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Zawartość zarchiwizowana w dniu 2024-06-18

Enabling the interoperability of cytometric data – a novel bioinformatics approach for revealing systems level understanding of cell cycle dynamics

Final Report Summary - CELLULAR INFORMATICS (Enabling the interoperability of cytometric data - a novel bioinformatics approach for revealing systems level understanding of cell cycle dynamics)

The work programme funded by the Marie Curie International Outgoing Fellowship of the Seventh Framework Programme (FP7-MC-IOF) with Grant Agreement No 254046 - entitled CELLULAR INFORMATICS - has enabled the researcher Dr Imtiaz A Khan to go to the Broad Institute (MIT and Harvard), United States of America (USA) and work with the CellProfiler team at the Imaging Platform (led by Dr Carpenter) to understand how the concepts of cellular informatics can be translated into an open-source tool. The CELLULAR INFORMATICS programme of work consists of seven clear work packages (WPs) which have been undertaken in a methodical and concise manner ensuring that the outcomes for each adequately contribute to the scientific objective of the programme stated; to permit a seamless exchange - in other words, interoperability - between data derived from different cellular analysis technologies ranging from fluid flow systems to advanced imaging - so that such data is within accessible structures for hypothesis testing. By meeting this challenge that truly delivers the visionary concepts of an open-science forum, where the provenance of data and the scientific methodologies used to derive the data become highly accessible and accessible, thus maintaining the scientific value of the original data.

The premise for this work forms the basis that we propose, that it is the lack of suitable tools that imposes the key obstacle for unambiguous annotation and interpretation of experimental protocols and providing a rich context for experiment derived data for discovery. There is a distinct lack of community coherence for capturing 'best cytometric practice' that is able to scale from a low to a high-throughput thus disconnecting the high-content screening strategies from the highly reductionist cell biology approach. Here we propose to develop an open-source tool ProtocolNavigator to enable the cytometry or cell-based assay community to annotate protocols and map spatiotemporal actions of laboratory practice (see http://www.ProtocolNavigator.org(odnośnik otworzy się w nowym oknie) online for further details).

The effective collaboration established between Cardiff University and the Broad Institute has led to the development of ProtocolNavigator a tool with the capacity to operate in a specific context that meets new challenges for data handling, exchange, interrogation and interpretation in cell-based assays; thus meeting the requirements for good laboratory practice. PN (written in Python 2.5) provides a virtual laboratory environment where users recognise and simulate laboratory-based actions and according to these actions, a time-dependent workflow map is automatically drawn, that represents both the design experiment and the underlying practice of the experimentalist. Thus, the overall objective has been to incorporate fundamental principles for data recording, but to break down barriers of complacency and compliance amongst users. Furthermore, the long-term objective has been to project forward and determine the tools required for an open-science forum.

There has been unexpected but welcome outcome of the project that has come about from discussions and presentations within various interdisciplinary consortium at Cardiff and Swansea (funded by the EPSRC, BBSRC); and that is the role of tools such as ProtocolNavigator on the practice and perception within interdisciplinary science. Fundamental research questions include: How easily do experts from different disciplines understand each other's work? What mechanisms in ProtocolNavigator promote knowledge exchange within the group? By asking these fundamental social questions we have been able to develop functionality into ProtocolNavigator that directly embraces technology development issues, visualisation maps for interaction and finally output or exchange concepts. These have been perpetuated and informed by a new collaboration with The ESRC Centre for Economic and Social Aspects of Genomics (Cesagen, CardiffUniversity (Dr N Stephens)). We believe that using this robust approach, for the first time the socio-economic impact of quality control or best practice standards could become apparent and their significance and role better defined. Uptake by industry of standard approaches would propel the motivation and influence the expansion and relevance in cell-based screening and therapy.

The final phase of this project has been to actively engage prospective collaborators and translational partners back in the UK and within the wider international cytometry community. The IOF fellow Dr Imtiaz Khan has been very active in this respect. He has been very successful in inspiring fellow peers in bioinformatics and computational sciences with a view of developing ProtocolNavigator for the future to meet the challenges of interactive open-science discovery environments. At the same time he has been discussing within cytometry forums the uses of the ProtocolNavigator tool bolted onto existing and new data repositories linked to publishing houses. As the same time ProtocolNavigator and its underlying concepts are being reviewed for application areas in tissue banks and for the development of audit trailing and metadata convergence appropriate in the establishment of cell banks and academic laboratories. ProtocolNavigator certainly has a future and a significant role to play in biomolecular imaging and data interoperability, and has been embraced in large interdisciplinary projects, related to stem cell technology development, systems biology and assay quality control.
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