1. The ALS Online Database ALSoD
Ammar Al-Chalabi
ALSA Webinar
19 July 2011

2. ALS and genetics
There are many patterns of ALS

3. ALS and genetics There is a family history in about 5%
May be more if we all knew our family history

4. Family size affects family history
Smaller families provide fewer opportunities for someone to be affected
Less likely to have a family history
2 children
18% look sporadic
5 children
SOD1 mutations have about 70% penetrance
Al-Chalabi and Lewis, Human Heredity, 2011 in press

5. Family size affects family history
Smaller families provide fewer opportunities for someone to be affected
Less likely to have a family history
2 children
50% look sporadic
5 children
SOD1 mutations have about 70% penetrance
Al-Chalabi and Lewis, Human Heredity, 2011 in press

6. 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

7. What does this mean?
Although there is a genetic contribution to all ALS, it is not always a simple equation
gene mutation = ALS
Probably more like this:
ALS develops if the total risk passes this line
Gene 1
Gene 2
Lifestyle
Toxins
Virus

8. 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

9. 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

10. 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

11. 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

12. The new solution - ALSoD

13. 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

14. 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

15. 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

17. Walk through

21. Mutation information

22. Mutation information

23. Mutation information

24. Mutation information

25. Mutation information

26. Clinical information

31. Displaying genome-wide data

32. Displaying genome-wide data

33. Displaying genome-wide data

34. Displaying genome-wide data

35. Generating new information

36. Generating new information

37. Generating new information

40. Generating new information

41. Generating new information

45. Generating new information

46. Predicting interactions

48. Generating new information

51. Components in development

52. Mapping ALS risk

53. Developing a credibility score

54. Developing a credibility score
Still in beta
General ranking reasonable
Some surprising results

55. LOD score analysis Still in data collection phase
Cumulative evidence for new gene addresses

56. Working with ALSGene

57. ALSGene integration Direct links to ALSGene and vice versa
Will use RSS feeds to present results within ALSoD

58. Future developments

59. Apps
Android and iPhone app will allow easy access to ALSoD interface

60. Including FTD FTD website exists Initial contact made with curators
Hope to integrate data in similar way to ALSGene

61. Conclusions ALSoD allows easy up-to-date review of ALS genetics
New data and insights can be generated
Integration with other websites is key

62. 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