Transcript The ALS Online Database ALSoD

The ALS Online Database
ALSoD
Ammar Al-Chalabi
ALSA Webinar
19 July 2011
ALS and genetics
• There are many
patterns of ALS
ALS and genetics
• There is a family
history in about 5%
– May be more if we all
knew our family history
Family size affects family history
– Less likely to have
a family history
0.9
Proportion sporadic
• Smaller families
provide fewer
opportunities for
someone to be
affected
1
0.8
2 children
0.7
0.6
0.5
0.4
0.3
18% look sporadic
0.2
5 children
0.1
0
0
0.2
0.4
0.6
0.8
1
Penetrance
SOD1 mutations have about 70%
penetrance
Al-Chalabi and Lewis, Human Heredity, 2011 in press
Family size affects family history
– Less likely to have
a family history
0.9
Proportion sporadic
• Smaller families
provide fewer
opportunities for
someone to be
affected
1
0.8
2 children
0.7
0.6
0.5
50% look sporadic
0.4
0.3
0.2
5 children
0.1
0
0
0.2
0.4
0.6
0.8
1
Penetrance
SOD1 mutations have about 70%
penetrance
Al-Chalabi and Lewis, Human Heredity, 2011 in press
ALS and genetics
• Twin studies show a genetic contribution to
apparently sporadic ALS
– Siblings have about 8-fold increased risk of ALS
– Still very unlikely to get ALS
General population
99.7% chance of not
having ALS
Siblings of an
affected person
97.6% chance of
not having ALS
Al-Chalabi, JNNP 2010, Hanby MF, 2011, Brain in press
What does this mean?
• Although there is a genetic contribution to
all ALS, it is not always a simple equation
gene mutation = ALS
ALS develops if the total
risk passes this line
• Probably more like this:
Gene 1
Gene 2
Lifestyle
Toxins
Virus
What does this mean?
• Finding the genes
that increase ALS risk
is not easy
– Probably a few big
effect genes and
hundreds of small
effect genes
Which genes cause ALS?
• 96 genes so far
implicated in ALS
– Some have better evidence
than others
– Most researchers accept
SOD1, TDP43, and FUS as
ALS genes
– Many accept OPTN, VCP,
VAPB, ANG, ATXN2
– Some accept NEFH, ELP3
How can we keep up?
• Keeping up with ALS
genetics is
challenging
• Reviewing the
credibility of each
gene is challenging
• Seeing patterns in the
data is challenging
The old solution (reviews)
• Review articles
– One person’s view of
the state of play
• Summarize all the
literature
– But need to wait for
one to come along
– May not answer what
you need
– May be biased
The new solution - ALSoD
Displaying existing knowledge
• The ALS Online
Database (ALSoD)
– Aims to summarize
everything known
about ALS genetics in
one place
• Useful for researchers
• Patterns in the data
can be searched for
Displaying existing knowledge
• The ALS Online
Database (ALSoD)
– Aims to summarize
everything known
about ALS genetics in
one place
• Useful for researchers
• Patterns in the data
can be searched for
Displaying existing knowledge
• The ALS Online
Database (ALSoD)
– Aims to summarize
everything known
about ALS genetics in
one place
• Useful for researchers
• Patterns in the data
can be searched for
Walk through
Mutation information
Mutation information
Mutation information
Mutation information
Mutation information
Clinical information
Displaying genome-wide data
Displaying genome-wide data
Displaying genome-wide data
Displaying genome-wide data
Generating new information
Generating new information
Generating new information
Generating new information
Generating new information
Generating new information
Predicting interactions
Generating new information
Components in development
Mapping ALS risk
Developing a credibility score
Developing a credibility score
• Still in beta
• General ranking reasonable
• Some surprising results
LOD score analysis
• Still in data collection
phase
• Cumulative evidence
for new gene
addresses
Working with ALSGene
ALSGene integration
• Direct links to
ALSGene and vice
versa
– Will use RSS feeds to
present results within
ALSoD
Future developments
Apps
• Android and iPhone
app will allow easy
access to ALSoD
interface
Including FTD
• FTD website exists
– Initial contact made
with curators
– Hope to integrate data
in similar way to
ALSGene
Conclusions
• ALSoD allows easy
up-to-date review of
ALS genetics
• New data and insights
can be generated
• Integration with other
websites is key
Acknowledgements
• Bunmi Abel is the computer
scientist who has written the
bulk of ALSoD
– Previous website designers
• Richard Wroe
• Ian Gowrie
• Original idea for ALSoD from
Aleks Radunovic and Nigel
Leigh
• Funding
– Generous long-term funding
from ALSA and MNDA
– Additional funding from MNDA
Iceland, ALS Society of
Canada, ALS Therapy Alliance
• Adopted by World Federation
of Neurology and European
Network for the Cure of ALS