Lhasa trusted community KNIME nodes Data processing and metabolism prediction

Dr Samuel Webb samuelwebblhasalimitedorg

Who am I

bull Working within the Research Group at Lhasa Limited

bull Activities include bull Software tool development bull Data mining bull Algorithm development bull Managing Lhasarsquos internal KNIME nodes and build bull Managing Lhasarsquos open source KNIME contribution

What is KNIME

bull Analytics platform

bull Core software open source

bull Software development kit (SDK) makes it easy to develop your own nodes

ldquoOur KNIME Analytics Platform is the leading open solution for data-driven innovation designed for discovering the potential hidden in data mining for fresh insights or predicting new futures Organizations can take their collaboration productivity and performance to the next level with a robust range of commercial extensions to our open source platformrdquo ndash wwwknimeorgabout

Who am I

bull Working within the Research Group at Lhasa Limited

bull Activities include bull Software tool development bull Data mining bull Algorithm development bull Managing Lhasarsquos internal KNIME nodes and build bull Managing Lhasarsquos open source KNIME contribution

What is KNIME

bull Analytics platform

bull Core software open source

bull Software development kit (SDK) makes it easy to develop your own nodes

ldquoOur KNIME Analytics Platform is the leading open solution for data-driven innovation designed for discovering the potential hidden in data mining for fresh insights or predicting new futures Organizations can take their collaboration productivity and performance to the next level with a robust range of commercial extensions to our open source platformrdquo ndash wwwknimeorgabout

What is KNIME

bull Analytics platform

bull Core software open source

bull Software development kit (SDK) makes it easy to develop your own nodes

ldquoOur KNIME Analytics Platform is the leading open solution for data-driven innovation designed for discovering the potential hidden in data mining for fresh insights or predicting new futures Organizations can take their collaboration productivity and performance to the next level with a robust range of commercial extensions to our open source platformrdquo ndash wwwknimeorgabout

KNIME and cheminformatics

bull Large number of downloads for the community plugins

bull Large number of community developers

bull Some examples of node types

bull Chemical engines ChemAxon RDKit CDK and Indigo bull General purpose and algorithms Vernalis Enalos and Lhasa bull Data searches CIR and EMBL-EBI

What does Lhasa use KNIME for

bull Data processing bull Combining datasets find overlap compare activities when

overlap exists join in data where no overlap existshellip bull Monitoring

bull Extracting data from a the database which has been altered identifying review work content

bull (Q)SAR bull Model building clustering algorithm development

applicability domains chemical space investigationhellip

LHASA CONTRIBUTION TO KNIME

Free open source plugins released

What have we released

General nodes bull Data manipulation

bull Discretise

bull Model scoring

bull Binary Scorer bull Binned performance bull Result

bull Table manipulation

bull Dumb Joiner (to be deprecated) bull Row Splitter (col+) bull Table to HTML

Metabolism nodes bull SMARTCyp 242

bull Cytochrome P450 site of metabolism predictor

bull Integration of Patrick Rydbergrsquos open source tool

bull WhichCyp 12

bull Prediction of binding to Cytochrome P450 isoform(s)

bull Integration of Patrick Rydbergrsquos open source tool

Disclaimer

bull These nodes plugins are not Lhasa Limited products

bull Help support for these nodes is provided via bull The KNIME forum httpstechknimeorgforumlhasa-nodes bull knimelhasalimitedorg (preferable to use the KNIME

forum)

What does Lhasa use KNIME for

bull Data processing bull Combining datasets find overlap compare activities when

overlap exists join in data where no overlap existshellip bull Monitoring

bull Extracting data from a the database which has been altered identifying review work content

bull (Q)SAR bull Model building clustering algorithm development

applicability domains chemical space investigationhellip

LHASA CONTRIBUTION TO KNIME

Free open source plugins released

What have we released

General nodes bull Data manipulation

bull Discretise

bull Model scoring

bull Binary Scorer bull Binned performance bull Result

bull Table manipulation

bull Dumb Joiner (to be deprecated) bull Row Splitter (col+) bull Table to HTML

Metabolism nodes bull SMARTCyp 242

bull Cytochrome P450 site of metabolism predictor

bull Integration of Patrick Rydbergrsquos open source tool

bull WhichCyp 12

bull Prediction of binding to Cytochrome P450 isoform(s)

bull Integration of Patrick Rydbergrsquos open source tool

Disclaimer

bull These nodes plugins are not Lhasa Limited products

bull Help support for these nodes is provided via bull The KNIME forum httpstechknimeorgforumlhasa-nodes bull knimelhasalimitedorg (preferable to use the KNIME

forum)

LHASA CONTRIBUTION TO KNIME

Free open source plugins released

What have we released

General nodes bull Data manipulation

bull Discretise

bull Model scoring

bull Binary Scorer bull Binned performance bull Result

bull Table manipulation

bull Dumb Joiner (to be deprecated) bull Row Splitter (col+) bull Table to HTML

Metabolism nodes bull SMARTCyp 242

bull Cytochrome P450 site of metabolism predictor

bull Integration of Patrick Rydbergrsquos open source tool

bull WhichCyp 12

bull Prediction of binding to Cytochrome P450 isoform(s)

bull Integration of Patrick Rydbergrsquos open source tool

Disclaimer

bull These nodes plugins are not Lhasa Limited products

bull Help support for these nodes is provided via bull The KNIME forum httpstechknimeorgforumlhasa-nodes bull knimelhasalimitedorg (preferable to use the KNIME

forum)

What have we released

General nodes bull Data manipulation

bull Discretise

bull Model scoring

bull Binary Scorer bull Binned performance bull Result

bull Table manipulation

bull Dumb Joiner (to be deprecated) bull Row Splitter (col+) bull Table to HTML

Metabolism nodes bull SMARTCyp 242

bull Cytochrome P450 site of metabolism predictor

bull Integration of Patrick Rydbergrsquos open source tool

bull WhichCyp 12

bull Prediction of binding to Cytochrome P450 isoform(s)

bull Integration of Patrick Rydbergrsquos open source tool

Disclaimer

bull These nodes plugins are not Lhasa Limited products

bull Help support for these nodes is provided via bull The KNIME forum httpstechknimeorgforumlhasa-nodes bull knimelhasalimitedorg (preferable to use the KNIME

forum)

Disclaimer

bull These nodes plugins are not Lhasa Limited products

bull Help support for these nodes is provided via bull The KNIME forum httpstechknimeorgforumlhasa-nodes bull knimelhasalimitedorg (preferable to use the KNIME

forum)

More information

bull httpstechknimeorglhasa-nodes-for-knime

Why would you use these nodes

Here we calculate the performance of the Random Forest with Morgan

and MACCS fingerprints

Convert the performance table to

HTML and email

Filter out rows where either model predict

active

Why would you use these nodes

Here we calculate the performance of the Random Forest with Morgan

and MACCS fingerprints

Convert the performance table to

HTML and email

Filter out rows where either model predict

active

Generic nodes model performance

bull Similar functionality to the Scorer node

bull Calculates various performance metrics for binary classification models

bull Can choose multiple prediction columns

Generic nodes table to HTML

bull Convert a table to a single HTML cell

bull The String render will render HTML tags

bull Select which columns to include

bull StringValue IntValue DoubleValue

bull Creates a single cell output

SMARTCyp 242

bull SMARTCyp is a method for prediction of which sites in a molecule

that are most liable to metabolism by Cytochrome P450

bull It has been shown to be applicable to metabolism by the isoforms

1A2 2A6 2B6 2C8 2C19 2E1 and 3A4 and specific models for

the isoform 2C9 and isoform 2D6 are included in KNIME 242

bull SMARTCyp is Developed by the Department of Drug Design and

Pharmacology at the University of Copenhagen and is funded by

Lhasa Limited More details can be found at

httpwwwfarmakudksmartcypaboutphp

Why would you use these nodes

Here we calculate the performance of the Random Forest with Morgan

and MACCS fingerprints

Convert the performance table to

HTML and email

Filter out rows where either model predict

active

Generic nodes model performance

bull Similar functionality to the Scorer node

bull Calculates various performance metrics for binary classification models

bull Can choose multiple prediction columns

Generic nodes table to HTML

bull Convert a table to a single HTML cell

bull The String render will render HTML tags

bull Select which columns to include

bull StringValue IntValue DoubleValue

bull Creates a single cell output

SMARTCyp 242

bull SMARTCyp is a method for prediction of which sites in a molecule

that are most liable to metabolism by Cytochrome P450

bull It has been shown to be applicable to metabolism by the isoforms

1A2 2A6 2B6 2C8 2C19 2E1 and 3A4 and specific models for

the isoform 2C9 and isoform 2D6 are included in KNIME 242

bull SMARTCyp is Developed by the Department of Drug Design and

Pharmacology at the University of Copenhagen and is funded by

Lhasa Limited More details can be found at

httpwwwfarmakudksmartcypaboutphp

Generic nodes model performance

bull Similar functionality to the Scorer node

bull Calculates various performance metrics for binary classification models

bull Can choose multiple prediction columns

Generic nodes table to HTML

bull Convert a table to a single HTML cell

bull The String render will render HTML tags

bull Select which columns to include

bull StringValue IntValue DoubleValue

bull Creates a single cell output

SMARTCyp 242

bull SMARTCyp is a method for prediction of which sites in a molecule

that are most liable to metabolism by Cytochrome P450

bull It has been shown to be applicable to metabolism by the isoforms

1A2 2A6 2B6 2C8 2C19 2E1 and 3A4 and specific models for

the isoform 2C9 and isoform 2D6 are included in KNIME 242

bull SMARTCyp is Developed by the Department of Drug Design and

Pharmacology at the University of Copenhagen and is funded by

Lhasa Limited More details can be found at

httpwwwfarmakudksmartcypaboutphp

Generic nodes table to HTML

bull Convert a table to a single HTML cell

bull The String render will render HTML tags

bull Select which columns to include

bull StringValue IntValue DoubleValue

bull Creates a single cell output

SMARTCyp 242

bull SMARTCyp is a method for prediction of which sites in a molecule

that are most liable to metabolism by Cytochrome P450

bull It has been shown to be applicable to metabolism by the isoforms

1A2 2A6 2B6 2C8 2C19 2E1 and 3A4 and specific models for

the isoform 2C9 and isoform 2D6 are included in KNIME 242

bull SMARTCyp is Developed by the Department of Drug Design and

Pharmacology at the University of Copenhagen and is funded by

Lhasa Limited More details can be found at

httpwwwfarmakudksmartcypaboutphp

SMARTCyp 242

bull SMARTCyp is a method for prediction of which sites in a molecule

that are most liable to metabolism by Cytochrome P450

bull It has been shown to be applicable to metabolism by the isoforms

1A2 2A6 2B6 2C8 2C19 2E1 and 3A4 and specific models for

the isoform 2C9 and isoform 2D6 are included in KNIME 242

bull SMARTCyp is Developed by the Department of Drug Design and

Pharmacology at the University of Copenhagen and is funded by

Lhasa Limited More details can be found at

httpwwwfarmakudksmartcypaboutphp

SMARTCyp 242 usage

bull Letrsquos recreate the results table from bull httpwwwncbinlmnihgovpmcarticlesPMC4055970 bull SMARTCyp A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism bull Patrik Rydbergdagger David E Gloriamdagger Jed ZaretzkiDagger Curt BrenemanDagger and Lars Olsendagger

bull Metabolic position = any site listed as primary secondary or tertiary bull Use the top 3 predicted sites Accuracy increases as you increase the rank

limit bull When considering only the top ranked site there is a 65 accuracy in

identifying an experimentally seen SOM vs 81 using the top 3 sites

SMARTCyp 242 usage

SMARTCyp 242 usage

SMARTCyp 242 usage

SMARTCyp 242 usage

SMARTCyp 242 usage

bull Here wersquove incorporated multiple

chemical engines from the same platform

bull RDKit

bull Rendering

bull CDK

bull Rendering bull SMARTCyp processing

WhichCyp

bull Predicts binding to Cyp isoforms 1A2 2C9 2C19 2D6 and 3A4

bull Further reading

bull Michal Rostkowski Ola Spjuth and Patrik Rydberg WhichCyp Prediction of Cytochromes P450 Inhibition Bioinformatics 2013 29 2051-2052

SMARTCyp 242 usage

SMARTCyp 242 usage

SMARTCyp 242 usage

SMARTCyp 242 usage

bull Here wersquove incorporated multiple

chemical engines from the same platform

bull RDKit

bull Rendering

bull CDK

bull Rendering bull SMARTCyp processing

WhichCyp

bull Predicts binding to Cyp isoforms 1A2 2C9 2C19 2D6 and 3A4

bull Further reading

bull Michal Rostkowski Ola Spjuth and Patrik Rydberg WhichCyp Prediction of Cytochromes P450 Inhibition Bioinformatics 2013 29 2051-2052

SMARTCyp 242 usage

SMARTCyp 242 usage

SMARTCyp 242 usage

bull Here wersquove incorporated multiple

chemical engines from the same platform

bull RDKit

bull Rendering

bull CDK

bull Rendering bull SMARTCyp processing

WhichCyp

bull Predicts binding to Cyp isoforms 1A2 2C9 2C19 2D6 and 3A4

bull Further reading

bull Michal Rostkowski Ola Spjuth and Patrik Rydberg WhichCyp Prediction of Cytochromes P450 Inhibition Bioinformatics 2013 29 2051-2052

SMARTCyp 242 usage

SMARTCyp 242 usage

bull Here wersquove incorporated multiple

chemical engines from the same platform

bull RDKit

bull Rendering

bull CDK

bull Rendering bull SMARTCyp processing

WhichCyp

bull Predicts binding to Cyp isoforms 1A2 2C9 2C19 2D6 and 3A4

bull Further reading

bull Michal Rostkowski Ola Spjuth and Patrik Rydberg WhichCyp Prediction of Cytochromes P450 Inhibition Bioinformatics 2013 29 2051-2052

SMARTCyp 242 usage

bull Here wersquove incorporated multiple

chemical engines from the same platform

bull RDKit

bull Rendering

bull CDK

bull Rendering bull SMARTCyp processing

WhichCyp

bull Predicts binding to Cyp isoforms 1A2 2C9 2C19 2D6 and 3A4

bull Further reading

bull Michal Rostkowski Ola Spjuth and Patrik Rydberg WhichCyp Prediction of Cytochromes P450 Inhibition Bioinformatics 2013 29 2051-2052

WhichCyp

bull Predicts binding to Cyp isoforms 1A2 2C9 2C19 2D6 and 3A4

bull Further reading

bull Michal Rostkowski Ola Spjuth and Patrik Rydberg WhichCyp Prediction of Cytochromes P450 Inhibition Bioinformatics 2013 29 2051-2052

WhichCyp usage

bull Renders images of the predictions as a PNG

bull May be updated to SVG in the future

bull Input a structure column that is compatible

with a CDK Value such as

bull Mol bull SDF bull Smiles bull CDK

bull Outputs the values you would get in the CSV

file when running manually

bull Binding Missing Signatures and sensitivity warnings

WHERE CAN I GET THEM

Getting our nodes

bull Download KNIME httpswwwknimeorgdownloadsoverview

bull Selecting + all free extensions and Lhasarsquos will be included

WHERE CAN I GET THEM

Getting our nodes

bull Download KNIME httpswwwknimeorgdownloadsoverview

bull Selecting + all free extensions and Lhasarsquos will be included

Getting our nodes

bull Download KNIME httpswwwknimeorgdownloadsoverview

bull Selecting + all free extensions and Lhasarsquos will be included

Getting our nodes

bull Alternatively they can be added to an existing KNIME

bull Trusted Community Contributions - httpupdateknimeorgcommunity-contributionstrusted31

Thank you

Support httpstechknimeorgforum