, multipurpose analytical processes to maximise clinical and research utilities of genetic testing.
  • 16. TGMI – Aim 2 2.1 – Defining a Clinical Annotation Reference System (CARS) 2.2 – Defining a Clinical Sequencing Notation (CSN) 2.3 – Development and distribution of conversion tools
  • 17. Why this is needed • In the clinic and research settings there is huge variability in annotation of genetic variation at every level (gene name, transcript choice, variant annotation etc). • This inevitably compromises data integration, and clinical utility and fosters errors and harms.
  • 18. The CARS • The Clinical Annotation Reference System (CARS) encompasses the set of protein-coding genes, the set of reference transcripts and proteins corresponding to the genes, and a Clinical Sequencing Notation (CSN) for annotation of variation according to the sequences. • Defined against the reference human genome.
  • 19. TGMI gene set working criteria • Has an HGNC ID • Has an annotated start (which can be non- methionine) • Has an annotated stop • Occurs on chromosomes 1-22, X, Y, or MT • Has a gene and transcript biotype of “protein- coding” from Ensembl (release 84)
  • 20. The TGMI gene working set is comprised of 18,885 genes
  • 21. Clinical reference transcripts 1. Sequences must be based on the reference human genome. 2. The system must allow flexible iteration without compromising stability or clarity of sequence selection. 3. Reference transcripts must have durability, i.e. historical sequences used for clinical reporting that are subsequently superseded must remain available. 4. The reference transcript set should include as few sequences as possible (one per gene for most genes) but as many as required. 5. The reference transcript set must be easily available and usable to encourage universal uptake.
  • 22. CSN – Clinical Sequencing Notation • Once transcript is selected, the observed variant must be named according to its relative difference from the reference. • Fixed, standardised, automatic process for annotation of sequence variation • Consistent with historical HGVS guidelines
  • 23. TGMI Aims 1. To provide robust, comprehensive information on links between genes and human disease in a user- friendly interface. 2. To develop standardised frameworks for consistent clinical annotation and reporting of gene variation. 3. To develop approaches to deliver fast, automated, high-throughput, large-scale variant interpretation. 4. To develop and validate flexible, multipurpose analytical processes to maximise clinical and research utilities of genetic testing.
  • 24. Traditional interpretation process 1. Leveraging generic predictors, e.g. evolutionary conservation, protein structural features, impact on splicing etc to predict the functional consequences of individual variants (done in lab). 2. Leveraging expert assessment of clinical impact through disease and gene specific knowledge about the phenotype, genetic architecture, genotype- phenotype correlations, personal and family history and variant segregation etc (done in clinic).
  • 25. Interpretation requirements 1. High-throughput + large volume 2. Fast turnaround 3. Integrated into NGS pipelines 4. Integrated into clinical pipelines 5. Intelligible and usable by non-expert/patients
  • 27. Variant Phenotype Frequency of phenotype Mechanism of pathogenicity Inheritance pattern Attribution of gene for phenotype Penetrance of gene for phenotype Population variation Variability of gene Gene structure/function Much useful information can be utilised and automated so that the required manual curation can be focussed on the ~2-5% of variants where it is required.
  • 28. TGMI Aims 1. To provide robust, comprehensive information on links between genes and human disease in a user- friendly interface. 2. To develop standardised frameworks for consistent clinical annotation and reporting of gene variation. 3. To develop approaches to deliver fast, automated, high-throughput, large-scale variant interpretation. 4. To develop and validate flexible, multipurpose analytical processes to maximise clinical and research utilities of genetic testing.
  • 29. OpEx (Optimised Exome) pipeline https://github.com/RahmanTeam/OpEx www.icr.ac.uk/opex
  • 30. OpEx pipeline •Simple •To clinical standards •High-quality indel calling http://icr.ac.uk/opex https://github.com/RahmanTeam/OpEx • Comparisons with ExAC • Comparisons with clinical exome pipelines
  • 31. All input is welcome! • The TGMI is keen to hear from and engage with anyone interested in our aims. We are grateful for any input into what is needed in genetic medicine, how those needs are best met, and whether our solutions work. • How to stay in touch: – http://theTGMI.org – info@theTGMI.org – Weekly blog – Twitter: @theTGMI