Mixtures as first class citizens in the realm of informatics

Alex Clark
Alex ClarkFounder of Molecular Materials Informatics, Scientist at Collaborative Drug Discovery
Alex M. Clark
Mixtures
as
fi
rst class citizens in the realm of informatics
alex@collaborativedrug.com
February 2021
Premise
✤ Most mixtures stored as text or
custom table layouts

✤ Value of upgrading to
cheminformatics is well
established...

✤ ... with the right datastructure,
always just one script away from
what you need

✤ If you can represent it, you can
model it
2
Mol
fi
le Mix
fi
le
InChI MInChI
1980's 2020's
Mixfile/MInChI ✤ Format needs to be:

‣ hierarchical

‣ embed structures when possible

‣ include concentration information

‣ tolerate uncertainty

✤ More verbose ELN-friendly form is Mix
fi
le

✤ Concise form with canonical components is
MInChI (mixtures InChI)
MInChI=0.00.1S/C4H8O/c1-2-4-5-3-1/h1-4H2&C6H12/
c1-6-4-2-3-5-6/h6H,2-5H2,1H3&C6H14/c1-3-5-6-4-2/
h3-6H2,1-2H3&C6H14/c1-4-5-6(2)3/h6H,4-5H2,1-3H3&C6H14/
c1-4-6(3)5-2/h6H,4-5H2,1-3H3&C6H14N.Li/c1-5(2)7-6(3)4;/
h5-6H,1-4H3;/q-1;+1/n{6&{1&{3&2&4&5}}}/
g{1mr0&{1vp0&{5:7pp1&1:2pp1&1:5pp0&1:5pp0}7vp0}}
3
(JSON-serialised)
Data Creation
4
github.com/cdd/mixtures collaborativedrug.com
Formulation Example
✤ Many consumer products are well described
from a chemical perspective

✤ Some components are more easily de
fi
ned
than others

✤ When structure is not available, can use
external identi
fi
ers

✤ Hierarchy encodes information about the
design of the product

✤ Concentrations can be expressed with
uncertainties
5
Comparisons with Structures
InChI=1S/C7H6O3/c8-6-4-2-1-3-5(6)7(9)10/h1-4,8H,(H,9,10)
≡ substructure of
n n
MW 300-500 MW 400-700
≅
Y1.2Ba0.8CuO4 ≅ YBa2Cu3O7−δ
≅
6
Search Queries
>40%
has
has INCI: COCAMIDE DEA
has not substructure
✤ Looking for a certain subset of
external cleaning surfactants,
phosphate-free
7
Informatics Example
✤ Solubility of theophylline

✤ Often delivered in liquid form with mixed solvents: optimising
proportion of drug is important

✤ Consider a scenario where:

‣ all data was provided in Mixtures InChI form

‣ these data exist in openly available repositories

✤ Query:

‣ check that theophylline is present and has concentration

‣ check that other ingredients are solvents

✤ Consider 4 papers with relevant solubility, published over 20 years...
theophylline

nasal anti-in
fl
ammatory
8
https://tinyurl.com/


y3svytfp


➫ 4:13:00
Papers (x4)
9
n n n n
All Together for QSAR
Solubility
0.699 1
15.19 1
1.04 1
3.142 1
0.784 1
0.91 1
6.3 1
13.7 1
11.6 1
13.58 1
6.73 1
9.3 1
8.20 0.8 0.2
16.38 0.5 0.5
13.60 0.2 0.8
(+8 more similar)
15.39 0.333 0.667
26.6 0.5 0.5
17.97 0.083 0.584 0.333
19.06 0.708 0.292
22.59 0.417 0.25 0.333
26.52 0.283 0.25 0.3 0.167
(+14 more similar)
n
10
Deep Eutectics / Carbon Capture
✤ Mixtures of ionic & neutral solvents can
absorb gases like CO2
11
DOI: 10.1021/ef5028873
✤ Want to model?

‣
fi
nding data in literature is hard

‣ curating is extremely laborious

✤ Each datapoint is a mixture...
Mixturfication
✤ Data entry easier as
tabular content

✤ Mixture hierarchy is
implicit
12
Mixtures
✤ Convert each row into a self-contained Mix
fi
le...

✤ ... have solubility of CO2 and SO2 in various solvent combinations

✤ Could be looked up in a database of mixtures from many di
ff
erent sources
13
Free Wilson-esque
✤ Tabulate components as column headings, with proportions - scriptable

✤ Build a basic regression model (PLS)...
14
Absorption
R² = 0.9523
0
0.2
0.4
0.6
0.8
1
1.2
1.4
0 0.2 0.4 0.6 0.8 1 1.2 1.4
Predicted
Measured
Gas Absorption
Cross-populate
✤ Empty cells set to max(Tanimoto ECFP4 × concentration)
15
Absorption
R² = 0.9412
0
0.2
0.4
0.6
0.8
1
1.2
1.4
0 0.2 0.4 0.6 0.8 1 1.2 1.4
Predicted
Measured
Gas Absorption
10-most Significant Descriptors
16
R² = 0.7723
0
0.2
0.4
0.6
0.8
1
1.2
1.4
0 0.2 0.4 0.6 0.8 1 1.2 1.4
Predicted
Measured
Gas Absorption
Labelling Caveat
✤ Mixture data not quite free of implicit assumptions...
17
saturated
single

phase,

liquid
✤ Need additional metadata, e.g.

‣ ontologies

‣ IUPAC terminology

✤ Work in progress
Summary
✤ Open protocols, tools & example data available for representing mixtures

✤ New work
fl
ows become practical with cheminformaticisation of mixtures

✤ Much work to be done to catch up with structure databases

✤ Community building is key

✤ Many industries: lab chemistry, drug formulations, consumer products,
agriculture, analytical standards, safety...
18
Questions?
✤ Contact:

Alex M. Clark alex@collaborativedrug.com (Collaborative Drug Discovery)
19
Journal of Cheminformatics (2019
)

10.1186/s13321-019-0357-4
Open Sourc
e

github.com/cdd/mixtures
CDD Vaul
t

collaborativedrug.com
✤ Also: Leah McEwen (Cornell, InChI, IUPAC)
1 of 19

Recommended

Eurocities presentation on open data by
Eurocities presentation on open dataEurocities presentation on open data
Eurocities presentation on open dataejilgun
248 views12 slides
Mixtures QSAR: modelling collections of chemicals by
Mixtures QSAR: modelling collections of chemicalsMixtures QSAR: modelling collections of chemicals
Mixtures QSAR: modelling collections of chemicalsAlex Clark
259 views24 slides
Mixtures InChI: a story of how standards drive upstream products by
Mixtures InChI: a story of how standards drive upstream productsMixtures InChI: a story of how standards drive upstream products
Mixtures InChI: a story of how standards drive upstream productsAlex Clark
600 views19 slides
Mixtures: informatics for formulations and consumer products by
Mixtures: informatics for formulations and consumer productsMixtures: informatics for formulations and consumer products
Mixtures: informatics for formulations and consumer productsAlex Clark
125 views27 slides
Coordination InChI (2019) by
Coordination InChI (2019)Coordination InChI (2019)
Coordination InChI (2019)Alex Clark
223 views15 slides
Chemical mixtures: File format, open source tools, example data, and mixtures... by
Chemical mixtures: File format, open source tools, example data, and mixtures...Chemical mixtures: File format, open source tools, example data, and mixtures...
Chemical mixtures: File format, open source tools, example data, and mixtures...Alex Clark
777 views20 slides

More Related Content

More from Alex Clark

Autonomous model building with a preponderance of well annotated assay protocols by
Autonomous model building with a preponderance of well annotated assay protocolsAutonomous model building with a preponderance of well annotated assay protocols
Autonomous model building with a preponderance of well annotated assay protocolsAlex Clark
595 views33 slides
Representing molecules with minimalism: A solution to the entropy of informatics by
Representing molecules with minimalism: A solution to the entropy of informaticsRepresenting molecules with minimalism: A solution to the entropy of informatics
Representing molecules with minimalism: A solution to the entropy of informaticsAlex Clark
614 views27 slides
CDD BioAssay Express: Expanding the target dimension: How to visualize a lot ... by
CDD BioAssay Express: Expanding the target dimension: How to visualize a lot ...CDD BioAssay Express: Expanding the target dimension: How to visualize a lot ...
CDD BioAssay Express: Expanding the target dimension: How to visualize a lot ...Alex Clark
833 views37 slides
BioAssay Express by
BioAssay ExpressBioAssay Express
BioAssay ExpressAlex Clark
782 views18 slides
SLAS2016: Why have one model when you could have thousands? by
SLAS2016: Why have one model when you could have thousands?SLAS2016: Why have one model when you could have thousands?
SLAS2016: Why have one model when you could have thousands?Alex Clark
749 views24 slides
The anatomy of a chemical reaction: Dissection by machine learning algorithms by
The anatomy of a chemical reaction: Dissection by machine learning algorithmsThe anatomy of a chemical reaction: Dissection by machine learning algorithms
The anatomy of a chemical reaction: Dissection by machine learning algorithmsAlex Clark
1.3K views18 slides

More from Alex Clark(20)

Autonomous model building with a preponderance of well annotated assay protocols by Alex Clark
Autonomous model building with a preponderance of well annotated assay protocolsAutonomous model building with a preponderance of well annotated assay protocols
Autonomous model building with a preponderance of well annotated assay protocols
Alex Clark595 views
Representing molecules with minimalism: A solution to the entropy of informatics by Alex Clark
Representing molecules with minimalism: A solution to the entropy of informaticsRepresenting molecules with minimalism: A solution to the entropy of informatics
Representing molecules with minimalism: A solution to the entropy of informatics
Alex Clark614 views
CDD BioAssay Express: Expanding the target dimension: How to visualize a lot ... by Alex Clark
CDD BioAssay Express: Expanding the target dimension: How to visualize a lot ...CDD BioAssay Express: Expanding the target dimension: How to visualize a lot ...
CDD BioAssay Express: Expanding the target dimension: How to visualize a lot ...
Alex Clark833 views
BioAssay Express by Alex Clark
BioAssay ExpressBioAssay Express
BioAssay Express
Alex Clark782 views
SLAS2016: Why have one model when you could have thousands? by Alex Clark
SLAS2016: Why have one model when you could have thousands?SLAS2016: Why have one model when you could have thousands?
SLAS2016: Why have one model when you could have thousands?
Alex Clark749 views
The anatomy of a chemical reaction: Dissection by machine learning algorithms by Alex Clark
The anatomy of a chemical reaction: Dissection by machine learning algorithmsThe anatomy of a chemical reaction: Dissection by machine learning algorithms
The anatomy of a chemical reaction: Dissection by machine learning algorithms
Alex Clark1.3K views
Compact models for compact devices: Visualisation of SAR using mobile apps by Alex Clark
Compact models for compact devices: Visualisation of SAR using mobile appsCompact models for compact devices: Visualisation of SAR using mobile apps
Compact models for compact devices: Visualisation of SAR using mobile apps
Alex Clark1.3K views
Green chemistry in chemical reactions: informatics by design by Alex Clark
Green chemistry in chemical reactions: informatics by designGreen chemistry in chemical reactions: informatics by design
Green chemistry in chemical reactions: informatics by design
Alex Clark2.6K views
ICCE 2014: The Green Lab Notebook by Alex Clark
ICCE 2014: The Green Lab NotebookICCE 2014: The Green Lab Notebook
ICCE 2014: The Green Lab Notebook
Alex Clark1.1K views
Cloud hosted APIs for cheminformatics on mobile devices (ACS Dallas 2014) by Alex Clark
Cloud hosted APIs for cheminformatics on mobile devices (ACS Dallas 2014)Cloud hosted APIs for cheminformatics on mobile devices (ACS Dallas 2014)
Cloud hosted APIs for cheminformatics on mobile devices (ACS Dallas 2014)
Alex Clark914 views
Building a mobile reaction lab notebook (ACS Dallas 2014) by Alex Clark
Building a mobile reaction lab notebook (ACS Dallas 2014)Building a mobile reaction lab notebook (ACS Dallas 2014)
Building a mobile reaction lab notebook (ACS Dallas 2014)
Alex Clark1.4K views
Reaction Lab Notebooks for Mobile Devices - Alex M. Clark - GDCh 2013 by Alex Clark
Reaction Lab Notebooks for Mobile Devices - Alex M. Clark - GDCh 2013Reaction Lab Notebooks for Mobile Devices - Alex M. Clark - GDCh 2013
Reaction Lab Notebooks for Mobile Devices - Alex M. Clark - GDCh 2013
Alex Clark1.8K views
Alex Clark : NETTAB 2013 by Alex Clark
Alex Clark : NETTAB 2013Alex Clark : NETTAB 2013
Alex Clark : NETTAB 2013
Alex Clark1.3K views
Open Drug Discovery Teams @ Hacking Health Montreal by Alex Clark
Open Drug Discovery Teams @ Hacking Health MontrealOpen Drug Discovery Teams @ Hacking Health Montreal
Open Drug Discovery Teams @ Hacking Health Montreal
Alex Clark932 views
Pistoia Alliance App Strategy by Alex Clark
Pistoia Alliance App StrategyPistoia Alliance App Strategy
Pistoia Alliance App Strategy
Alex Clark1.1K views
Mobile+Cloud: a viable replacement for desktop cheminformatics? by Alex Clark
Mobile+Cloud: a viable replacement for desktop cheminformatics?Mobile+Cloud: a viable replacement for desktop cheminformatics?
Mobile+Cloud: a viable replacement for desktop cheminformatics?
Alex Clark891 views
Practical cheminformatics workflows with mobile apps by Alex Clark
Practical cheminformatics workflows with mobile appsPractical cheminformatics workflows with mobile apps
Practical cheminformatics workflows with mobile apps
Alex Clark833 views
Alex M. Clark, CINF, ACS 2012 Philadelphia by Alex Clark
Alex M. Clark, CINF, ACS 2012 PhiladelphiaAlex M. Clark, CINF, ACS 2012 Philadelphia
Alex M. Clark, CINF, ACS 2012 Philadelphia
Alex Clark2.1K views
Alex M. Clark, Chemical Education, ACS 2012 Philadelphia by Alex Clark
Alex M. Clark, Chemical Education, ACS 2012 PhiladelphiaAlex M. Clark, Chemical Education, ACS 2012 Philadelphia
Alex M. Clark, Chemical Education, ACS 2012 Philadelphia
Alex Clark1.7K views
Building a mobile app ecosystem for chemistry collaboration by Alex Clark
Building a mobile app ecosystem for chemistry collaborationBuilding a mobile app ecosystem for chemistry collaboration
Building a mobile app ecosystem for chemistry collaboration
Alex Clark507 views

Recently uploaded

Experimental animal Guinea pigs.pptx by
Experimental animal Guinea pigs.pptxExperimental animal Guinea pigs.pptx
Experimental animal Guinea pigs.pptxMansee Arya
28 views16 slides
plasmids by
plasmidsplasmids
plasmidsscribddarkened352
12 views2 slides
Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe... by
Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe...Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe...
Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe...Anmol Vishnu Gupta
26 views12 slides
1978 NASA News Release Log by
1978 NASA News Release Log1978 NASA News Release Log
1978 NASA News Release Logpurrterminator
11 views146 slides
POSTER IV LAWCN_ROVER_IUE.pdf by
POSTER IV LAWCN_ROVER_IUE.pdfPOSTER IV LAWCN_ROVER_IUE.pdf
POSTER IV LAWCN_ROVER_IUE.pdfSOCIEDAD JULIO GARAVITO
11 views1 slide
A giant thin stellar stream in the Coma Galaxy Cluster by
A giant thin stellar stream in the Coma Galaxy ClusterA giant thin stellar stream in the Coma Galaxy Cluster
A giant thin stellar stream in the Coma Galaxy ClusterSérgio Sacani
16 views14 slides

Recently uploaded(20)

Experimental animal Guinea pigs.pptx by Mansee Arya
Experimental animal Guinea pigs.pptxExperimental animal Guinea pigs.pptx
Experimental animal Guinea pigs.pptx
Mansee Arya28 views
Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe... by Anmol Vishnu Gupta
Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe...Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe...
Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe...
A giant thin stellar stream in the Coma Galaxy Cluster by Sérgio Sacani
A giant thin stellar stream in the Coma Galaxy ClusterA giant thin stellar stream in the Coma Galaxy Cluster
A giant thin stellar stream in the Coma Galaxy Cluster
Sérgio Sacani16 views
MODULE-9-Biotechnology, Genetically Modified Organisms, and Gene Therapy.pdf by KerryNuez1
MODULE-9-Biotechnology, Genetically Modified Organisms, and Gene Therapy.pdfMODULE-9-Biotechnology, Genetically Modified Organisms, and Gene Therapy.pdf
MODULE-9-Biotechnology, Genetically Modified Organisms, and Gene Therapy.pdf
KerryNuez126 views
application of genetic engineering 2.pptx by SankSurezz
application of genetic engineering 2.pptxapplication of genetic engineering 2.pptx
application of genetic engineering 2.pptx
SankSurezz12 views
How to be(come) a successful PhD student by Tom Mens
How to be(come) a successful PhD studentHow to be(come) a successful PhD student
How to be(come) a successful PhD student
Tom Mens513 views
Nitrosamine & NDSRI.pptx by NileshBonde4
Nitrosamine & NDSRI.pptxNitrosamine & NDSRI.pptx
Nitrosamine & NDSRI.pptx
NileshBonde418 views
PRINCIPLES-OF ASSESSMENT by rbalmagro
PRINCIPLES-OF ASSESSMENTPRINCIPLES-OF ASSESSMENT
PRINCIPLES-OF ASSESSMENT
rbalmagro12 views
Pollination By Nagapradheesh.M.pptx by MNAGAPRADHEESH
Pollination By Nagapradheesh.M.pptxPollination By Nagapradheesh.M.pptx
Pollination By Nagapradheesh.M.pptx
MNAGAPRADHEESH17 views
Synthesis and Characterization of Magnetite-Magnesium Sulphate-Sodium Dodecyl... by GIFT KIISI NKIN
Synthesis and Characterization of Magnetite-Magnesium Sulphate-Sodium Dodecyl...Synthesis and Characterization of Magnetite-Magnesium Sulphate-Sodium Dodecyl...
Synthesis and Characterization of Magnetite-Magnesium Sulphate-Sodium Dodecyl...
GIFT KIISI NKIN28 views
CSF -SHEEBA.D presentation.pptx by SheebaD7
CSF -SHEEBA.D presentation.pptxCSF -SHEEBA.D presentation.pptx
CSF -SHEEBA.D presentation.pptx
SheebaD714 views

Mixtures as first class citizens in the realm of informatics

  • 1. Alex M. Clark Mixtures as fi rst class citizens in the realm of informatics alex@collaborativedrug.com February 2021
  • 2. Premise ✤ Most mixtures stored as text or custom table layouts ✤ Value of upgrading to cheminformatics is well established... ✤ ... with the right datastructure, always just one script away from what you need ✤ If you can represent it, you can model it 2 Mol fi le Mix fi le InChI MInChI 1980's 2020's
  • 3. Mixfile/MInChI ✤ Format needs to be: ‣ hierarchical ‣ embed structures when possible ‣ include concentration information ‣ tolerate uncertainty ✤ More verbose ELN-friendly form is Mix fi le ✤ Concise form with canonical components is MInChI (mixtures InChI) MInChI=0.00.1S/C4H8O/c1-2-4-5-3-1/h1-4H2&C6H12/ c1-6-4-2-3-5-6/h6H,2-5H2,1H3&C6H14/c1-3-5-6-4-2/ h3-6H2,1-2H3&C6H14/c1-4-5-6(2)3/h6H,4-5H2,1-3H3&C6H14/ c1-4-6(3)5-2/h6H,4-5H2,1-3H3&C6H14N.Li/c1-5(2)7-6(3)4;/ h5-6H,1-4H3;/q-1;+1/n{6&{1&{3&2&4&5}}}/ g{1mr0&{1vp0&{5:7pp1&1:2pp1&1:5pp0&1:5pp0}7vp0}} 3 (JSON-serialised)
  • 5. Formulation Example ✤ Many consumer products are well described from a chemical perspective ✤ Some components are more easily de fi ned than others ✤ When structure is not available, can use external identi fi ers ✤ Hierarchy encodes information about the design of the product ✤ Concentrations can be expressed with uncertainties 5
  • 6. Comparisons with Structures InChI=1S/C7H6O3/c8-6-4-2-1-3-5(6)7(9)10/h1-4,8H,(H,9,10) ≡ substructure of n n MW 300-500 MW 400-700 ≅ Y1.2Ba0.8CuO4 ≅ YBa2Cu3O7−δ ≅ 6
  • 7. Search Queries >40% has has INCI: COCAMIDE DEA has not substructure ✤ Looking for a certain subset of external cleaning surfactants, phosphate-free 7
  • 8. Informatics Example ✤ Solubility of theophylline ✤ Often delivered in liquid form with mixed solvents: optimising proportion of drug is important ✤ Consider a scenario where: ‣ all data was provided in Mixtures InChI form ‣ these data exist in openly available repositories ✤ Query: ‣ check that theophylline is present and has concentration ‣ check that other ingredients are solvents ✤ Consider 4 papers with relevant solubility, published over 20 years... theophylline nasal anti-in fl ammatory 8 https://tinyurl.com/ y3svytfp ➫ 4:13:00
  • 10. All Together for QSAR Solubility 0.699 1 15.19 1 1.04 1 3.142 1 0.784 1 0.91 1 6.3 1 13.7 1 11.6 1 13.58 1 6.73 1 9.3 1 8.20 0.8 0.2 16.38 0.5 0.5 13.60 0.2 0.8 (+8 more similar) 15.39 0.333 0.667 26.6 0.5 0.5 17.97 0.083 0.584 0.333 19.06 0.708 0.292 22.59 0.417 0.25 0.333 26.52 0.283 0.25 0.3 0.167 (+14 more similar) n 10
  • 11. Deep Eutectics / Carbon Capture ✤ Mixtures of ionic & neutral solvents can absorb gases like CO2 11 DOI: 10.1021/ef5028873 ✤ Want to model? ‣ fi nding data in literature is hard ‣ curating is extremely laborious ✤ Each datapoint is a mixture...
  • 12. Mixturfication ✤ Data entry easier as tabular content ✤ Mixture hierarchy is implicit 12
  • 13. Mixtures ✤ Convert each row into a self-contained Mix fi le... ✤ ... have solubility of CO2 and SO2 in various solvent combinations ✤ Could be looked up in a database of mixtures from many di ff erent sources 13
  • 14. Free Wilson-esque ✤ Tabulate components as column headings, with proportions - scriptable ✤ Build a basic regression model (PLS)... 14 Absorption R² = 0.9523 0 0.2 0.4 0.6 0.8 1 1.2 1.4 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Predicted Measured Gas Absorption
  • 15. Cross-populate ✤ Empty cells set to max(Tanimoto ECFP4 × concentration) 15 Absorption R² = 0.9412 0 0.2 0.4 0.6 0.8 1 1.2 1.4 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Predicted Measured Gas Absorption
  • 16. 10-most Significant Descriptors 16 R² = 0.7723 0 0.2 0.4 0.6 0.8 1 1.2 1.4 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Predicted Measured Gas Absorption
  • 17. Labelling Caveat ✤ Mixture data not quite free of implicit assumptions... 17 saturated single phase, liquid ✤ Need additional metadata, e.g. ‣ ontologies ‣ IUPAC terminology ✤ Work in progress
  • 18. Summary ✤ Open protocols, tools & example data available for representing mixtures ✤ New work fl ows become practical with cheminformaticisation of mixtures ✤ Much work to be done to catch up with structure databases ✤ Community building is key ✤ Many industries: lab chemistry, drug formulations, consumer products, agriculture, analytical standards, safety... 18
  • 19. Questions? ✤ Contact: Alex M. Clark alex@collaborativedrug.com (Collaborative Drug Discovery) 19 Journal of Cheminformatics (2019 ) 10.1186/s13321-019-0357-4 Open Sourc e github.com/cdd/mixtures CDD Vaul t collaborativedrug.com ✤ Also: Leah McEwen (Cornell, InChI, IUPAC)