UMCCR Seminar Series

1. Community efforts in large scale genomics:
GA4GH and friends
Oliver Hofmann
University of Melbourne Centre for Cancer Research
1

2. Who we are
2
https://research.unimelb.edu.au/centre-for-cancer-research/home#research-new

3. Who we are
3
https://research.unimelb.edu.au/centre-for-cancer-research/home#research-new

4. What we do
HTS Platform Development
Technology Assessment
Community Engagement
4
Platform Development
Technology Assessment
Community engagement

5. What we do
HTS Platform Development
Technology Assessment
Community Engagement
5
Platform Development
Technology Assessment
Community engagement

6. WGS workflow
discussion
6
Somatic
SNV
Germline
SV
Somatic
CNV
Germline
CNV
Somatic
SV
Germline
SV
Pathogen
detection
Viral integration
Clonality
Mutational
signature
Ploidy
Purity
MSI sensing
HRD Detection
Genomic stability
Mutational burden
Telomere integrity
Clinical
prioritization
SV- gene
consequence
Drug-matching
Mutation
consequence
CNV-gene
consequence

7. 7
Vlad Saveliev Roman Valls
Lavinia GordonPeter Diakumis Sehrish Kanwal
Florian Reisinger
Team Melbourne
Brad Chapman
Rory Kirchner
Team Boston

8. CC BY 2.0, Marco Verch, https://www.flickr.com/photos/30478819@N08/43912339782
8

9. What we do
HTS Platform Development
Technology Assessment
Community Engagement
9
Platform Development
Technology Assessment
Community engagement

10. Rapid whole genome analysis
Supporting Precision Oncology
10

11. IT Infrastructure
Genomics Platform: Data flow
11
Data sharing
Curation &
Reporting
Primary
Processing
Post-
processing
Storing Data

12. Genomics Platform: Data flow
12
IT Infrastructure
Data sharing
Curation &
Reporting
Storing Data
Primary
Processing
Post-
processing

13. Genomics Platform: Processing
13
IT Infrastructure
Data sharing
Curation &
Reporting
Alignment
Trim Reads
Deduplication
Variant Calling
Ensemble Calls
QC
Callable region
detection
CNV Calls
SV Calls
Variant Filtering
Somatic
Signatures
Coverage
reports
…
Variant
Prioritisation
…
Primary
Processing
Post-
processing

14. Genomics Platform: Re-using methods
~120 software packages and counting
14
Alignment
Trim Reads
Deduplication
Variant Calling
Ensemble Calls
QC
Callable region
detection
CNV Calls
SV Calls
Variant Filtering
Somatic
Signatures
Coverage
reports
…
Variant
Prioritisation
…
Manta, BreakPointInspector
bwa-mem
sambamba
mosdepth
Strelka2, Vardict, Mutect2,
GATK Haplotype Caller
MultiQC
atropos
Purple
bcftools
MutationalPatterns
svprioritise, PCGR, CPSR
Cocoa, indexcov

15. How to pick: Suitable
Kim et al (2018): Experimenting with reproducibility:
a case study of robustness in bioinformatics
15

16. How to pick: Validation
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Caller:
Dragen
Ensemble
Strelka2
VariantCount
Allelic Frequency

17. How to pick: Maintenance
https://github.com/bcbio/
17

18. How to pick: Support
https://github.com/sigven/pcgr/
18
Sigve Nakken

19. 19
Contributing back

20. https://zenodo.org/record/3351537
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21. Mateusz Kuzak: Software Development Best Practices
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22. Mateusz Kuzak: Software Development Best Practices
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23. Mateusz Kuzak: Software Development Best Practices
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24. Mateusz Kuzak: Software Development Best Practices
24

25. 25
“A piece of software is being sustained
if people are using it, fixing it, and
improving it rather than replacing it.”
software-carpentry.org/blog/2014/08/sustainability.html
Maintain code

26. 26
https://github.com/bcbio/bcbio_validation_workflows
Share (validation) data

27. https://umccr.org/blog/
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Make it findable, stand out
Publish blog posts

28. https://zenodo.org/record/3351537
28

29. https://zenodo.org/record/3351537
29

30. 30
From Tools to Standards
Interoperability

31. https://www.ga4gh.org/
31

32. <context>
32

33. 33
Direct Engagement
Indirect Engagement

34. 34

35. </context>
35

36. IT Infrastructure
Genomics Platform: Data flow
36
Data sharing
Curation &
Reporting
Primary
Processing
Post-
processing
Genomic
Repository

37. Data sharing
Curation &
Reporting
Genomic
Repository
Primary
Processing
Post-
processing
Genomics Platform: Data flow
37
IT Infrastructure

38. Moving code to the data
https://www.ga4gh.org/work_stream/cloud/
38

39. 39
Sharing tools
and workflows
Executing
workflows
Executing tasks
Accessing Data

40. https://github.com/ga4gh/workflow-execution-service-schemas
40
Processing: Workflow execution service (WES)

41. Common
Workflow
Language
Because we will never agree on one
execution system
41

42. Common
Workflow
Language
Because we will never agree on one
execution system
… or workflow language
42

43. (Towards) Interoperability
43
Mini-WDL (Mike Lin)
https://github.com/chanzuckerberg/miniwdl
Janis (Richard Lupat)
https://github.com/PMCC-BioinformaticsCore/janis
CWL-Ex (Peter Amstutz)
https://github.com/common-workflow-language/cwl-ex

44. Access: Data Repository Schema (DRS)
https://github.com/ga4gh/data-repository-service-schemas
44

45. GA4GH 2019 Roadmap
45

46. 46

47. https://www.australiangenomics.org.au/
47

48. 48

49. Clinical consultation
Genome Data
Store
Clinical Sequencing
Laboratory
Quality Assessment
qProfiler
FLAGSHIPS
Curated Variant Store
Australian Genomics Data Flow
SNOMED-CT
BAM
VCF
Reported annotated
variants
Unreported annotated
variants
Patient Archive
Hospital EMR
Clinician +
Clinical notes
(e.g. family history, clinical
features)
Pathology test results
Biographical data
Biospecimen
Consent
Matchmaker Exchange
HPO
FASTQ
Variant Atlas
Hospital EMR
Patient Archive
PROGRAM 2
1. Phen-gen queries
2. Allele frequency queries
3. Variant browsing
4. Cohort visualisation
5. Cohort statistics
6. Sharing and collaboration
7. Variant Beacon
1. Big data storage / archiving
2. Data sharing
1. Data quality assessment
1. Variant classification
harmonisation
2. Curated variant sharing
3. Curated variant matching
1. Patient-level clinical data store
2. Phenotype analytics
3. Granulised patient-level clinical
data sharing
4. Local patient matching
PURPOSE / CAPABILITY
1. International patient matching
CML
Pipeline Registry
1. Pipeline description
2. Pipeline comparison
FHIRCap
Phenotype Database
(FHIR)
1. Complex phenotype queries
AGHA Data Flow
49

50. Clinical consultation
Genome Data
Store
Clinical Sequencing
Laboratory
Quality Assessment
qProfiler
FLAGSHIPS
Curated Variant Store
SNOMED-CT
BAM
VCF
Reported annotated
variants
Unreported annotated
variants
Patient Archive
Hospital EMR
Clinician +
Clinical notes
(e.g. family history, clinical
features)
Pathology test results
Biographical data
Biospecimen
Consent
Matchmaker Exchange
HPO
FASTQ
Variant Atlas
Hospital EMR
Patient Archive
PROGRAM 2
1. Phen-gen queries
2. Allele frequency queries
3. Variant browsing
4. Cohort visualisation
5. Cohort statistics
6. Sharing and collaboration
7. Variant Beacon
1. Big data storage / archiving
2. Data sharing
1. Data quality assessment
1. Variant classification
harmonisation
2. Curated variant sharing
3. Curated variant matching
1. Patient-level clinical data store
2. Phenotype analytics
3. Granulised patient-level clinical
data sharing
4. Local patient matching
PURPOSE / CAPABILITY
1. International patient matching
CML
Pipeline Registry
1. Pipeline description
2. Pipeline comparison
FHIRCap
Phenotype Database
(FHIR)
1. Complex phenotype queries
AGHA Data Flow
50
Clinical data capture
Consent &
Data Use
Storing data Data sharing

51. Storage: CRAM
http://ga4gh.org/cram
51

52. Storage: Crypt4GH
Encrypted container formats: https://github.com/uio-bmi/crypt4gh
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53. Dissemination: htsget
http://samtools.github.io/hts-specs/htsget.html
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54. Dissemination: Local EGA
https://localega.readthedocs.io
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55. Access: Data Use & Researcher Identities
Simplifying data access requests
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56. Access: Data Use & Researcher Identities
Simplifying data access requests
56

57. Automating discovery & access for controlled access data
https://github.com/EBISPOT/DUO
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Data Use Ontology (DUO)

58. Regulatory & Ethics: Dynamic consent
https://demo-ctrl.australiangenomics.org.au/
58

59. Discovery: Beacon
https://beacon-network.org/
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60. Discovery: Matchmaker
Australian Genomics Health Alliance Patient Archive
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61. Discovery: Standardise Data in REDCap
REDCap Plugin: Collecting standard terminologies via an external FHIR server, https://github.com/aehrc/redcap_fhir_ontology_provider
Ontoserver, https://genomics.ontoserver.csiro.au/
61

62. Discovery: REDCap to FHIR
Converting data captured in REDCap to FHIR Resources & http://phenopackets.org/
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63. Discovery: Search API
https://github.com/ga4gh-discovery/ga4gh-discovery-search
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64. Discovery: Search API
https://github.com/ga4gh-discovery/ga4gh-discovery-search
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65. Discovery: Search API
https://www.ga4gh.org/work_stream/discovery/
65

66. Discovery: Search API
https://www.ga4gh.org/work_stream/discovery/
66

67. DNAStack Pilot
67
GA4GH interoperability testbed

68. Do we need this automation?
National Medical Genome Projects & Cohorts as gathered by EMBL-EBI/GAGH (2019)
68

69. 69
Genomics in healthcare (doi.org/10.1101/203554)

70. 70
https://www.ga4gh.org/how-we-work/workstreams/
https://www.ga4gh.org/event/ga4gh-6th-plenary/
Look at meeting minutes
Join calls
Work with GA4GH

71. Work with us
https://github.com/umccr
oliver.hofmann@unimelb.edu.au
@fiamh
71
Vlad Saveliev Roman Valls
Lavinia GordonPeter Diakumis Sehrish Kanwal
Florian Reisinger
?
We are hiring

72. The Victorian Cancer Bioinformatics Symposium
Registrations and abstracts now open!
Abstract deadline is 22 June.
http://viccancerbioinfsymposium.org/
Friday 16th August 2019 at the Victorian Comprehensive Cancer Centre
Prof Shannon McWeeney
Oregon Health Sciences University
Portland, USA
Prof Vanessa Hayes
Garvan Institute
Sydney, Australia
A.Prof Mark Cowley
Children’s Cancer Institute of Australia
Sydney, Australia
Prof Christin Print
University of Auckland
Auckland, New Zealand
http://viccancerbioinfsymposium.org/
72

73. 73

74. https://github.com/umccr
oliver.hofmann@unimelb.edu.au
@fiamh
74