Cleaning up chemistry for the pharma industry Delivering a flexible platform for interrogating the FDA DailyMed website Antony Williams

Vision Use the DailyMed FDA website data as a data source Use Microsoft Sharepoint Server as a platform to demonstrate integrated ChemSpider technology Deliver some “Chemistry” on the BioIT Alliance website Get funding to support ChemSpider

Use the DailyMed FDA website data as a data source

Use Microsoft Sharepoint Server as a platform to demonstrate integrated ChemSpider technology

Deliver some “Chemistry” on the BioIT Alliance website

Get funding to support ChemSpider

Reality

Chemistry on the Internet The Internet can clearly benefit chemists searching for information Much of the information is based on assertions and User Beware! The Quality of information available is diverse and how does the user know what is and is not “correct”?

The Internet can clearly benefit chemists searching for information

Much of the information is based on assertions and User Beware!

The Quality of information available is diverse and how does the user know what is and is not “correct”?

www.chemspider.com 21.5 million structures, 150 data sources and growing Flexible searching Deposition of structures, spectra, crowdsourced curation and annotation

21.5 million structures, 150 data sources and growing

Flexible searching

Deposition of structures, spectra, crowdsourced curation and annotation

Complex Data and Information

21.5 Million Structures, Varied Sources There are “bad structures” on the database There are bad structure-name pairs Users have associated “incorrect information”

There are “bad structures” on the database

There are bad structure-name pairs

Users have associated “incorrect information”

Data Curation

Caution! Question Everything!

Question Everything www.dhmo.org

Vancomycin Who will curate? PubChem is not resourced to clean these errors  How would you clean such a large dataset?

Who will curate?

PubChem is not resourced to clean these errors 

How would you clean such a large dataset?

Vancomycin ChemSpider: 1 compound – 3 days

DailyMed “ DailyMed provides high quality information about marketed drugs. This information includes FDA approved labels (package inserts).”

“ DailyMed provides high quality information about marketed drugs.

This information includes FDA approved labels (package inserts).”

The FDA’s DailyMed

The Intention Make DailyMed structure searchable via ChemSpider In the process curate data on ChemSpider and validate data on DailyMed Improve the curation platform on ChemSpider Perform markup of DailyMed articles to enhance the reading experience

Make DailyMed structure searchable via ChemSpider

In the process curate data on ChemSpider and validate data on DailyMed

Improve the curation platform on ChemSpider

Perform markup of DailyMed articles to enhance the reading experience

Structures on DailyMed Poor Representations

Structures on DailyMed Lack of Stereochemisty

Incorrect Structures Simply Wrong

Incorrect Structures Scanning (?) Issues

Incorrect Structures “HOO-BOY!!!!!”

Does it Matter? Does it matter to the consumer that the structures are wrong? No…what matters is what is in the bottle is the right medication! To make DailyMed structure searchable it DOES matter To data mine DailyMed it matters To mark up DailyMed it matters

Does it matter to the consumer that the structures are wrong? No…what matters is what is in the bottle is the right medication!

To make DailyMed structure searchable it DOES matter

To data mine DailyMed it matters

To mark up DailyMed it matters

The Process Import all XML files from DailyMed Use “Home built” entity extraction based on our dictionary of chemical names Articles online here: http://www.chemspider.com/DailyMed.aspx Example Article: http://www.chemspider.com/DailyMedArticle.aspx?id=2

Import all XML files from DailyMed

Use “Home built” entity extraction based on our dictionary of chemical names

Articles online here:

http://www.chemspider.com/DailyMed.aspx

Example Article: http://www.chemspider.com/DailyMedArticle.aspx?id=2

State of the Data

Tolinase: DailyMed on ChemSpider

OTHER Mentioned Chemicals

One Name – Multiple Structures NO Stereo Full Stereo Partial Stereo Partial Stereo

Editing a Record Do NOT deprecate record…remove association between name and chemical structure

Do NOT deprecate record…remove association between name and chemical structure

Partial Stereochemistry

Loop of Assertions Reduce to ONE structure – with full explicit stereo

Reduce to ONE structure – with full explicit stereo

How bad can it get??? And who is right????

Name-Structure Pairs Cleaning up the associations of names and structures is torturous and time-consuming Decisions get made and can be challenged Names are not “removed” …they are still on the database Such a curated “dictionary” is very valuable

Cleaning up the associations of names and structures is torturous and time-consuming

Decisions get made and can be challenged

Names are not “removed” …they are still on the database

Such a curated “dictionary” is very valuable

ChemMantis Chem ical M arkup A nd N omenclature T ransformation I ntegrated S ystem – ChemMantis A platform for entity extraction for chemistry documents, markup and integration to online information sources – Wikipedia, ChemSpider, Entrez… Web-based submission, markup and publishing platform now hosting the ChemSpider Journal of Chemistry

Chem ical M arkup A nd N omenclature T ransformation I ntegrated S ystem – ChemMantis

A platform for entity extraction for chemistry documents, markup and integration to online information sources – Wikipedia, ChemSpider, Entrez…

Web-based submission, markup and publishing platform now hosting the ChemSpider Journal of Chemistry

Back to DailyMed

Quality of Structures!!!

ChemMantis Markup

Species Markup

Dictionaries are Easily Enhanced Copy-Paste into appropriate Entity Dictionary Impacts all future markups Expanding knowledgebases of information Linked out to rich sources of information

Copy-Paste into appropriate Entity Dictionary

Impacts all future markups

Expanding knowledgebases of information

Linked out to rich sources of information

Outlinks…

Where To From Here? The platform is built…it’s all eyeballs for curation now As structure-identifier pairs are curated DailyMed will improve The project is now on hold – no resources to continue

The platform is built…it’s all eyeballs for curation now

As structure-identifier pairs are curated DailyMed will improve

The project is now on hold – no resources to continue

If We Had Our Way… Convert every DailyMed Label to a ChemMantis marked up document Use the XML segregation of the Tablet Labels to tag where chemicals are in the label Allow data mining based on “where” in a label the chemicals are..drug-drug interactions etc Markup and mine property data out of the labels using new dictionaries related to properties such as IC50 and toxicity

Convert every DailyMed Label to a ChemMantis marked up document

Use the XML segregation of the Tablet Labels to tag where chemicals are in the label

Allow data mining based on “where” in a label the chemicals are..drug-drug interactions etc

Markup and mine property data out of the labels using new dictionaries related to properties such as IC50 and toxicity

Conclusions The internet enables chemistry – and at a reduced cost Question Quality! All online information is suspect Crowdsourcing for expansion, curation and integration can both improve the quality of existing information and add new content If the FDA doesn’t have responsibility for what is on Tablet Labels…who does? The answer is simply an assertion!

The internet enables chemistry – and at a reduced cost

Question Quality! All online information is suspect

Crowdsourcing for expansion, curation and integration can both improve the quality of existing information and add new content

If the FDA doesn’t have responsibility for what is on Tablet Labels…who does? The answer is simply an assertion!

Interesting Sites ChemSpider http://www.chemspider.com ChemSpider Journal of Chemistry http://www.chemmantis.com The InChI resolver http://inchis.chemspider.com (goes live at ACS Spring) The ChemSpider blog http://www.chemspider.com/blog Contact [email_address]

ChemSpider

http://www.chemspider.com

ChemSpider Journal of Chemistry

http://www.chemmantis.com

The InChI resolver

http://inchis.chemspider.com (goes live at ACS Spring)

The ChemSpider blog

http://www.chemspider.com/blog

Contact

[email_address]