1. InterPro An Introduction
2nd IMPACT workshop
5-6 May, 2010
InterPro An Introduction
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

2. European Bioinformatics Institute Wellcome Trust Genome Campus
Overview
What InterPro is
Where it came from
What the vision was
Has it evolved in line with that vision?
Is it still fit for purpose?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

3. European Bioinformatics Institute Wellcome Trust Genome Campus
What is InterPro?
According to the User Manual: “InterPro is an integrated documentation resource for protein families, domains & sites. InterPro combines a number of databases that use different methodologies & a varying degree of biological information on well-characterised proteins to derive protein signatures. By uniting the member databases, InterPro capitalises on their individual strengths, producing a powerful integrated database & diagnostic tool.”
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

4. European Bioinformatics Institute Wellcome Trust Genome Campus
Where did it come from?
The concept of an integrated protein family database emerged almost 20 years ago!
at the 1991 BCA spring meeting in Sheffield
Amos Bairoch had a poster on PROSITE
I had one on a ‘fingerprint’ database…
We recognised that our approaches were under-pinned by similar philosophies
to provide meaningful biological information
to provide high quality manual annotation
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

5. European Bioinformatics Institute Wellcome Trust Genome Campus
Where did it come from?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

6. European Bioinformatics Institute Wellcome Trust Genome Campus
Where did it come from?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

7. European Bioinformatics Institute Wellcome Trust Genome Campus
Where did it come from?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

8. Where did it come from? PROSITE & PRINTS were different
but somehow also the same…
most importantly, they were complementary
In combination, we gain powerful structural & functional insights
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

9. European Bioinformatics Institute Wellcome Trust Genome Campus
Where did it come from?
So where next?
we had created 30 family fingerprints
PROSITE documented 375 families & functional sites
PROSITE was way ahead!
we were still on the starting blocks…
Nevertheless, we decided to apply for an EU grant to unite the databases
…seemed like a good idea at the time!
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

10. European Bioinformatics Institute Wellcome Trust Genome Campus
What was the vision?
Naïvely, we wanted to make life easier!
We aimed to
simplify & rationalise protein family analysis
ensuring that entries & their linked signatures pointed to related information on the same biological object
centralise & streamline the annotation process
reduce manual annotation burdens
facilitate automatic functional annotation of uncharacterised proteins
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

11. European Bioinformatics Institute Wellcome Trust Genome Campus
How has it evolved?
The EU proposal was submitted in 1992
and was promptly declined!
Later, in 1995, the EBI was established at Hinxton
Visiting Fellowship in 1997
to help integrate my work more closely with that of EBI
Rolf, Amos & I decided to try again for an EU grant
by then, Profiles, ProDom & Pfam had also been created
so it made sense to include them too
With the bigger picture, the grant succeeded
- InterPro was born!
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

12. European Bioinformatics Institute Wellcome Trust Genome Campus
How has it evolved?
Prosite
Release 0.1 beta was made in October 1999
It contained 2,423 entries
1,370 PROSITE entries
1,465 Pfam entries
1,157 PRINTS entries
241 preliminary profiles
Based on Swiss-Prot 38 & TrEMBL 11
ProDom
ProDom
PRINTS
InterPro
Profiles
Pfam
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

13. European Bioinformatics Institute Wellcome Trust Genome Campus
How has it evolved?
“Various factors rendered a step-wise approach to the development of InterPro desirable. First, the scale of the task of amalgamating just the first 3 databases was immense. The rational merging of apparently equivalent database entries that in fact simultaneously define a specific family, domains within that family, or even repeats within those domains, presented an enormous challenge.”
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

14. European Bioinformatics Institute Wellcome Trust Genome Campus
How has it evolved?
domain family
super-family
families
sub-families
Unravelling the biological relationships is vital!
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

15. European Bioinformatics Institute Wellcome Trust Genome Campus
How has it evolved?
Clearly, the task of integration was hard
understanding the biological relationships being represented within member databases, let alone between them, was proving to be a significant challenge
Rather than making our lives easier, it was probably making them much harder!
…& that was just with 3 databases!
Today, with 11 sources, life is harder still…
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

16. European Bioinformatics Institute Wellcome Trust Genome Campus
How has it evolved?
Release 26.0, March 2010
It contains 20,329 entries
1,023 Gene3D entries
620 HAMAP entries
2,234 Panther entries
2,744 PIRSF entries
1,975 PRINTS entries
1,291 PROSITE regexs
836 PROSITE profiles
11,056 Pfam entries
803 SMART entries
1,095 SUPERFAMILY entries
3,689 TIGRFams
Release 0.1 beta was made in October 1999
It contained 2,423 entries
1,370 PROSITE entries
1,465 Pfam entries
1,157 PRINTS entries
241 preliminary profiles
Based on Swiss-Prot 38 & TrEMBL 11
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

17. Is InterPro still fit for purpose?
The database has grown almost 10-fold in ~11 years
Why was it created in the first place?
to simplify & rationalise protein family analysis
ensuring that entries & their linked signatures pointed to related information on the same biological object
to centralise & streamline the annotation process
& reduce manual annotation burdens
to facilitate automatic functional annotation of uncharacterised proteins
to make life easier!!
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

18. Is InterPro still fit for purpose?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

19. Is InterPro still fit for purpose?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019 19

20. Is InterPro still fit for purpose?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

21. Is InterPro still fit for purpose?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

22. Is InterPro still fit for purpose?
Why separate out structurally & functionally relevant information?
Remember this?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

23. European Bioinformatics Institute Wellcome Trust Genome Campus
What is InterPro?
A reminder: “InterPro is an integrated documentation resource for protein families, domains & sites. InterPro combines a number of databases that use different methodologies & a varying degree of biological information on well-characterised proteins to derive protein signatures. By uniting the member databases, InterPro capitalises on their individual strengths, producing a powerful integrated database & diagnostic tool.”
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

24. Is InterPro still fit for purpose?
Integration = greater than the sum of the parts
- a perfect example…
This integrated view is incredibly powerful & informative!
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

25. Is InterPro still fit for purpose?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

26. Is InterPro still fit for purpose?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

27. Is InterPro still fit for purpose?
What does it mean?
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

28. Is InterPro still fit for purpose?
They’re still not the same!
Let’s see what the alignments actually look like
- consider just the first 3 TM domains…
They’re not the same!
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

29. Is InterPro still fit for purpose?
In the process of growing bigger, InterPro has grown massively in complexity
Its internal convolutions now challenge us to ask, “What does it mean?”
what does it all mean to end users?!
& what does it all mean to computers?!
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

30. Has it evolved in line with its vision?
With IMPACT, yes, InterPro has an opportunity to realise its original vision
it can rationalise protein family analysis
it can help to streamline the annotation process
it can facilitate functional annotation of proteins
it can make life easier
but it can only do these things if we’re prepared to empathise, collectively, with its growing pains!
That’s why this workshop is important
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

31. Is InterPro still fit for purpose?
“There is a tremendous amount of information regarding evolutionary history and biochemical function implicit in each sequence and the number of known sequences is growing explosively. We feel it is important to collect this significant information, correlate it into a unified whole and interpret it.”
Margaret O. Dayhoff to C.Berkley, February 27th, 1967
That is still InterPro’s unique opportunity!
“To kill an error is as good a service as, and sometimes even better than, the establishing of a new truth or fact.”
Charles Darwin, 1879
This remains IMPACT’s imperative!
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

32. European Bioinformatics Institute Wellcome Trust Genome Campus
A workshop
5-6 May, 2010
Day 1
Registration Domestic InterPro, an introduction (Terri) Single-motif signatures: pros, cons & added-value to InterPro (Nicolas) Multiple-motif signatures: pros, cons & added-value to InterPro (Alex) Coffee Domain-based signatures: pros, cons & added-value to InterPro (Rob) Structural annotation: pros, cons & added-value to InterPro (Corin) InterPro today [including GO mapping] (Sarah) Lunch How InterPro is used to add functional annotation to UniProt (Claire) Hands-on examples Coffee Open discussion/feedback Dinner
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019

33. European Bioinformatics Institute Wellcome Trust Genome Campus
A workshop
5-6 May, 2010
Day 2
Issues with integrating different signatures: domains Issues with integrating different signatures: families and subfamilies Meaningful terms to group signatures and name entries Coffee 11:30-12:00 Unexpected sequences in match lists & how to reconcile them Improving InterPro’s interface to better visualise, integrate & maintain data Open discussions Lunch ??? Format/outline/organisation of November outreach event Future funding Reviewer feedback Review of EoY deliverables – status report & action plan AOB
European Bioinformatics Institute Wellcome Trust Genome Campus
2/24/2019