xtal PIMS - A tool for managing your crystallization experiments
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Transcript of xtal PIMS - A tool for managing your crystallization experiments
xtalPIMS - A tool for managing your crystallization experiments
Dr Ian [email protected]
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 ([email protected])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
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