I am not a PDBid I am a Biological Macromolecule

Philip E. Bourne

University of California San Diego

pbourne@ucsd.edu

Striving to be Recognized

• The “identity” of a macromolecular structure – functional and structural features and its broad role in a living system – is not established very easily by the majority of biologists. Given the technology available to us today surely it is time that this situation changed?

This is Not to Say that the Identity has not Improved

• Improved chemical description of polymers and monomers

• Remove sequence and taxonomic inconsistencies

• Improved representation of viruses

• Primary citation assignments

• REMARKS, SF files, NMR restraints….

Henrick et al. NAR 2008 36: D426-D433

For Example…• Chemical Components Dictionary:

– Model and idealized coordinates

– Chemical descriptors (e.g. SMILES) and systematic names

– Stereochemical assignments and aromatic bond assignments

– IUPAC nomenclature for standard amino acids and nucleotides with the exception of the well-established convention for C-terminal atoms OXT and HXT

– More conventional atom labeling

– Removal of redundant ligands

– Additional description of protonation states

This now sets the stage for the next stage of identity

development

The Problem Can be Defined as A Need to Change the Workflow

Workflow

Entry Point

Sequence

Literature

Structure

Function

Pathway…

The best way to change the workflow is to remove the barrier

between the literature (knowledge) and the PDB (data)

How Can This Happen?

Possibility 1 – ProteopediaA Completely New Beginning

• Advantages– Anyone can contribute simply – Community consensus seems to support

quality (e.g. Wikipedia)

• Disadvantages– Where is the reward?– Wiki format limited for providing a structural

identity

http://www.proteopedia.orgEran Hodis, Eric Martz, Jaime Prilusky, Joel L. Sussman

Possibility 2 - iSee

• Advantages– High quality annotation

• Disadvantages– Time consuming– Does not scale

http://www.sgc.ox.ac.uk/iSee

Possibility 3 – Database and Literature Integration

• Advantages– Reward through publication– Potentially comprehensive– Retains full power of the database and

literature

• Disadvantages– Literature accessibility– Harder to do

The Disadvantage of Literature Accessibility is Disappearing

Slowly

• The NIH Public Access Policy is a Term and Condition of Award for all grants and cooperative agreements active in Fiscal Year 2008 (October 1, 2007- September 30, 2008) or beyond, and for all contracts awarded after April 7, 2008.

So What is the Policy for NIH Sponsored Research?

• You can only agree to a journal copyright policy if that policy allows you to deposit the paper in PubMed Central (PMC)

• The paper must be deposited in PMC

• How this happens depends on the journal

BioLit http://biolit.ucsd.eduOur Effort at Database-Literature Integration

• J.L.Fink, S. Kushch, P. Williams & P.E.Bourne 2008 BioLit: Integrating Biological Literature with Databases NAR 36(S2) W385-389

• P.E.Bourne, J.L.Fink, M.Gerstein 2008 Open Access: Taking Full Advantage of the Content PLoS Comp. Biol. (Editorial) 4(3) e1000037

1. A link brings up figures from the paper

0. Full text of PLoS papers stored in a database

2. Clicking the paper figure retrievesdata from the PDB which is

analyzed

3. A composite view ofjournal and database

content results

BioLit: Tools for New Modes of Scientific Dissemination

• Biolit integrates biological literature and biological databases and includes:– A database of journal

text– Authoring tools to

facilitate database storage of journal text

– Tools to make static tables and figures interactive

4. The composite view haslinks to pertinent blocks

of literature text and back to the PDB

1.

2.

3.

4.

The Knowledge and Data Cycle

http://biolit.ucsd.edu

How Much of the Structure Literature is Currently Found in the Accessible PMC?

PMC Growth

0

2000

4000

6000

8000

10000

12000

14000

16000

1974

1976

1978

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

Year

Art

icle

s D

epo

site

d

• 74127 articles• 17161 were not

parasable• 7% - 3814 PDBids out

of 51633 referenced in ?? PMC articles

• 338 Figures have legends that include PDBids

ICTP Trieste, December 10, 2007

Where Can we Go From Here with BioLit?

The Ideal Situation is to Capture Relationships as the Paper is

Written

BioLit Plugin ProjectRather than Post-processing the Document the

Author Controls the Semantic Tagging

Author Paper

Word File in Docx formatPublisher

BioLit Plugin Project

Plugin Architecture

Context-Sensitive Data Access

• Display of information of database entries when the user clicks on the ID in the document

• Display of ontology terms related to terms in the document text, using local database search

Ontologies are Stored in a Local Database

User Configurable Selection

• Fully user configuration ontology and database identifier selection

• All searches occur within the user’s desktop computer

• Desired ontologies are downloaded and installed automatically, and update periodically

• BioLit installer XML file provides the application with the information needed to download and install ontologies.

Possibility 4. SciVee - A Different Kind of Learning Experience

Why not listen to the enthusiastic author talk about the structure

while you see the structure respond to their dialog?

YouTube for Scientists www.scivee.tv

Motivation

Pubcast – Video Integrated with the Full Text of the Paper

Pubcast - Making

PSP Washington DC Feb. 2008

Channels – Just Like TV

ICTP Trieste, December 2007

Professional Profile

ICTP Trieste, December 2007

Create & Join Communities and Discussion Groups

ICTP Trieste, December 2007

Finding What you Want

• Tag clouds generated automatically from MESH headings

• Full text of the papers indexed

• Browsing by audience type, subject, language etc.

SciVee – Viral Projects

• Sweetwater School District

• “Postercasts”

• Science video competitions

• “Pubumentaries”

Summary

• New modes of learning about structure are possible

• Number 6 never did get identified

• Time will tell whether a PDBid will become more than a number

Acknowledgements

• SciVee Team– Apryl Bailey– Tim Beck

– Leo Chalupa

– Marc Friedman– Alex Ramos– Willy Suwanto

• BioLit Team• J. Lynn Fink• Sergey Kushch• Parker Williams• Greg Quinn

CT Watch 2007, 3(3) 26-31

Questions?

pbourne@ucsd.edu

Questions?

pbourne@ucsd.edu