Sample to Insight
Hands-on Workshop
Clinical Genomics - Interpretation and Reporting with QIAGEN Bioinformatics
Ruth Burton PhD. – Clinical Applications Specialist ([email protected])
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 1
Sample to Insight
Clinical Genomics - Interpretation and Reporting with QIAGEN Bioinformatics
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 2
Agenda
• Introduction to the portfolio
• Getting started with IVA
• Filtering a whole exome sample
• Somatic analysis in QCI I
• Working with a trio
• Hereditary analysis in QCI I
• Uploading and sharing samples
• Working with your own data
Sample to Insight
Clinical Genomics - Interpretation and Reporting with QIAGEN Bioinformatics
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 3
Introduction to the portfolio
Sample to Insight
Clinical Genomics - Interpretation and Reporting with QIAGEN Bioinformatics
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 4
Introduction to the portfolio
Sample to Insight
Clinical Genomics - Interpretation and Reporting with QIAGEN Bioinformatics
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 5
Introduction to the portfolio
Sample to Insight
Clinical Genomics - Interpretation and Reporting with QIAGEN Bioinformatics
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 6
Getting started with IVA
Log-on
https://www.qiagenbioinformatics.com/product-login/
See your sheet for number!
Login name:
Password: variant123
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 7
Logging on
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 8
Logging on
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 9
Welcome screen
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 10
Welcome screen, may see other info such as T&Cs or a sample is waiting to be imported…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 11
Find the demo sample, the default view is analysis – we need to find the sample
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 12
Change to samples and search for “WEX”
Highlight sample and click “Analyze”
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 13
A series of options follows, guiding you through the analysis
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 14
A series of options follows, guiding you through the analysis
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 15
A series of options follows, guiding you through the analysis
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 16
A series of options follows, guiding you through the analysis
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 17
A series of options follows, guiding you through the analysis
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 18
A series of options follows, guiding you through the analysis
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 19
Can wait for the email or press “Refresh”
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 20
When active can open analysis and review the filtering steps
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 21
When active can open analysis and review the filtering steps
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 22
A filtering cascade has been applied… let’s look at the filters in order
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 23
A filtering cascade has been applied… let’s look at the filters in order
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 24
A filtering cascade has been applied… let’s look at the filters in order
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 25
A filtering cascade has been applied… let’s look at the filters in order
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 26
A filtering cascade has been applied… let’s look at the filters in order
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 27
A filtering cascade has been applied… let’s look at the filters in order
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 28
A filtering cascade has been applied… let’s look at the filters in order
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 29
As well as filtering IVA provides a wealth of information…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 30
As well as filtering IVA provides a wealth of information…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 31
As well as filtering IVA provides a wealth of information…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 32
As well as filtering IVA provides a wealth of information…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 33
As well as filtering IVA provides a wealth of information…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 34
What can you do with your filtered list?
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 35
To export to QCI I you need a QCI I account
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 36
To export to QCI I you need a QCI I account
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 37
Choose your workflow
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 38
Add in patient meta data
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 39
Add in patient meta data
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 40
The software will “learn” from your classifications…
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 41
Further meta data…
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 42
Further meta data…
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 43
Option for customized report…
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 44
Go to results…
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 45
The list of variants…
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 46
Two views… a lot of information is already given about the variant
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 47
ACMG Guidelines are used for classification
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 48
Variant details provide supporting evidence for classification
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 49
Variant details provide supporting evidence for classification
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 50
Variant details provide supporting evidence for classification
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 51
Key step is creating a report
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 52
Key step is creating a report
Sample to Insight
QCI I Demo
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 53
Key step is creating a report
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 54
Trio Analysis, highlight and click “Open”
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 55
Here we have a different set up and filters, click on the top of the filter cascade…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 56
While the same principles are used as with the single sample here we can use the parental samples to detect de novo variants in the child…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 57
After the genetic analysis filter only variants unique to the proband remain
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 58
Refine this further using phenotype information…
Sample to Insight
Phenotype-driven Ranking Algorithm
• Enter a phenotype (free text or HPO)
• KB returns matches – 44,000 variants current associated with phenotypes
• Evidence from KB connects variants with phenotypes/ disease
• The relevance of the connection “graded” by a score
• Consideration given to overall occurrence of the phenotype in the KB
• Allows the score to be adjusted for specificity and confidence improving accuracy
Mapping of phenotypes to variants
Sample to Insight
Scoring algorithm
Nd = number of diseases connected to the phenotype (the more diseases the lower the specificity)
N = number of links between phenotype and variant (the greater the number of links the lower the confidence)
High scores achieved for variants with few diseases connecting directly to a phenotype
Specificity
Confidence
Score
Sample to Insight
IVA
Disease-gene pair ranked by the score generated using phenotype-disease relationship
Sample to Insight
IVA
Each connection displayed as a network showing Gene-Disease-Phenotype relationship
Variant containing gene
Disease / syndrome
Phenotypes
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 63
The result is a list of variants prioritized by the relationship with the patients phenotype
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 64
Can view the key genes and variants…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 65
Loading your own data…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 66
There are two options for large files the datastream is better…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 67
Just drag and drop your files…
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 68
Sharing samples, ideal if you want to create your own account
Sample to Insight
IVA Workshop
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 69
Sharing samples, ideal if you want to create your own account
Sample to Insight
Clinical Genomics - Interpretation and Reporting with QIAGEN Bioinformatics
QIAGEN Sample to Insight | www.qiagenbioinformatics.com | www.qiagen.com 70
Any questions?
Come and visit us at our stand
www.qiagenbioinformatics.com