SlideShare a Scribd company logo
AGRO397 – ACS National Meeting – 29 August 2019
Dr Frederik van den Broek, Dr Maria Shkrob, Dr Anton Yuryev
Elsevier Professional Services
Finding novel lead
compounds in pesticide
discovery inspired by
pharmaceutical research
Publication trends on fungicide resistance
• Topic is on the rise
• High focus in the US
and UK
• Caution: not normalised
Publication trends on fungicide resistance
• Specifically for Botrytis
• Similar trend
• Different mix of
countries: most likely
those who have a
vested agricultural
interest
But that’s of course not the whole story
• Increasing awareness of toxic effects of conventional
formulations
• Try to increase efficacy by a more targeted approach for
a specific organism or class of organisms
• Find novel targets and modes of action to overcome
resistance
• Human Pharma to the rescue?
Image: https://www.amazon.co.uk/Thunderbirds-Rescue-Comic-Album/dp/1853044067
This is what we are all after in drug discovery…
Image: Elsevier
This is what we are all after in pesticide discovery…
Image: Elsevier
If drug discovery and development only were that simple…
Disease
Drug
compound
If drug discovery and development only were that simple…
Disease
Protein
Target
Drug
compound
If drug discovery and development only were that simple…
Disease
Protein
Target
Drug
compound
• Cell processes
• Regulators
• Pathways
• …
• Bioactivity
• Toxicity
• Specificity
• …
If drug discovery and development only were that simple…
Disease
Protein
Target
Drug
compound
• Cell processes
• Regulators
• Pathways
• …
• Bioactivity
• Toxicity
• Specificity
• …
• Availability
• Synthesis
• PK/PD
• …
• Genotype
• Phenotype
• Individual
If drug discovery and development only were that simple…
Disease
Protein
Target
Drug
compound
• Cell processes
• Regulators
• Pathways
• …
• Bioactivity
• Toxicity
• Specificity
• …
• Availability
• Synthesis
• PK/PD
• …
• Genotype
• Phenotype
• Individual
Accelerate with new knowledge and data
Disease
Protein
Target
Drug
compound
• Cell processes
• Regulators
• Pathways
• …
• Bioactivity
• Toxicity
• Specificity
• …
• Availability
• Synthesis
• PK/PD
• …
• Genotype
• Phenotype
• Individual
Project goals
Explore insights from anti-parasitic drug discovery:
• Targets used
• Chemicals used
To further explore applicability of those insights in
development of fungicides with a customer active in the crop
protection business.
Proof of Concept model:
• Parasite: Plasmodium falciparum
• Fungal species: Botryotinia fuckeliana and
Zymoseptoria tritici
• Target – any protein involved
Images:
CDC/Dr. Mae Melvin (PHIL #2704), 1973 / https://en.wikipedia.org/wiki/Plasmodium_falciparum
http://www.agroatlas.ru/en/content/diseases/Olee/Olee_Botrytis_cinerea/
https://commons.wikimedia.org/wiki/File:Septoria-tritici.jpg
Strategy to follow
• Find out which small molecules interact with
Plasmodium falciparum targets
− Use database of bioactivity data mined and
extracted from literature and patents to get pre-
extracted information about proteins from
Plasmodium falciparum
• Find out which proteins in fungi are homologs to
Plasmodium falciparum targets
− Build homology maps between fungi and
Plasmodium falciparum
Image: Elsevier
Project overview
Database of
known targets
and active
compounds for
malaria parasite
Map to parasite genes
using MedScan (NLP
engine)
Ortholog mapping to
fungal genes using
Blastp
Candidate
compounds
affecting fungal
targets
Parasite
gene
sequence
Fungus
gene
sequence
Biology
literature
full text
Custom dictionary development
Pf genes
NCBI
gene
Pf
proteins
UniProt
mapped by
GeneID
Unique names,
synonyms
Pf genes
with
synonyms
Functional
classes
Pf dictionary
Mammal,
Plant
dictionary
mapped by
MedScan
Duplicates
• Slowest stage due to manual
curation
• NCBI gene annotations range
from specific to very broad,
curation needed to remove
ambiguous terms / synonyms
• Functional classes – terms
corresponding to more that
one Pf ID
Mapping to fungal genes
Aminoacid sequences from RefSeq:
best reciprocal hit method based on full-
length BLAST alignments
Plasmodium falciparum  Yeast  Fungi
• Botryotinia fuckeliana – 845
• Zymoseptoria tritici – 866
For more details on the method followed:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1160523/
Now all the plumbing is ready
Database of
known targets
and active
compounds for
malaria parasite
Map to parasite genes
using MedScan (NLP
engine)
Ortholog mapping to
fungal genes using
Blastp
Candidate
compounds
affecting fungal
targets
Parasite
gene
sequence
Fungus
gene
sequence
Biology
literature
full text
Bioactivity data in Reaxys Medicinal Chemistry
>35.2 Million
bioactivity data
points
>6.8 Million
compounds with
bioactivity
>27,000
total targets
>65,000
chemical species
>133,000
medicinal chemistry
patents
>370,000
medicinal chemistry
articles and others
>5,000
drug discovery and
pharma journals
The database contains
This data is sourced from
Plasmodium bioassay data target mapping
Unique compounds after mapping to fungi
~3500 ~1550
Botryotinia fuckeliana Zymoseptoria tritici
Top fungal targets with active compounds
A number of compounds were already found to be active against the fungi
Target, Botryotinia 6-7 7-8 8-9 9-10 10-11 no data
Grand
Total
Plasmepsin-2 194 376 135 21 15 640 1641
Dihydroorotate dehydrogenase (quinone), mitochondrial 135 66 2 315 1025
L-lactate dehydrogenase 61 7 4 212
Plasmepsin-1 22 35 19 10 38 163
Deoxyuridine 5'-triphosphate nucleotidohydrolase 24 3 10 127
Glutathione S-transferase 80 104
Thioredoxin reductase 1, mitochondrial 8 21 63
Histone deacetylase 1 8 13 6 3 8 46
Adenosylhomocysteinase 1 1 15 29
Histone deacetylase 1 3 10 15
Target, Zymoseptoria 6-7 7-8 8-9 9-10 10-11 no data
Grand
Total
Dihydroorotate dehydrogenase (quinone), mitochondrial 135 66 2 315 1025
Plasmepsin IV 14 12 9 9 1 90 175
Plasmepsin-1 22 35 19 10 38 163
Histone deacetylase 1 8 13 6 3 8 46
orotidine-5'-phosphate decarboxylase 1 1 2 4 38
ATPase, Ca++ Transporting, Plasma Membrane 1 9 2 16
Histone deacetylase 1 3 10 15
Aminopeptidase N 4 1 1 12
3-Oxoacyl-(Acyl Carrier Protein) Synthase II 11
3-Oxoacyl-(Acyl Carrier Protein) Synthase I 11
Conclusions
• Successfully able to map Plasmodium targets and active compounds to
find already known and new candidate compounds against fungal targets.
• Mapping target names from literature to parasite genes is an essential
step (but labour intensive step) to reduce the noise.
• Once parasite dictionary and mapping is built, the process can be
repeated for many different fungi
Questions?
• Can also be asked later: f.broek@elsevier.com
• LinkedIn: https://www.linkedin.com/in/frederik-van-den-broek/
By Malis - https://commons.wikimedia.org/w/index.php?curid=2633354

More Related Content

What's hot

Capturing BIA-10-2474 and related FAAH inhibitor data
Capturing BIA-10-2474 and related FAAH inhibitor dataCapturing BIA-10-2474 and related FAAH inhibitor data
Capturing BIA-10-2474 and related FAAH inhibitor data
Chris Southan
 
Patent chemisty big bang: utilities for SMEs
Patent chemisty big bang: utilities for SMEsPatent chemisty big bang: utilities for SMEs
Patent chemisty big bang: utilities for SMEs
Chris Southan
 
GtoPdb and GtoImmuPdb in context
GtoPdb and GtoImmuPdb in contextGtoPdb and GtoImmuPdb in context
GtoPdb and GtoImmuPdb in context
Chris Southan
 
IUPHAR/BPS Guide to Pharmacology: concise mapping of chemistry, data, and tar...
IUPHAR/BPS Guide to Pharmacology: concise mapping of chemistry, data, and tar...IUPHAR/BPS Guide to Pharmacology: concise mapping of chemistry, data, and tar...
IUPHAR/BPS Guide to Pharmacology: concise mapping of chemistry, data, and tar...
Chris Southan
 
PubChem for chemical information literacy training
PubChem for chemical information literacy trainingPubChem for chemical information literacy training
PubChem for chemical information literacy training
Sunghwan Kim
 
Toxicological information in PubChem
Toxicological information in PubChemToxicological information in PubChem
Toxicological information in PubChem
Sunghwan Kim
 
Generating Biomedical Hypotheses Using Semantic Web Technologies
Generating Biomedical Hypotheses Using Semantic Web TechnologiesGenerating Biomedical Hypotheses Using Semantic Web Technologies
Generating Biomedical Hypotheses Using Semantic Web Technologies
Michel Dumontier
 
BIA 10-2474 in GtoPdb
BIA 10-2474 in GtoPdbBIA 10-2474 in GtoPdb
BIA 10-2474 in GtoPdb
Chris Southan
 
Searching for patent information in PubChem
Searching for patent information in PubChem Searching for patent information in PubChem
Searching for patent information in PubChem
Sunghwan Kim
 
PubChem: a public chemical information resource for big data chemistry
PubChem: a public chemical information resource for big data chemistryPubChem: a public chemical information resource for big data chemistry
PubChem: a public chemical information resource for big data chemistry
Sunghwan Kim
 
Online Resources to Support Open Drug Discovery Systems
Online Resources to Support Open Drug Discovery SystemsOnline Resources to Support Open Drug Discovery Systems
Pubchem
PubchemPubchem
Pubchem
samantlalit
 
Connecting antimalarial data
Connecting antimalarial dataConnecting antimalarial data
Connecting antimalarial data
Chris Southan
 
Searching for chemical information using PubChem
Searching for chemical information using PubChemSearching for chemical information using PubChem
Searching for chemical information using PubChem
Sunghwan Kim
 
Health Datapalooza 2013: Datalab - Steven Edwards
Health Datapalooza 2013: Datalab - Steven EdwardsHealth Datapalooza 2013: Datalab - Steven Edwards
Health Datapalooza 2013: Datalab - Steven Edwards
Health Data Consortium
 
PubChem and its application for cheminformatics education
PubChem and its application for cheminformatics educationPubChem and its application for cheminformatics education
PubChem and its application for cheminformatics education
Sunghwan Kim
 
How can you access PubChem programmatically?
How can you access PubChem programmatically?How can you access PubChem programmatically?
How can you access PubChem programmatically?
Sunghwan Kim
 
2011-10-11 Open PHACTS at BioIT World Europe
2011-10-11 Open PHACTS at BioIT World Europe2011-10-11 Open PHACTS at BioIT World Europe
2011-10-11 Open PHACTS at BioIT World Europe
open_phacts
 
ABT 609 PPT
ABT 609 PPTABT 609 PPT
ABT 609 PPT
Jane Awah
 
Guide to Pharmacology Poster - ELIXIR All Hands 2020
Guide to Pharmacology Poster - ELIXIR All Hands 2020Guide to Pharmacology Poster - ELIXIR All Hands 2020
Guide to Pharmacology Poster - ELIXIR All Hands 2020
Guide to PHARMACOLOGY
 

What's hot (20)

Capturing BIA-10-2474 and related FAAH inhibitor data
Capturing BIA-10-2474 and related FAAH inhibitor dataCapturing BIA-10-2474 and related FAAH inhibitor data
Capturing BIA-10-2474 and related FAAH inhibitor data
 
Patent chemisty big bang: utilities for SMEs
Patent chemisty big bang: utilities for SMEsPatent chemisty big bang: utilities for SMEs
Patent chemisty big bang: utilities for SMEs
 
GtoPdb and GtoImmuPdb in context
GtoPdb and GtoImmuPdb in contextGtoPdb and GtoImmuPdb in context
GtoPdb and GtoImmuPdb in context
 
IUPHAR/BPS Guide to Pharmacology: concise mapping of chemistry, data, and tar...
IUPHAR/BPS Guide to Pharmacology: concise mapping of chemistry, data, and tar...IUPHAR/BPS Guide to Pharmacology: concise mapping of chemistry, data, and tar...
IUPHAR/BPS Guide to Pharmacology: concise mapping of chemistry, data, and tar...
 
PubChem for chemical information literacy training
PubChem for chemical information literacy trainingPubChem for chemical information literacy training
PubChem for chemical information literacy training
 
Toxicological information in PubChem
Toxicological information in PubChemToxicological information in PubChem
Toxicological information in PubChem
 
Generating Biomedical Hypotheses Using Semantic Web Technologies
Generating Biomedical Hypotheses Using Semantic Web TechnologiesGenerating Biomedical Hypotheses Using Semantic Web Technologies
Generating Biomedical Hypotheses Using Semantic Web Technologies
 
BIA 10-2474 in GtoPdb
BIA 10-2474 in GtoPdbBIA 10-2474 in GtoPdb
BIA 10-2474 in GtoPdb
 
Searching for patent information in PubChem
Searching for patent information in PubChem Searching for patent information in PubChem
Searching for patent information in PubChem
 
PubChem: a public chemical information resource for big data chemistry
PubChem: a public chemical information resource for big data chemistryPubChem: a public chemical information resource for big data chemistry
PubChem: a public chemical information resource for big data chemistry
 
Online Resources to Support Open Drug Discovery Systems
Online Resources to Support Open Drug Discovery SystemsOnline Resources to Support Open Drug Discovery Systems
Online Resources to Support Open Drug Discovery Systems
 
Pubchem
PubchemPubchem
Pubchem
 
Connecting antimalarial data
Connecting antimalarial dataConnecting antimalarial data
Connecting antimalarial data
 
Searching for chemical information using PubChem
Searching for chemical information using PubChemSearching for chemical information using PubChem
Searching for chemical information using PubChem
 
Health Datapalooza 2013: Datalab - Steven Edwards
Health Datapalooza 2013: Datalab - Steven EdwardsHealth Datapalooza 2013: Datalab - Steven Edwards
Health Datapalooza 2013: Datalab - Steven Edwards
 
PubChem and its application for cheminformatics education
PubChem and its application for cheminformatics educationPubChem and its application for cheminformatics education
PubChem and its application for cheminformatics education
 
How can you access PubChem programmatically?
How can you access PubChem programmatically?How can you access PubChem programmatically?
How can you access PubChem programmatically?
 
2011-10-11 Open PHACTS at BioIT World Europe
2011-10-11 Open PHACTS at BioIT World Europe2011-10-11 Open PHACTS at BioIT World Europe
2011-10-11 Open PHACTS at BioIT World Europe
 
ABT 609 PPT
ABT 609 PPTABT 609 PPT
ABT 609 PPT
 
Guide to Pharmacology Poster - ELIXIR All Hands 2020
Guide to Pharmacology Poster - ELIXIR All Hands 2020Guide to Pharmacology Poster - ELIXIR All Hands 2020
Guide to Pharmacology Poster - ELIXIR All Hands 2020
 

Similar to Finding novel lead compounds in pesticide discovery inspired by pharmaceutical research (AGRO 397, ACS National Meeting 2019-08-29)

Bioinformatics
BioinformaticsBioinformatics
Bioinformatics
Dr. Siddhi Upadhyay
 
Drug discovery and development
Drug discovery and developmentDrug discovery and development
Drug discovery and development
rahul_pharma
 
Drug discovery and development. Introducing
Drug discovery and development. IntroducingDrug discovery and development. Introducing
Drug discovery and development. Introducing
7ReeshabhBele
 
Drug discovery and development
Drug discovery and developmentDrug discovery and development
Drug discovery and development
rahul_pharma
 
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptxPRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
DharaMehta45
 
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptxPRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
DharaMehta45
 
DRUG discovery
DRUG discoveryDRUG discovery
DRUG discovery
Gopal Agrawal
 
IUPHAR/MMV Guide to Malaria Pharmacology - BioMalPar XV
IUPHAR/MMV Guide to Malaria Pharmacology - BioMalPar XVIUPHAR/MMV Guide to Malaria Pharmacology - BioMalPar XV
IUPHAR/MMV Guide to Malaria Pharmacology - BioMalPar XV
Guide to PHARMACOLOGY
 
Nw biotech fundamentals day 2 session 1 introduction
Nw biotech fundamentals day 2 session 1   introductionNw biotech fundamentals day 2 session 1   introduction
Nw biotech fundamentals day 2 session 1 introduction
Nicholas Weston Lawyers
 
plant made pharmaceuticals seminar by manju cp
plant made pharmaceuticals seminar by manju cp plant made pharmaceuticals seminar by manju cp
plant made pharmaceuticals seminar by manju cp
manju paloti
 
Dr. Rick Sibbel - Pharmaceutical Industry Perspective of the Impacts of the R...
Dr. Rick Sibbel - Pharmaceutical Industry Perspective of the Impacts of the R...Dr. Rick Sibbel - Pharmaceutical Industry Perspective of the Impacts of the R...
Dr. Rick Sibbel - Pharmaceutical Industry Perspective of the Impacts of the R...
John Blue
 
Drug discovery
Drug discoveryDrug discovery
Drug discovery
Saba Ahmed
 
Antibiotics gl.pptx
Antibiotics gl.pptxAntibiotics gl.pptx
DRUG DISCOVERY :TRADITIONAL VS RATIONAL DRUG DESIGN
DRUG DISCOVERY :TRADITIONAL VS RATIONAL DRUG DESIGNDRUG DISCOVERY :TRADITIONAL VS RATIONAL DRUG DESIGN
DRUG DISCOVERY :TRADITIONAL VS RATIONAL DRUG DESIGN
AADYARAJPANDEY1
 
Drug Development method by responsees .ppt
Drug Development method by responsees   .pptDrug Development method by responsees   .ppt
Drug Development method by responsees .ppt
AdnanSarwar43
 
Better Biotech Innovation by Improving the Ecosystem by Tim Charlebois, VP In...
Better Biotech Innovation by Improving the Ecosystem by Tim Charlebois, VP In...Better Biotech Innovation by Improving the Ecosystem by Tim Charlebois, VP In...
Better Biotech Innovation by Improving the Ecosystem by Tim Charlebois, VP In...
MIT Startup Exchange
 
Dr. Larry Granger - USDA Antimicrobial Resistance Strategy
Dr. Larry Granger - USDA Antimicrobial Resistance StrategyDr. Larry Granger - USDA Antimicrobial Resistance Strategy
Dr. Larry Granger - USDA Antimicrobial Resistance Strategy
John Blue
 
Requesting a complete biosensor system in phyto-sourced drug discovery and de...
Requesting a complete biosensor system in phyto-sourced drug discovery and de...Requesting a complete biosensor system in phyto-sourced drug discovery and de...
Requesting a complete biosensor system in phyto-sourced drug discovery and de...
iosrphr_editor
 
Drugdiscoveryanddevelopment by khadga raj
Drugdiscoveryanddevelopment by khadga rajDrugdiscoveryanddevelopment by khadga raj
Drugdiscoveryanddevelopment by khadga raj
Khadga Raj
 
Introduction to Gene Mining Part A: BLASTn-off!
Introduction to Gene Mining Part A: BLASTn-off!Introduction to Gene Mining Part A: BLASTn-off!
Introduction to Gene Mining Part A: BLASTn-off!
adcobb
 

Similar to Finding novel lead compounds in pesticide discovery inspired by pharmaceutical research (AGRO 397, ACS National Meeting 2019-08-29) (20)

Bioinformatics
BioinformaticsBioinformatics
Bioinformatics
 
Drug discovery and development
Drug discovery and developmentDrug discovery and development
Drug discovery and development
 
Drug discovery and development. Introducing
Drug discovery and development. IntroducingDrug discovery and development. Introducing
Drug discovery and development. Introducing
 
Drug discovery and development
Drug discovery and developmentDrug discovery and development
Drug discovery and development
 
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptxPRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
 
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptxPRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
PRINCIPLES OF DRUG DISCOVERY & DEVELOPMENT.pptx
 
DRUG discovery
DRUG discoveryDRUG discovery
DRUG discovery
 
IUPHAR/MMV Guide to Malaria Pharmacology - BioMalPar XV
IUPHAR/MMV Guide to Malaria Pharmacology - BioMalPar XVIUPHAR/MMV Guide to Malaria Pharmacology - BioMalPar XV
IUPHAR/MMV Guide to Malaria Pharmacology - BioMalPar XV
 
Nw biotech fundamentals day 2 session 1 introduction
Nw biotech fundamentals day 2 session 1   introductionNw biotech fundamentals day 2 session 1   introduction
Nw biotech fundamentals day 2 session 1 introduction
 
plant made pharmaceuticals seminar by manju cp
plant made pharmaceuticals seminar by manju cp plant made pharmaceuticals seminar by manju cp
plant made pharmaceuticals seminar by manju cp
 
Dr. Rick Sibbel - Pharmaceutical Industry Perspective of the Impacts of the R...
Dr. Rick Sibbel - Pharmaceutical Industry Perspective of the Impacts of the R...Dr. Rick Sibbel - Pharmaceutical Industry Perspective of the Impacts of the R...
Dr. Rick Sibbel - Pharmaceutical Industry Perspective of the Impacts of the R...
 
Drug discovery
Drug discoveryDrug discovery
Drug discovery
 
Antibiotics gl.pptx
Antibiotics gl.pptxAntibiotics gl.pptx
Antibiotics gl.pptx
 
DRUG DISCOVERY :TRADITIONAL VS RATIONAL DRUG DESIGN
DRUG DISCOVERY :TRADITIONAL VS RATIONAL DRUG DESIGNDRUG DISCOVERY :TRADITIONAL VS RATIONAL DRUG DESIGN
DRUG DISCOVERY :TRADITIONAL VS RATIONAL DRUG DESIGN
 
Drug Development method by responsees .ppt
Drug Development method by responsees   .pptDrug Development method by responsees   .ppt
Drug Development method by responsees .ppt
 
Better Biotech Innovation by Improving the Ecosystem by Tim Charlebois, VP In...
Better Biotech Innovation by Improving the Ecosystem by Tim Charlebois, VP In...Better Biotech Innovation by Improving the Ecosystem by Tim Charlebois, VP In...
Better Biotech Innovation by Improving the Ecosystem by Tim Charlebois, VP In...
 
Dr. Larry Granger - USDA Antimicrobial Resistance Strategy
Dr. Larry Granger - USDA Antimicrobial Resistance StrategyDr. Larry Granger - USDA Antimicrobial Resistance Strategy
Dr. Larry Granger - USDA Antimicrobial Resistance Strategy
 
Requesting a complete biosensor system in phyto-sourced drug discovery and de...
Requesting a complete biosensor system in phyto-sourced drug discovery and de...Requesting a complete biosensor system in phyto-sourced drug discovery and de...
Requesting a complete biosensor system in phyto-sourced drug discovery and de...
 
Drugdiscoveryanddevelopment by khadga raj
Drugdiscoveryanddevelopment by khadga rajDrugdiscoveryanddevelopment by khadga raj
Drugdiscoveryanddevelopment by khadga raj
 
Introduction to Gene Mining Part A: BLASTn-off!
Introduction to Gene Mining Part A: BLASTn-off!Introduction to Gene Mining Part A: BLASTn-off!
Introduction to Gene Mining Part A: BLASTn-off!
 

Recently uploaded

Biometric Question Bank 2021 - 1 Soln-1.pdf
Biometric Question Bank 2021 - 1 Soln-1.pdfBiometric Question Bank 2021 - 1 Soln-1.pdf
Biometric Question Bank 2021 - 1 Soln-1.pdf
Joel Ngushwai
 
Exclusive Girls Call Noida 🎈🔥9873940964 🔥💋🎈 Provide Best And Top Girl Service...
Exclusive Girls Call Noida 🎈🔥9873940964 🔥💋🎈 Provide Best And Top Girl Service...Exclusive Girls Call Noida 🎈🔥9873940964 🔥💋🎈 Provide Best And Top Girl Service...
Exclusive Girls Call Noida 🎈🔥9873940964 🔥💋🎈 Provide Best And Top Girl Service...
sheetal singh$A17
 
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
ginni singh$A17
 
Oracle Database Desupported Features on 23ai (Part B)
Oracle Database Desupported Features on 23ai (Part B)Oracle Database Desupported Features on 23ai (Part B)
Oracle Database Desupported Features on 23ai (Part B)
Alireza Kamrani
 
New Girls Call Delhi 🎈🔥9711199171 🔥💋🎈 Provide Best And Top Girl Service And N...
New Girls Call Delhi 🎈🔥9711199171 🔥💋🎈 Provide Best And Top Girl Service And N...New Girls Call Delhi 🎈🔥9711199171 🔥💋🎈 Provide Best And Top Girl Service And N...
New Girls Call Delhi 🎈🔥9711199171 🔥💋🎈 Provide Best And Top Girl Service And N...
tanupasswan6
 
VIP Kanpur Girls Call Kanpur 0X0000000X Doorstep High-Profile Girl Service Ca...
VIP Kanpur Girls Call Kanpur 0X0000000X Doorstep High-Profile Girl Service Ca...VIP Kanpur Girls Call Kanpur 0X0000000X Doorstep High-Profile Girl Service Ca...
VIP Kanpur Girls Call Kanpur 0X0000000X Doorstep High-Profile Girl Service Ca...
satpalsheravatmumbai
 
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
ginni singh$A17
 
Solution Manual for First Course in Abstract Algebra A, 8th Edition by John B...
Solution Manual for First Course in Abstract Algebra A, 8th Edition by John B...Solution Manual for First Course in Abstract Algebra A, 8th Edition by John B...
Solution Manual for First Course in Abstract Algebra A, 8th Edition by John B...
rightmanforbloodline
 
Celebrity Girls Call Andheri 9930245274 Unlimited Short Providing Girls Servi...
Celebrity Girls Call Andheri 9930245274 Unlimited Short Providing Girls Servi...Celebrity Girls Call Andheri 9930245274 Unlimited Short Providing Girls Servi...
Celebrity Girls Call Andheri 9930245274 Unlimited Short Providing Girls Servi...
revolutionary575
 
Coimbatore Girls call Service 000XX00000 Provide Best And Top Girl Service An...
Coimbatore Girls call Service 000XX00000 Provide Best And Top Girl Service An...Coimbatore Girls call Service 000XX00000 Provide Best And Top Girl Service An...
Coimbatore Girls call Service 000XX00000 Provide Best And Top Girl Service An...
vrvipin164
 
History and Application of LLM Leveraging Big Data
History and Application of LLM Leveraging Big DataHistory and Application of LLM Leveraging Big Data
History and Application of LLM Leveraging Big Data
Jongwook Woo
 
DU degree offer diploma Transcript
DU degree offer diploma TranscriptDU degree offer diploma Transcript
DU degree offer diploma Transcript
uapta
 
Beautiful Girls Call Pune 000XX00000 Provide Best And Top Girl Service And No...
Beautiful Girls Call Pune 000XX00000 Provide Best And Top Girl Service And No...Beautiful Girls Call Pune 000XX00000 Provide Best And Top Girl Service And No...
Beautiful Girls Call Pune 000XX00000 Provide Best And Top Girl Service And No...
birajmohan012
 
Premium Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Ser...
Premium Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Ser...Premium Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Ser...
Premium Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Ser...
6459astrid
 
🚂🚘 Premium Girls Call Bangalore 🛵🚡000XX00000 💃 Choose Best And Top Girl Serv...
🚂🚘 Premium Girls Call Bangalore  🛵🚡000XX00000 💃 Choose Best And Top Girl Serv...🚂🚘 Premium Girls Call Bangalore  🛵🚡000XX00000 💃 Choose Best And Top Girl Serv...
🚂🚘 Premium Girls Call Bangalore 🛵🚡000XX00000 💃 Choose Best And Top Girl Serv...
bhupeshkumar0889
 
社内勉強会資料_TransNeXt: Robust Foveal Visual Perception for Vision Transformers
社内勉強会資料_TransNeXt: Robust Foveal Visual Perception for Vision Transformers社内勉強会資料_TransNeXt: Robust Foveal Visual Perception for Vision Transformers
社内勉強会資料_TransNeXt: Robust Foveal Visual Perception for Vision Transformers
NABLAS株式会社
 
Why_are_we_hypnotizing_ourselves-_ATeggin-1.pdf
Why_are_we_hypnotizing_ourselves-_ATeggin-1.pdfWhy_are_we_hypnotizing_ourselves-_ATeggin-1.pdf
Why_are_we_hypnotizing_ourselves-_ATeggin-1.pdf
Alexander Teggin
 
Beautiful Girls Call 9711199171 9711199171 Provide Best And Top Girl Service ...
Beautiful Girls Call 9711199171 9711199171 Provide Best And Top Girl Service ...Beautiful Girls Call 9711199171 9711199171 Provide Best And Top Girl Service ...
Beautiful Girls Call 9711199171 9711199171 Provide Best And Top Girl Service ...
janvikumar4133
 
Girls call in Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 ...
Girls call in Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 ...Girls call in Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 ...
Girls call in Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 ...
avanikakapoor
 
CHAPTER-1-Introduction-to-Marketing.pptx
CHAPTER-1-Introduction-to-Marketing.pptxCHAPTER-1-Introduction-to-Marketing.pptx
CHAPTER-1-Introduction-to-Marketing.pptx
girewiy968
 

Recently uploaded (20)

Biometric Question Bank 2021 - 1 Soln-1.pdf
Biometric Question Bank 2021 - 1 Soln-1.pdfBiometric Question Bank 2021 - 1 Soln-1.pdf
Biometric Question Bank 2021 - 1 Soln-1.pdf
 
Exclusive Girls Call Noida 🎈🔥9873940964 🔥💋🎈 Provide Best And Top Girl Service...
Exclusive Girls Call Noida 🎈🔥9873940964 🔥💋🎈 Provide Best And Top Girl Service...Exclusive Girls Call Noida 🎈🔥9873940964 🔥💋🎈 Provide Best And Top Girl Service...
Exclusive Girls Call Noida 🎈🔥9873940964 🔥💋🎈 Provide Best And Top Girl Service...
 
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
 
Oracle Database Desupported Features on 23ai (Part B)
Oracle Database Desupported Features on 23ai (Part B)Oracle Database Desupported Features on 23ai (Part B)
Oracle Database Desupported Features on 23ai (Part B)
 
New Girls Call Delhi 🎈🔥9711199171 🔥💋🎈 Provide Best And Top Girl Service And N...
New Girls Call Delhi 🎈🔥9711199171 🔥💋🎈 Provide Best And Top Girl Service And N...New Girls Call Delhi 🎈🔥9711199171 🔥💋🎈 Provide Best And Top Girl Service And N...
New Girls Call Delhi 🎈🔥9711199171 🔥💋🎈 Provide Best And Top Girl Service And N...
 
VIP Kanpur Girls Call Kanpur 0X0000000X Doorstep High-Profile Girl Service Ca...
VIP Kanpur Girls Call Kanpur 0X0000000X Doorstep High-Profile Girl Service Ca...VIP Kanpur Girls Call Kanpur 0X0000000X Doorstep High-Profile Girl Service Ca...
VIP Kanpur Girls Call Kanpur 0X0000000X Doorstep High-Profile Girl Service Ca...
 
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
Celebrity Girls Call Noida 9873940964 Unlimited Short Providing Girls Service...
 
Solution Manual for First Course in Abstract Algebra A, 8th Edition by John B...
Solution Manual for First Course in Abstract Algebra A, 8th Edition by John B...Solution Manual for First Course in Abstract Algebra A, 8th Edition by John B...
Solution Manual for First Course in Abstract Algebra A, 8th Edition by John B...
 
Celebrity Girls Call Andheri 9930245274 Unlimited Short Providing Girls Servi...
Celebrity Girls Call Andheri 9930245274 Unlimited Short Providing Girls Servi...Celebrity Girls Call Andheri 9930245274 Unlimited Short Providing Girls Servi...
Celebrity Girls Call Andheri 9930245274 Unlimited Short Providing Girls Servi...
 
Coimbatore Girls call Service 000XX00000 Provide Best And Top Girl Service An...
Coimbatore Girls call Service 000XX00000 Provide Best And Top Girl Service An...Coimbatore Girls call Service 000XX00000 Provide Best And Top Girl Service An...
Coimbatore Girls call Service 000XX00000 Provide Best And Top Girl Service An...
 
History and Application of LLM Leveraging Big Data
History and Application of LLM Leveraging Big DataHistory and Application of LLM Leveraging Big Data
History and Application of LLM Leveraging Big Data
 
DU degree offer diploma Transcript
DU degree offer diploma TranscriptDU degree offer diploma Transcript
DU degree offer diploma Transcript
 
Beautiful Girls Call Pune 000XX00000 Provide Best And Top Girl Service And No...
Beautiful Girls Call Pune 000XX00000 Provide Best And Top Girl Service And No...Beautiful Girls Call Pune 000XX00000 Provide Best And Top Girl Service And No...
Beautiful Girls Call Pune 000XX00000 Provide Best And Top Girl Service And No...
 
Premium Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Ser...
Premium Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Ser...Premium Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Ser...
Premium Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Ser...
 
🚂🚘 Premium Girls Call Bangalore 🛵🚡000XX00000 💃 Choose Best And Top Girl Serv...
🚂🚘 Premium Girls Call Bangalore  🛵🚡000XX00000 💃 Choose Best And Top Girl Serv...🚂🚘 Premium Girls Call Bangalore  🛵🚡000XX00000 💃 Choose Best And Top Girl Serv...
🚂🚘 Premium Girls Call Bangalore 🛵🚡000XX00000 💃 Choose Best And Top Girl Serv...
 
社内勉強会資料_TransNeXt: Robust Foveal Visual Perception for Vision Transformers
社内勉強会資料_TransNeXt: Robust Foveal Visual Perception for Vision Transformers社内勉強会資料_TransNeXt: Robust Foveal Visual Perception for Vision Transformers
社内勉強会資料_TransNeXt: Robust Foveal Visual Perception for Vision Transformers
 
Why_are_we_hypnotizing_ourselves-_ATeggin-1.pdf
Why_are_we_hypnotizing_ourselves-_ATeggin-1.pdfWhy_are_we_hypnotizing_ourselves-_ATeggin-1.pdf
Why_are_we_hypnotizing_ourselves-_ATeggin-1.pdf
 
Beautiful Girls Call 9711199171 9711199171 Provide Best And Top Girl Service ...
Beautiful Girls Call 9711199171 9711199171 Provide Best And Top Girl Service ...Beautiful Girls Call 9711199171 9711199171 Provide Best And Top Girl Service ...
Beautiful Girls Call 9711199171 9711199171 Provide Best And Top Girl Service ...
 
Girls call in Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 ...
Girls call in Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 ...Girls call in Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 ...
Girls call in Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 ...
 
CHAPTER-1-Introduction-to-Marketing.pptx
CHAPTER-1-Introduction-to-Marketing.pptxCHAPTER-1-Introduction-to-Marketing.pptx
CHAPTER-1-Introduction-to-Marketing.pptx
 

Finding novel lead compounds in pesticide discovery inspired by pharmaceutical research (AGRO 397, ACS National Meeting 2019-08-29)

  • 1. AGRO397 – ACS National Meeting – 29 August 2019 Dr Frederik van den Broek, Dr Maria Shkrob, Dr Anton Yuryev Elsevier Professional Services Finding novel lead compounds in pesticide discovery inspired by pharmaceutical research
  • 2. Publication trends on fungicide resistance • Topic is on the rise • High focus in the US and UK • Caution: not normalised
  • 3. Publication trends on fungicide resistance • Specifically for Botrytis • Similar trend • Different mix of countries: most likely those who have a vested agricultural interest
  • 4. But that’s of course not the whole story • Increasing awareness of toxic effects of conventional formulations • Try to increase efficacy by a more targeted approach for a specific organism or class of organisms • Find novel targets and modes of action to overcome resistance • Human Pharma to the rescue? Image: https://www.amazon.co.uk/Thunderbirds-Rescue-Comic-Album/dp/1853044067
  • 5. This is what we are all after in drug discovery… Image: Elsevier
  • 6. This is what we are all after in pesticide discovery… Image: Elsevier
  • 7. If drug discovery and development only were that simple… Disease Drug compound
  • 8. If drug discovery and development only were that simple… Disease Protein Target Drug compound
  • 9. If drug discovery and development only were that simple… Disease Protein Target Drug compound • Cell processes • Regulators • Pathways • … • Bioactivity • Toxicity • Specificity • …
  • 10. If drug discovery and development only were that simple… Disease Protein Target Drug compound • Cell processes • Regulators • Pathways • … • Bioactivity • Toxicity • Specificity • … • Availability • Synthesis • PK/PD • … • Genotype • Phenotype • Individual
  • 11. If drug discovery and development only were that simple… Disease Protein Target Drug compound • Cell processes • Regulators • Pathways • … • Bioactivity • Toxicity • Specificity • … • Availability • Synthesis • PK/PD • … • Genotype • Phenotype • Individual
  • 12. Accelerate with new knowledge and data Disease Protein Target Drug compound • Cell processes • Regulators • Pathways • … • Bioactivity • Toxicity • Specificity • … • Availability • Synthesis • PK/PD • … • Genotype • Phenotype • Individual
  • 13. Project goals Explore insights from anti-parasitic drug discovery: • Targets used • Chemicals used To further explore applicability of those insights in development of fungicides with a customer active in the crop protection business. Proof of Concept model: • Parasite: Plasmodium falciparum • Fungal species: Botryotinia fuckeliana and Zymoseptoria tritici • Target – any protein involved Images: CDC/Dr. Mae Melvin (PHIL #2704), 1973 / https://en.wikipedia.org/wiki/Plasmodium_falciparum http://www.agroatlas.ru/en/content/diseases/Olee/Olee_Botrytis_cinerea/ https://commons.wikimedia.org/wiki/File:Septoria-tritici.jpg
  • 14. Strategy to follow • Find out which small molecules interact with Plasmodium falciparum targets − Use database of bioactivity data mined and extracted from literature and patents to get pre- extracted information about proteins from Plasmodium falciparum • Find out which proteins in fungi are homologs to Plasmodium falciparum targets − Build homology maps between fungi and Plasmodium falciparum Image: Elsevier
  • 15. Project overview Database of known targets and active compounds for malaria parasite Map to parasite genes using MedScan (NLP engine) Ortholog mapping to fungal genes using Blastp Candidate compounds affecting fungal targets Parasite gene sequence Fungus gene sequence Biology literature full text
  • 16. Custom dictionary development Pf genes NCBI gene Pf proteins UniProt mapped by GeneID Unique names, synonyms Pf genes with synonyms Functional classes Pf dictionary Mammal, Plant dictionary mapped by MedScan Duplicates • Slowest stage due to manual curation • NCBI gene annotations range from specific to very broad, curation needed to remove ambiguous terms / synonyms • Functional classes – terms corresponding to more that one Pf ID
  • 17. Mapping to fungal genes Aminoacid sequences from RefSeq: best reciprocal hit method based on full- length BLAST alignments Plasmodium falciparum  Yeast  Fungi • Botryotinia fuckeliana – 845 • Zymoseptoria tritici – 866 For more details on the method followed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1160523/
  • 18. Now all the plumbing is ready Database of known targets and active compounds for malaria parasite Map to parasite genes using MedScan (NLP engine) Ortholog mapping to fungal genes using Blastp Candidate compounds affecting fungal targets Parasite gene sequence Fungus gene sequence Biology literature full text
  • 19. Bioactivity data in Reaxys Medicinal Chemistry >35.2 Million bioactivity data points >6.8 Million compounds with bioactivity >27,000 total targets >65,000 chemical species >133,000 medicinal chemistry patents >370,000 medicinal chemistry articles and others >5,000 drug discovery and pharma journals The database contains This data is sourced from
  • 20. Plasmodium bioassay data target mapping
  • 21. Unique compounds after mapping to fungi ~3500 ~1550 Botryotinia fuckeliana Zymoseptoria tritici
  • 22. Top fungal targets with active compounds A number of compounds were already found to be active against the fungi Target, Botryotinia 6-7 7-8 8-9 9-10 10-11 no data Grand Total Plasmepsin-2 194 376 135 21 15 640 1641 Dihydroorotate dehydrogenase (quinone), mitochondrial 135 66 2 315 1025 L-lactate dehydrogenase 61 7 4 212 Plasmepsin-1 22 35 19 10 38 163 Deoxyuridine 5'-triphosphate nucleotidohydrolase 24 3 10 127 Glutathione S-transferase 80 104 Thioredoxin reductase 1, mitochondrial 8 21 63 Histone deacetylase 1 8 13 6 3 8 46 Adenosylhomocysteinase 1 1 15 29 Histone deacetylase 1 3 10 15 Target, Zymoseptoria 6-7 7-8 8-9 9-10 10-11 no data Grand Total Dihydroorotate dehydrogenase (quinone), mitochondrial 135 66 2 315 1025 Plasmepsin IV 14 12 9 9 1 90 175 Plasmepsin-1 22 35 19 10 38 163 Histone deacetylase 1 8 13 6 3 8 46 orotidine-5'-phosphate decarboxylase 1 1 2 4 38 ATPase, Ca++ Transporting, Plasma Membrane 1 9 2 16 Histone deacetylase 1 3 10 15 Aminopeptidase N 4 1 1 12 3-Oxoacyl-(Acyl Carrier Protein) Synthase II 11 3-Oxoacyl-(Acyl Carrier Protein) Synthase I 11
  • 23. Conclusions • Successfully able to map Plasmodium targets and active compounds to find already known and new candidate compounds against fungal targets. • Mapping target names from literature to parasite genes is an essential step (but labour intensive step) to reduce the noise. • Once parasite dictionary and mapping is built, the process can be repeated for many different fungi
  • 24. Questions? • Can also be asked later: f.broek@elsevier.com • LinkedIn: https://www.linkedin.com/in/frederik-van-den-broek/ By Malis - https://commons.wikimedia.org/w/index.php?curid=2633354