leveraging the value of documents content plexus for agile ......label inn/unn tradename drugcode...

Matthias Negri , PhDScientific Information CenterResearch Networking, Boehringer Ingelheim Pharma GmbH & Co KG

ChemAxon UGM, Budapest 2016 24. May 2016

Leveraging the value of documents content –PLEXUS for agile dissemination of results

Content

1. Data in Documents – beyond chemistry

2. Tools/technologies

3. Current (past) experiences - Patent Curation Workflow

4. What else..

5. Deployment of results – PLEXUS

6. Examples

2Negri M, ChemAxon UGM 2016

The manifold ways of Chemistry: Names …

InChI=1S/C22H30N6O4S/c1-5-7-17-19-20(27(4)25-17)22(29)24-21(23-19)16-14-15(8-9-18(16)32-6-2)33(30,31)28-12-10-26(3)11-13-28/h8-9,14H,5-7,10-13H2,1-4H3,(H,23,24,29)

InChIKey=BNRNXUUZRGQAQC-UHFFFAOYSA-N

CCCC1=NN(C)C2=C1N=C(NC2=O)C1=CC(=CC=C1OCC)S(=O)(=O)N1CCN(C)CC1

LabelINN/UNNTradeNameDrugCodeDrugNameCompanyCodeDBcode1, DBcode2,DBcode3, ….CDB codeDevelop.CodeProductCode…

IDMP code

バイアグラ

偉哥

Viagra

Sildenafil

5-{2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1H,6H,7H-pyrazolo[4,3-d]pyrimidin-7-one Compound 3


IUPAC:1‐methyl‐7‐(1‐methyl‐1H‐pyrazol‐4‐yl)‐5‐[4‐(trifluoromethoxy)phenyl]‐1H,4H,5H‐imidazo[4,5‐c]pyridin‐4‐one

text

molec. attachments (MOL,SDF, CDX)

table

table

image

example/cmpd nr

example/cmpd nr

The manifold ways of Chemistry: …appearance..


Drug indication,

Disease – condition,

Reaction types,

Mechanism of action,

Medicinal and off- targets,

Description,

contraindications,

side effects, AE,

DDI interactions,

drug group/type/classification,

sampling time per drug dose,

dosage history,

Bibliographic “novelty check”,

patent landscape,

safety

companies

Chemistry as linking node for all …data

Toxicity

The manifold ways of Chemistry: …data

PK/PD

Bioactivity

Other Data

and beyond Chemistry… PLENTY of DATA !


Phys-Chem Properties:- Experimental, calculated- Internal vs external

Content

1. Data in Documents – chemistry & beyond



4. What else.. can we do?

5. PLEXUS – use cases


Tools/technologies:The interplay

1. Pipelining - KNIME/XPATH

2. Chemical recognition - ChemAxon KNIME nodes + Command line tools

3. Text/data-mining – Linguamatics I2E

4. Optical Structure Recognition – Keymodule CLiDE

5. Visualization – ChemCurator and PLEXUS


Content




4. What else.. can we do?



SLOWER & memory intensive vs BUT Higher Quality, More Control & IUPAC-enriched XML

FASTER vs LESS informative/flexible

INPUT OCR TABLE

I2E API KNIME – Batch indexing, text-mining and (relational) data retrieval

GET

9

Current (past) experiences Patent Curation Workflow - update

Negri M, ChemAxon UGM 2016

Patent Curation WorkflowVisualize data-/textmining results

SDF file imported into ChemCC project + automatic mapping to existing chemistry

Tables are exported as Excel Sheets or as SDF files


1. Still NO full automation BUT: using KNIME’s flexibility - more workflows

2. Time & Computational Resources 8 CPU notebook + Server (needed in

particular for OCR correction routines)

3. Novelty checking: compare Preferred IUPAC vs Traditional names (incl. common)

4. Improved handling of OCR

11

Patent Curation Workflow - update


Content




4. Patents worked nice.. What else now?



1. Extraction of chemical reactions from PDFs

2. External databases – combine structured and unstructured (=TEXT) search

3. Internal Documents – make more out of Docx files

PLEXUSWhat’s next.. Visualization, Search & Share

Negri M, ChemAxon UGM 2016 13

1. Easy Search for chemical compounds or reaction in own PDF-collections

“Where is that reaction?“

2. Share your experience - Leverage in house synthetic knowledge

“Does this reaction also work when using a diverse reagent?“

“Which yield was achieved in house for that reaction?“

Extraction of chemical reactions from PDFs:

PLEXUS 1. Extract&Search for chemical reactions in PDFs


- Chemistry recognition (n2s/d2s, OSR)- linguistic reaction pattern recognition -

annotation with BRAT - Reaction extraction – splitting into components

Mrv file PLEXUSBrowser

PDF collection(s)


by



BRAT - capture the essence (role, anaphora, etc) of chemical reactions in text


Visualize/Design views for selected content – search & export results



19

PLEXUS 2. External databases – DrugBank

1. “classic” DB search (incl. chemical search) + search in “unstructured” text-boxes

2. Upload of content (eg. DrugBank) as raw XML/xls/csv or as pre-

processed/enriched nformation

3. Map DBs via IJC and display selected one2one/many-relations via PLEXUS

4. Custom Views for the various “customers“ within a company

Exploit Database-Searches beyond predefined fields:


PLEXUS 2. External databases – DrugBank

Substructure search

Text-based search


PLEXUS 3. Internal Documents – Docx/Doc

1. Search over 1000s of documents

2. Infer chemical meaning to Doc/Docx files

3. Extract&store bits of information company-wide repository for phys.-chem. or

experimental data

4. Outlook: combine “internal“ and external data

Make out more from static Word file collections (Dir:\file1, file2..)


IJCDesign

Form View

Text/datamining

Indexing/annotationFree text & tables

molconvert/reaction splitChemistry recognition (text + IMG/skc-Files)

join/mapCombine both outputs

PLEXUSVisualizeSearch




Different Tabs improved overview


- Version incompatibilities, stability issues, Java 7 vs Java 8

- If empty fields annoying error messages

PLEXUS - weak-points, limitations


- Only ONE chemical field – limited search options not possible to search for product and reagent in a “chemical” way




- Limited options - capabilities of IJC are not reflected in PLEXUS

Highlight search terms

HTML representation

IJC snapshot


Thank You

28

Acknowledgements

Lutz Weber

Anett Plüschel

Ulf Laube

Matthias Irmer

S.I.C. group

MedChem/ChemDev

H. Schmid

M. Santagostino

D. KirbergNegri M, ChemAxon UGM 2016