Accelerating Discovery by Sharing: a case for Open

Notebook Science

Jean-Claude Bradley

May 1, 2011

National Breast Cancer Coalition Annual Advocacy Conference

Associate Professor of ChemistryDrexel University

Outline

1. Trends in sharing for drug discovery

2. ONS for malaria research3. Crowdsourcing solubility with

ONS4. Leveraging the educational

system to contribute new science

5. Open modeling and web services

6. Discovering connections7. Moving forward: tools and

practices

Industry is Sharing More

Opportunities for Competitive Collaboration

Some Initiatives Promoting More Openness in Drug Discovery

Motivation: Faster Science, Better Science

There are NO FACTS, only measurements embedded

within assumptions

Open Notebook Science maintains the integrity of data

provenance by making assumptions explicit

TRUST

PROOF

First record then abstract structure

In order to be discoverable use Google friendly formats (simple HTML, no

login) In order to be replicable use free hosted tools (Wikispaces, Google

Spreadsheets)

Strategy for an Open Notebook:

UsefulChem Project:UsefulChem Project: Open Primary Open Primary Research in Drug Design using Web2.0 Research in Drug Design using Web2.0

toolstools

Docking

Synthesis

Testing

Rajarshi GuhaIndiana U

JC BradleyDrexel U

Phil RosenthalUCSF

(malaria)

Dan ZaharevitzNCI

(tumors)

Tsu-Soo TanNanyang Inst.

Malaria Target: falcipain-2 involved in hemoglobin metabolism

Dana.org

The Ugi Reaction

Outcome of Guha-Bradley-Outcome of Guha-Bradley-Rosenthal collaborationRosenthal collaboration

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

data

The Ugi reaction: can we predict precipitation?

Can we predict solubility in organic solvents?

Crowdsourcing Solubility Data

ONS Challenge Judges

ONS Challenge Award Winners

Solubilities collected in a Google Spreadsheet

Rajarshi Guha’s Live Web Query using Google Viz API

Data provenance: From Wikipedia to…

…the lab notebook and raw data

Interactive NMR spectra using JSpecView and JCAMP-DX

(Andy Lang, Tony Williams)

Open Data JCAMP spectra for education

(Andy Lang, Tony Williams, Robert Lancashire)

Raw Data As Images

Splatter?

Some liquid

YouTube for demonstrating experimental YouTube for demonstrating experimental set-upset-up

The importance of raw data availability

Missed in a prior publication on

solubility for this compound

Case study: Chemical Information

Retrieval course at Drexel (Fall 2009/2010)

Leveraging the educational system to contribute new science

The Chemical Information Validation Sheet

567 curated and referenced measurements from Fall 2010 Chemical Information Retrieval course

The Chemical Information Validation Explorer

(Andrew Lang)

Discovering outliers for melting points (stdev/average)

Investigating the m.p. inconsistencies of EGCG

Investigating the m.p. inconsistencies of cyclohexanone

Sigma-Aldrich, Acros and Wolfram Alpha apparently use the same sources for melting

points

Sigma-Aldrich, Acros and Wolfram Alpha apparently use the same sources for boiling

points

Sigma-Aldrich, Acros and Wolfram Alpha apparently

DO NOT use the same sources for flash points

Most popular data sources

Alfa Aesar donates melting points to the public

Open Melting Point Explorer

Outliers

MDPI dataset

EPI (via ChemSpider)

Outliers

Alfa Aesar

Inconsistencies and SMILES problems within MDPI dataset

MDPI Dataset labeled with High Trust Level

Open Melting Point Datasets

Open Random Forest modeling of Open Melting Point data using CDK descriptors

(Andrew Lang)

R2 = 0.78, TPSA and nHdon most important

Melting point prediction service

Other Web Services…

(Andrew Lang)

General Transparent Solubility Prediction

Convenient web services for solubility measurement and

prediction

(Andrew Lang)

Integration of Multiple Web Services to Recommend Solvents

for Reactions

(Andrew Lang)

Using melting point for temperature dependent solubility prediction

Semi-Automated Semi-Automated Measurement of solubility via Measurement of solubility via

web service analysis of web service analysis of JCAMP-DX files JCAMP-DX files

(Andy Lang)(Andy Lang)

Solubility Prediction (Andy Lang uses Abraham Model)

Reaction Attempts Book

Reaction Attempts Book: Reactants listed Alphabetically

Dynamic links to private tagged Mendeley collections

(Andrew Lang)

All ONS web services

For all Formats of ONS Projects

ONS Challenge Solubility Book cited for nanotechnology

application

Visualizing molecule-researcher connection maps reveals link between 2 Open Notebooks (Todd

and Bradley)

(Don Pellegrino)

The Intersection of Open Notebooks (Bradley/Todd) and IP implications

Open Notebook could have blocked patent

if done earlier

Decanoic acid

WaterNaCl

Phrase searching for useful solubility applications

Search for applications of solubility for breast cancer research

Solubility prediction for Taxol using Abraham descriptors

Pred Exp

Predicted temperature dependent solubility of Taxol in water (M)

Current research questions for Taxol solubility

1. Does Taxol have a meaningful solubility in methanol or does it decompose too quickly?

2. Why is methanol reported to decompose Taxol but not ethanol?

3. Can the solubility of Taxol in solvent mixtures be predicted, especially for approved excipients?

4. Can the solubility of Taxol analogs be used to create reliable models for the solubility of this class of compounds?

Moving Forward: Tools and Practices

Use free hosted web tools and open data formats

1. Google Spreadsheets (numerical data)2. Wikispaces (human readable format)3. YouTube, SlideShare, LuLu, Nature Precedings,

etc. (multiple data formats)4. JCAMP-DX for spectral data

Practices1. Report all findings immediately – even if tentative2. Participate in social media to share progress and

find collaborators3. Abstract experiments and findings to machine

readable formats and make these easily discoverable