Open Notebook Science for Collaborative Drug Discovery Jean-Claude Bradley July 23, 2009 BrightTALK Associate Professor of Chemistry Drexel University

WE ARE HERE How can the scientific process become more automated?

The Robot Scientist

Agents can participate with zero or near-zero cost (free hosted services – e.g. Google) Self-organizing redundant processes How radical openness can assist in the automation of science

Agents can participate with zero or near-zero cost (free hosted services – e.g. Google)

Self-organizing redundant processes

UsefulChem Project: Open Primary Research in Drug Design using Web2.0 tools Docking Synthesis Testing Rajarshi Guha Indiana U JC Bradley Drexel U Phil Rosenthal UCSF (malaria) Dan Zaharevitz NCI (tumors) Tsu-Soo Tan Nanyang Inst.

Malaria Target: falcipain-2 involved in hemoglobin metabolism Dana.org

Outcome of Guha-Bradley-Rosenthal collboration

The Ugi reaction: can we predict precipitation? Can we predict solubility in organic solvents?

Open and Closed Science Traditional Lab Notebook (unpublished) Traditional Journal Article Open Access Journal Article Open Notebook Science (full transparency) CLOSED OPEN Traditional Paper Textbook F2F lectures Lectures Notes public Assigned problems public Archived Lectures Public and free online textbooks RESEARCH TEACHING

Motivation: Faster Science, Better Science

Open Notebook Science Logos (Andy Lang, Shirley Wu) Sharing: how much and when

There are NO FACTS, only measurements embedded within assumptions Open Notebook Science maintains the integrity of data provenance by making assumptions explicit

TRUST PROOF

The solubility of 4-chlorobenzaldehyde

The Log makes Assumptions Explicit

Results and Workflows in Machine-Friendly Format

The Rationale of Findings Explicit

Raw Data Made Public Splatter? Some liquid

YouTube for demonstrating experimental set-up

Calculations Made Public on Google Spreadsheets

Link to Docking Results: Lists of SMILES in GoogleDocs (Rajarshi Guha)

Link to Docking Procedure (Rajarshi Guha)

Revision History on Google Spreadsheets

Wiki Page History

Comparing Wiki Page Versions

Proof of Purity with interactive NMR spectrum using JSpecView and JCAMP-DX

Linking to Molecules in Chemistry Databases

Experimental Spectra and User-Deposited Data on ChemSpider

(Andy Lang, Tony Williams) Open Data JCAMP spectra for education (Andy Lang, Tony Williams, Robert Lancashire)

Database Curation via Game Playing

Over 50,000 spectrum views so far - worldwide

Link Spectral Game to Open Educational Content

NMR game in Second Life (Andy Lang)

Crowdsourcing Solubility Data

ONS Challenge Students

ONS Challenge Judges

Semi-Automated Measurement of solubility via web service analysis of JCAMP-DX files (Andy Lang)

Teaching Lab: Brent Friesen (Dominican University)

Solubility Experiment List

Solubilities collected in a Google Spreadsheet

Rajarshi Guha’s Live Web Query using Google Viz API

Rajarshi Guha and Andy Lang: Chemical Space Explorer

Solubility Measurement Requests: DoSol sheet Outlier Bot: flags measurements with high standard deviation to mean ratios Google Analytics queries – new solvent/solute searches Solubility request form – researcher in Israel requesting pyrene in acetonitrile solubility for environmental soil contamination study Application based models – high priority Ugi reactants

Outlier Bot: flags measurements with high standard deviation to mean ratios

Google Analytics queries – new solvent/solute searches

Solubility request form – researcher in Israel requesting pyrene in acetonitrile solubility for environmental soil contamination study

Application based models – high priority Ugi reactants

Solvent mixture and temperature: multidimensional solubility data Actual Data (4-nitrobenzaldehyde) From quadratic regression of 5D space Feeds DoSol Sheet the next points to measure to best cover the space

Comparing Experiments Ugi Master Table

Crowdsourcing Reaction Requests: DoUgi sheet

Raw data reveal a problem Missed in a prior publication on solubility for this compound

Data provenance: From Wikipedia to…

… the lab notebook and raw data

Including links to the literature

Collaborative Drug Discovery (CDD) Database

Concentration (0.4, 0.2, 0.07 M) Solvent (methanol, ethanol, acetonitrile, THF) Excess of some reagents (1.2 eq.) How does Open Notebook Science fit with traditional publication?

Concentration (0.4, 0.2, 0.07 M)

Solvent (methanol, ethanol, acetonitrile, THF)

Excess of some reagents (1.2 eq.)

Mettler-Toledo MiniMapper

Mettler-Toledo MiniBlock System

XML reports from MiniMapper robot

GoogleDoc to program and report

Best Yield: 66% 0.4 M methanol 1.2 eq imine

Reaction Optimization Visualization in Second Life

Paper written on Wiki

References to papers, blog posts, lab notebook pages, raw data

Paper on Journal of Visualized Experiments (JoVE)

Pre-print on Nature Precedings

ChemSpider Automated Mark-up of Chemical Names

Archiving and Curation of ONS and other new forms of scholarship?

Cameron Neylon’s Notebooks Other Open Notebooks

Anthony Salvagno’s Notebook (Steve Koch group)

Acknowledgements Khalid Mirza (Drexel) Jenny Hale (Southampton U.) David Bulger (Oral Roberts U.) Tim Bohinsky (Drexel) Kevin Owens (Drexel) Tom Osborne (Mettler-Toledo) Antony Williams (ChemSpider) Andrew Lang (Oral Roberts U.) Rajarshi Guha (Indiana U.) Cameron Neylon (Southampton U.)

Khalid Mirza (Drexel)

Jenny Hale (Southampton U.)

David Bulger (Oral Roberts U.)

Tim Bohinsky (Drexel)

Kevin Owens (Drexel)

Tom Osborne (Mettler-Toledo)

Antony Williams (ChemSpider)

Andrew Lang (Oral Roberts U.)

Rajarshi Guha (Indiana U.)

Cameron Neylon (Southampton U.)