xtalPIMS - A tool for managing your crystallization experiments

Dr Ian Berryian.berry@evotec.com

Evotec (UK) LtdFormally:

BIOXHIT Working Group 1 Coordinator & Software Developer at OPPF, Oxford

Overview

• What is xtalPIMS?• Where does it fit?• Developers & Usage• Interfaces & Integrations• What is available…• …and what is not…• The Future

What is xtalPiMS?

• An extension to PiMS to cover crystallization, crystal handling and data collection that will:– Provide screen management– Integrate with automatic and manual imaging

systems– Integrate with liquid handling robots– Provide a single interface for viewing images from

multiple imagers– Provide a Trip Management System to integrate

with synchrotrons and home sources

MachineIntegration

MachineIntegration

Deposition(PDB)

Synchrotron(ISPyB)

ProteinProduction

(PiMS)Machine

Integration

Where does it fit?

Crystallization(xtalPiMS)

DataManagement

(Xtrack) & DataProcessing

(CCP4)

Developers and usage

• BIOXHIT funded three developers: – Ian Berry (OPPF, UK) (until June 2008)– Gael Seroul (EMBL Grenoble, France) (until Sept

2009)– Diederick de Vries (NKI, The Netherlands) (until

Feb 2008)• Current version in full time use at the OPPF

(20,000 plates, 50,000,000 images)

Interfaces & Integrations

• Liquid Handling robot integration• Imaging System integration• Image processing / analysis integration• Web-based viewing interface

– Experiment Management– Screen Management– Optimisation Management– Trip Management (merging with e-HTPX)– Data Collection results

Experiment Management

• Users should be able to plan, order and carry out crystallization experiments through xtalPIMS

• Users should be able to monitor the progress of their experiments

• Users should be able to make decisions based on the information that is available, e.g. create an optimization experiment from one or more hit, request that the hit is tested in-house or at a synchrotron

Screen & Optimization Management

• xtalPIMS will aim to provide tools for:– Managing initial sparse-matrix screens

• Manufacturer screens• In-house “blocks”• Optimized screens for particular protein

type– Managing optimizations from a crystal hit

using a variety of algorithms, e.g.:• Standard patterns, e.g. OPPF optimization

strategy• Gradients• Hand crafted screens

– Management of stock solutions, deep well blocks, etc.

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Block 1 Block 2 Block 3 Block 4 Block 5 Index JCSG Limited Protein Limited Protein2

Extra-Cellular Intra-Cellular Eukaryotic Prokaryotic Viral Eukaryotic Viral Prokaryotic Deglycoselated Glycoselated

Liquid Handling Robotics• With the ability to create

experiments and manage screens, xtalPIMS should be able to interact with liquid handling robots by providing compatible control files to make the process of creating the crystallization plates as simple as possible

• Feedback from liquid handling robotics can be used as a means of tracking what has been done

Imaging System Integration

• Quite often the software from imaging systems only works for their single hardware platform

• xtalPIMS is designed to be hardware agnostic, and we aim to integrate images produced by any crystal imaging system (even microscopes)

• There are three levels of integration:– Simple – no interaction with the hardware– Intermediate – some interaction with

hardware– Full – the hardware and control software send

images to xtalPIMS

Image processing / analysis• Once taken, images will be able to be

processed to detect crystals or other interesting features

• Currently uses ALICE (Automated anaLysis of Images from Crystallization Experiments) developed by Julie Wilson at York Structural Biology Laboratory

Trip Management

• For a scientist it provides a management tool for:– Lab hardware (pins, pucks, dewars, etc)– Crystal handling (e.g. soak experiments)– Mounting crystals– Testing on in-house sources– Shipments to synchrotrons– Return shipments – Beamline meta-data retrieval

Trip Management Process

• Users select crystals or projects to be put forward for a data collection

• Summary generated for trip management committee• Crystals / projects either approved, delayed for a

later trip or rejected• Crystal details made available in the crystal mounting

interface• Crystals and crystal details sent automatically

through to synchrotron or home-source so data is available at those sites

Data Collection Data

• Retrieve data from Synchrotron data store (e.g. ISPyB) and store in PIMS db, with links to frames on local file store

• Data processing with XIA2 Portal• Further integration with CCP4 -

Links to run CCP4 programs on local clusters / store results in PIMS DB / etc...

What is available…

• Image Viewer• Image analysis for Formulatrix Robotics• Simple experiment monitoring• eHTPX preparation for a synchrotron trip• eHTPX return of data into XTrack

… and what is not (yet!)

• Liquid handling integration• Wider imager integration• Screen & Optimization management• Experiment creation• Return information from ISPyB • Links to the PIMS database

The future...

• There has been a lot of interest in xtalPIMS…• Robotics companies are happy to work with

us…• Labs are happy to work with us to get it

working in their labs…• We are currently investigating ways of funding

future development.

Acknowledgements• BIOXHIT• OPPF

– Robert Esnouf– Jon Diprose– Dave Stuart

• NKI– Tassos Perrakis– Diederick de Vries (xtalPiMS developer)

• EMBL Grenoble– Josan Marquez– Gael Seroul (xtalPiMS developer)

• All the PiMS developers• All the e-HTPX developers• Evotec

Tomorrow's Drugs Today™

Contact John Barker (john.barker@evotec.com)http://www.evotec.com

• High throughput protein production and crystallization facility

• Experienced team members with previous industrial experience gained with Vertex, Astex, Pantherix and British Biotech

• Range of target class expertise– Aspartyl & Serine Protease – Kinase– Metalloenzymes– Miscellaneous Antibacterial Targets – NHR– Other enzymes – ATPase,

dehydrogenase, synthase, transhydrogenase

– Phosphatases

PDF

CK2

PTP1b

Hsp90

p38

More information• PiMS

– http://www.pims-lims.org• xtalPiMS

– http://www.oppf.ox.ac.uk/xtalpims• e-HTPX

– http://www.oppf.ac.uk/ehtpx

Hands on demo this afternoon…

Thank you for listening

Demo

Demo

Demo

Demo

Demo

Demo