CytometryML

CytometryML is an effort to produce a set of XML schemas to define Cytometry data. This is an open effort, and we appreciate your help.

Ideally, all of the groups and societies, whose work is relevant to Cytometry, should join together to produce one standard. Unfortunately, this may not be possible in the near future. However, these societies and groups should, at least, try to maximize interoperability by using the same data-types.

The data-types in CytometryML have been reused from the Digital Imaging and Communications in Medicine (DICOM) standard, Flow Cytometry Standard (FCS), and other standards. It has been possible, as shown in the CytometryML schemas, to employ the same standard to describe Flow and Image Cytometry. In fact, both a flow cytometer and a digital microscope were derived by restriction from a generic cytometry instrument.

The DICOM hierarchy of patient, study, series, and instance has served as the basis of the overall design of CytometryML. XML schemas that describe the series and instance have been created that have generated XML pages for both flow cytometry and digital microscopy series and instances. These files have been included in this release (Please see below.)

CytometryML XML Pages and Schemas

CytometryML has been united into one group of schemas, which is specific to CytometryML and includes some general utility schemas that can be used for other applications.

Zip file of CytometryML Schemas, as of 26 September, 2010.

Zip file of CytometryML XML Pages, as of  26 September, 2010.

Zip file of CytometryML Projects, as of  26 September, 2010.


Pathology Informatics 2010 Poster

Robert C. Leif and Stephanie H. Leif, Unification of CytometryML, DICOM and Flow Cytometry Standard, Poster from the Annual Pathology Informatics Conference.

CytometryML Papers

Cytometry Standards papers that can be obtained from Wiley-Liss

Robert C. Leif, Toward the integration of cytomics and medicine, J. Biophoton. Special Issue: Towards in vivo Flow Cytometry 2, Pages:482-493

Abstract

The integration of cytomics research and healthcare informatics will facilitate technology transfer and reduce medical costs. The CytometryML prototype of the Advanced Cytometry Standard (ACS) has the benefits of including microscopic image and flow list-mode data, being based on XML and thus is compatible with existing medical and scientific informatics standards, such as HL7, and employing a design based upon the Digital Imaging and Communications in Medicine (DICOM) standard. The reuse of the well tested DICOM model resulted in a great decrease in the design and documentation effort and increased probability of reliability. Schemas for flow cytometers and microscopes have been created. XML schemas for two related types of container (ZIP) files have been specified for a set of measurements. The series and instance containers respectively include the metadata that is constant and the metadata that is specific to an individual or small closely related group of measurements. ( 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)


Josef Spidlen, Robert C. Leif, Wayne Moore, Mario Roederer, International Society for the Advancement of Cytometry Data Standards Task Force, Ryan R. Brinkman, Gating-ML: XML-based gating descriptions in flow cytometry, Cytometry Part A 73A, Issue 12, Date: December 2008, Pages: 1151-1157

Abstract

The lack of software interoperability with respect to gating due to lack of a standardized mechanism for data exchange has traditionally been a bottleneck, preventing reproducibility of flow cytometry (FCM) data analysis and the usage of multiple analytical tools. To facilitate interoperability among FCM data analysis tools, members of the International Society for the Advancement of Cytometry (ISAC) Data Standards Task Force (DSTF) have developed an XML-based mechanism to formally describe gates (Gating-ML). Gating-ML, an open specification for encoding gating, data transformations and compensation, has been adopted by the ISAC DSTF as a Candidate Recommendation. Gating-ML can facilitate exchange of gating descriptions the same way that FCS facilitated for exchange of raw FCM data. Its adoption will open new collaborative opportunities as well as possibilities for advanced analyses and methods development. The ISAC DSTF is satisfied that the standard addresses the requirements for a gating exchange standard. 2008 International Society for Advancement of Cytometry


Jamie A. Lee, Josef Spidlen, Keith Boyce, Jennifer Cai, Nicholas Crosbie, Mark Dalphin, Jeff Furlong, Maura Gasparetto, Michael Goldberg, Elizabeth M. Goralczyk, Bill Hyun, Kirstin Jansen, Tobias Kollmann, Megan Kong, Robert Leif, Shannon McWeeney, Thomas D. Moloshok, Wayne Moore, Garry Nolan, John Nolan, Janko Nikolich-Zugich, David Parrish, Barclay Purcell, Yu Qian, Biruntha Selvaraj, Clayton Smith, Olga Tchuvatkina, Anne Wertheimer, Peter Wilkinson, Christopher Wilson, James Wood, Robert Zigon, The International Society for Advancement of Cytometry Data Standards Task Force, Richard H. Scheuermann, Ryan R. Brinkman, MIFlowCyt: The minimum information about a flow cytometry experiment, Cytometry Part A 73A, Issue 10, Date: October 2008, Pages: 926-930 

Abstract

A fundamental tenet of scientific research is that published results are open to independent validation and refutation. Minimum data standards aid data providers, users, and publishers by providing a specification of what is required to unambiguously interpret experimental findings. Here, we present the Minimum Information about a Flow Cytometry Experiment (MIFlowCyt) standard, stating the minimum information required to report flow cytometry (FCM) experiments. We brought together a cross-disciplinary international collaborative group of bioinformaticians, computational statisticians, software developers, instrument manufacturers, and clinical and basic research scientists to develop the standard. The standard was subsequently vetted by the International Society for Advancement of Cytometry (ISAC) Data Standards Task Force, Standards Committee, membership, and Council. The MIFlowCyt standard includes recommendations about descriptions of the specimens and reagents included in the FCM experiment, the configuration of the instrument used to perform the assays, and the data processing approaches used to interpret the primary output data. MIFlowCyt has been adopted as a standard by ISAC, representing the FCM scientific community including scientists as well as software and hardware manufacturers. Adoption of MIFlowCyt by the scientific and publishing communities will facilitate third-party understanding and reuse of FCM data. 2008 International Society for Advancement of Cytometry


R.C. Leif, S.H. Leif, S.B. Leif, CytometryML, An XML Format based on DICOM for Analytical Cytology Data Cytometry 54A pp. 56-65 (2003).

Abstract

Background: Flow Cytometry Standard (FCS) was initially created to standardize software researchers use to analyze, transmit, and store data produced by flow cytometers and sorters. Because of the clinical utility of flow cytometry, it is necessary to have a standard consistent with the requirements of medical regulatory agencies.

Method:1) Extend the existing mapping of FCS to the Digital Imaging and Communications in Medicine (DICOM) standard to include list-mode data produced by flow, laser scanning cytometry, and microscopic image cytometry. FCS list-mode was mapped to the DICOM Waveform Information Object. 2) Create a collection of XML schemas to express the DICOM analytical cytology text based data-types except for large binary objects. 3) Accomplish this creation of a cytometry markup language, CytometryML, in an open environment that is subject to continuous peer review.

Results:The feasibility of expressing the data contained in FCS, including list-mode in DICOM, has been demonstrated; and a preliminary mapping for list-mode data in the form of XML Schemas and documents has been completed. DICOM permits the creation of indices that can be used to rapidly locate in a list-mode file the cells that are members of a subset. DICOM and its coding schemes for other medical standards can be represented by XML schemas, which can be combined with other relevant XML applications, such as Mathematical Markup Language (MathML).

Conclusions:The use of XML format based on DICOM for analytical cytology has met most of the previously specified requirements and appears capable of meeting the others; therefore, the present FCS should be retired and replaced by an open, XML based standard, CytometryML.


Abstracts of Papers Concerning Cytometry Standards That Can Be Downloaded:

R.C. Leif Safe Software Standards and XML Schemas (preprint) in SPIE Proc. Vol. 7556 (2010).

Abstract

The goal of this work is to develop a safe software construction means for an XML based data standard for a class of medical devices, cytometry instruments. Unfortunately, the amount of empirical evidence to archive this goal is minimal. Therefore, technologies associated with high reliability were employed together with reuse of existing designs.

The basis for a major part of the design was the Digital Imaging and Communications in Medicine (DICOM) standard and the Flow Cytometry Standard (FCS). Since the DICOM Standard is a Class II device, the safety of software should be maximized. The XML Schema Definition Language (XSDL) has been used to develop schemas that maximize readability, modularity, strong typing, and reuse. An instance and an instrument XML schema were created for data obtained with a microscope by importing multiple schemas that each consisted of a class that described one object. This design was checked by validating the schemas and creating XML pages from them.

R.C. Leif An XML Cytometry Standard Based on DICOM (preprint) in SPIE Proc. Vol. 7264 (2009).

Abstract

Introduction: The International Society for the Advancement of Cytometry (ISAC) Data Standards Task Force (DSTF) is developing a new Advanced Cytometry Specification (ACS). DICOM has developed and is extending a pathology extension. The work of both groups is complementary with some overlap. Interoperation would benefit both groups and permit each to benefit from the other’s expertise.

Methods: The design and implementation of the CytometryML version of the ACS schemas have been based on each schema describing one object (modularity), iterative (spiral) development, inheritance, and reuse of data-types and their definitions from DICOM, Flow Cytometry Standard, and other standards.

Results: These schemas have been validated with two tools and XML pages were generated from highest level schemas. Binary image data and its associated metadata are stored together in a zip file based container. A schema for a table of contents, which is one of the metadata files of this container, has recently been developed and reported upon. The binary image data is placed in one file in the container; and the metadata associated with an image in another. The schema for the image metadata file includes elements that are based on the DICOM design. This image schema includes descriptions of the acquisition context, image (including information on compression), specimen, slide, transmission medium, major optical parts, optical elements in one or more optical channels, detectors, and pixel format. The image schema describes both conventional camera systems and scanning or confocal systems.


R.C. Leif, J. Spidlen, R. R. Brinkman A Container for the Advanced Cytometry Standard (ACS) (preprint) to be in Manipulation and Analysis of Biomolecules, Cells, and Tissues V, D. Farkas, R. C. Leif, and D. V. Nicolau, Editors, SPIE Proc. Vol. 7182 (2009).

Abstract

Introduction: The highest priority for the Advanced Cytometry Standard (ACS) is the interpretation of list-mode cytometry measurements. Other priorities of lesser importance are the capacity to reproduce a cytometry measurement and the implementation of a digital microscopy image standard. The sequential nature of these requirements is being accommodated by a flexible, modular design. A major feature of this modular design is the creation of a design for an Advanced Cytometry Standard Container (ACSC) that includes a Table of Contents (ToC) XML file, one or more binary data containing files and files that contain the meta-data that describes the binary data.

Methods: The design and partial implementation of the CytometryML schemas have been based on the techniques of modularity (each schema describing one object), iterative (spiral) development, inheritance, and reuse. Data-types including their definitions have been reused from DICOM, FCS, and other standards.

Results: A prototype ToC schema together with prototypes of many of the schemas that describe the contents of the ACSC have been created together with their supporting schemas. These schemas have been validated with two tools and XML pages were generated from the main element(s) of the highest level schemas. These elements describe the table of contents of the zipped container file and a flow-cytometry instrument. The zipped container file (ACSC) describes and contains the meta and binary data.


R.C. Leif, J. Spidlen, R. R. BrinkmanCytometry Standards Continuumin Manipulation and Analysis of Biomolecules, Cells, and Tissues V, D. Farkas, R. C. Leif, and D. V. Nicolau, Editors, SPIE Proc. Vol. 6859 (2008).

Abstract

Introduction: The International Society for Analytical Cytology, ISAC, is developing a new combined flow and image Analytical Cytometry Standard (ACS). This standard needs to serve both the research and clinical communities. The clinical medicine and clinical research communities have a need to exchange information with hospital and other clinical information systems.

Methods: 1) Prototype the standard by creating CytometryML and a RAW format for binary data. 2) Join the ISAC Data Standards Task Force. 3) Create essential project documentation. 4) Cooperate with other groups by assisting in the preparation of the DICOM Supplement 122: Specimen Module and Pathology Service-Object Pair Classes.

Results: CytometryML has been created and serves as a prototype and source of experience for the following: the Analytical Cytometry Standard (ACS) 1.0, the ACS container, Minimum Information about a Flow Cytometry Experiment (MIFlowCyt), and Requirements for a Data File Standard Format to Describe Flow Cytometry and Related Analytical Cytology Data. These requirements provide a means to judge the appropriateness of design elements and to develop tests for the final ACS. The requirements include providing the information required for understanding and reproducing a cytometry experiment or clinical measurement, and for a single standard for both flow and digital microscopic cytometry. Schemas proposed by other members of the ISAC Data Standards Task Force (e.g, Gating-ML) have been independently validated and have been integrated with CytometryML. The use of netCDF as an element of the ACS container has been proposed by others and a suggested method of its use is proposed.


R.C. Leif CytometryML, a data standard, which has been designed to interface with other standards (preprint)   to be in Manipulation and Analysis of Biomolecules, Cells, and Tissues V, D. Farkas, R. C. Leif, and D. V. Nicolau, Editors, SPIE Proc. Vol. 6441 (2007).

Abstract

Because of the differences in the requirements, needs, and past histories including existing standards of the creating organizations, a single encompassing cytology-pathology standard will not, in the near future, replace the multiple existing or under development standards. Except for DICOM and FCS, these standardization efforts are all based on XML. CytometryML is a collection of XML schemas, which are based on the Digital Imaging and Communications in Medicine (DICOM) and Flow Cytometry Standard (FCS) datatypes. The CytometryML schemas contain attributes that link them to the DICOM standard and FCS. Interoperability with DICOM has been facilitated by, wherever reasonable, limiting the difference between CytometryML and the previous standards to syntax. In order to permit the Resource Description Framework, RDF, to reference the CytometryML datatypes, id attributes have been added to many CytometryML elements. The Laboratory Digital Imaging Project (LDIP) Data Exchange Specification and the Flowcyt standards development effort employ RDF syntax. Documentation from DICOM has been reused in CytometryML. The unity of analytical cytology was demonstrated by deriving a microscope type and a flow cytometer type from a generic cytometry instrument type. The feasibility of incorporating the Flowcyt gating schemas into CytometryML has been demonstrated. CytometryML is being extended to include many of the new DICOM Working Group 26 datatypes, which describe patients, specimens, and analytes. In situations where multiple standards are being created, interoperability can be facilitated by employing datatypes based on a common set of semantics and building in links to standards that employ different syntax.


R.C. Leif CytometryML and other data formats  in Manipulation and Analysis of Biomolecules, Cells, and Tissues III, D. Farkas, D. V. Nicolau, and R. C. Leif, Editors, SPIE Proc. Vol. 6088-0L pp. 1-7 (2006).

Abstract

Cytology automation and research will be enhanced by the creation of a common data format. This data format would provide the pathology and research communities with a uniform way for annotating and exchanging images, flow cytometry, and associated data. This specification and/or standard will include descriptions of the acquisition device, staining, the binary representations of the image and list-mode data, the measurements derived from the image and/or the list-mode data, and descriptors for clinical/pathology and research. An international, vendor-supported, non-proprietary specification will allow pathologists, researchers, and companies to develop and use image capture/analysis software, as well as list-mode analysis software, without worrying about incompatibilities between proprietary vendor formats.

Presently, efforts to create specifications and/or descriptions of these formats include the Laboratory Digital Imaging Project (LDIP) Data Exchange Specification; extensions to the Digital Imaging and Communications in Medicine (DICOM); Open Microscopy Environment (OME); Flowcyt, an extension to the present Flow Cytometry Standard (FCS); and CytometryML.

The feasibility of creating a common data specification for digital microscopy and flow cytometry in a manner consistent with its use for medical devices and interoperability with both hospital information and picture archiving systems has been demonstrated by the creation of the CytometryML schemas. The feasibility of creating a software system for digital microscopy has been demonstrated by the OME. CytometryML consists of schemas that describe instruments and their measurements. These instruments include digital microscopes and flow cytometers. Optical components including the instruments’ excitation and emission parts are described. The description of the measurements made by these instruments includes the tagged molecule, data acquisition subsystem, and the format of the list-mode and/or image data. Many of the CytometryML data-types are based on the Digital Imaging and Communications in Medicine (DICOM). Binary files for images and list-mode data have been created and read.


R.C. Leif CytometryML, Binary Data Standards  Manipulation and Analysis of Biomolecules, Cells, and Tissues II, D. V. Nicolau, J. Enderlein, R. C. Leif, and D. Farkas, Editors, SPIE Proc. Vol. 5699, pp. 325-333 (2005).

Abstract

CytometryML is a proposed new Analytical Cytology (Cytomics) data standard, which is based on a common set of XML schemas for encoding flow cytometry and digital microscopy text based data types (metadata). CytometryML schemas reference both DICOM (Digital Imaging and Communications in Medicine) codes and FCS keywords. Flow Cytometry Standard (FCS) list-mode has been mapped to the DICOM Waveform Information Object. The separation of the large binary data objects (list mode and image data) from the XML description of the metadata permits the metadata to be directly displayed, analyzed, and reported with standard commercial software packages; the direct use of XML languages; and direct interfacing with clinical information systems. The separation of the binary data into its own files simplifies parsing because all extraneous header data has been eliminated. The storage of images as two-dimensional arrays without any extraneous data, such as in the Adobe® Photoshop® RAW format, facilitates the development by scientists of their own analysis and visualization software. Adobe Photoshop provided the display infrastructure and the translation facility to interconvert between the image data from commercial formats and RAW format. Similarly, the storage and parsing of list mode binary data type with a group of parameters that are specified at compilation time is straight forward. However when the user is permitted at run-time to select a subset of the parameters and/or specify results of mathematical manipulations, the development of special software was required. The use of CytometryML will permit investigators to be able to create their own interoperable data analysis software and to employ commercially available software to disseminate their data.


R.C. Leif, S.H. Leif, S.B. Leif, CytometryML, a Markup Language for Analytical Cytology  in Manipulation and Analysis of Biomolecules, Cells and Tissues, D. V. Nicolau, J. Enderlein, and R. C. Leif, Editors, SPIE Proc. Vol. 4962 pp 288-297 (2003).

Abstract

Cytometry Markup Language, CytometryML, is a proposed new analytical cytology data standard. CytometryML is a set of XML schemas for encoding both flow cytometry and digital microscopy text based data types. CytometryML schemas reference both DICOM (Digital Imaging and Communications in Medicine) codes and FCS keywords. These schemas provide representations for the keywords in FCS 3.0 and will soon include DICOM microscopic image data. Flow Cytometry Standard (FCS) list-mode has been mapped to the DICOM Waveform Information Object. A preliminary version of a list mode binary data type, which does not presently exist in DICOM, has been designed. This binary type is required to enhance the storage and transmission of flow cytometry and digital microscopy data. Index files based on Waveform indices will be used to rapidly locate the cells present in individual subsets. DICOM has the advantage of employing standard file types, TIF and JPEG, for Digital Microscopy.

Using an XML schema based representation means that standard commercial software packages such as Excel and MathCad can be used to analyze, display, and store analytical cytometry data. Furthermore, by providing one standard for both DICOM data and analytical cytology data, it eliminates the need to create and maintain special purpose interfaces for analytical cytology data thereby integrating the data into the larger DICOM and other clinical communities. A draft version of CytometryML is available at www.newportinstruments.com.


R.C. Leif and S.B. Leif, A DICOM Compatible Format for Analytical Cytology Data, that can be Expressed in XML in Optical Diagnostics of Living Cells IV, D. L. Farkas and R. C. Leif, Editors, SPIE Proc. Vol. 4260 pp. 238-48 (2001).

Abstract

Flow Cytometry data can be directly mapped to the Digital Imaging and Communications in Medicine, DICOM standard. A preliminary mapping of list-mode data to the DICOM Waveform information Object will be presented. This mapping encompasses both flow and image list-mode data. Since list-mode data is also produced by digital slide microscopy, which has already been standardized under DICOM, both branches of Analytical Cytology can be united under the DICOM standard. This will result in the functionality of the present International Society for Analytical Cytology Flow Cytometry Standard, FCS, being significantly extended and the elimination of the previously reported FCS design deficiencies. Thus, The present Flow Cytometry Standard can and should be replaced by a Digital Imaging and Communications in Medicine, DICOM, standard. Expression of Analytical Cytology data in any other format, such as XML, can be made interoperable with DICOM by employing the DICOM data types. A fragment of an XML Schema has been created, which demonstrates the feasibility of expressing DICOM data types in XML syntax. The extension of DICOM to include Flow Cytometry will have the benefits of 1) retiring the present FCS, 2) providing a standard that is ubiquitous, internationally accepted, and backed by the medical profession,and 3) interoperating with the existing medical informatics infrastructure.


R.C. Leif and S.B. Leif, A DICOM Compatible Format for Analytical Cytology Data in Optical Investigations of Cells In Vitro and In Vivo, D. L. Farkas, R. C. Leif, B. J. Tromberg, Editors, A. Katzir Biomedical Optics Series Ed. Proc. of SPIE Vol. 3260, ISBN 0-8194-2699-7 pp. 282-289, (1998).

Abstract

The addition of a list mode data type to the Digital Imaging and Communications in Medicine standard, DICOM will enhance the storage and transmission of digital microscopy data and extend DICOM to include flow cytometry data. This would permit the present International Society for Analytical Cytology Flow Cytometry Standard to be retired. DICOM includes: image graphics objects, specifications for describing: studies, reports, the acquisition of the data, work list management, and the individuals involved (physician, patient, etc.). The glossary of terms (objects) suitable for use with DICOM has been extended to include the collaborative effort of Logical Observation Identifier Names and Codes (LOINC) and Systematized Nomenclature of Human and Veterinary Medicine (SNOMED) to create a consistent, unambiguous clinical reference terminology. It also appears that DICOM will be a significant part of the Common Object Request Broker Architecture, CORBA.


R.C. Leif and S.B. Leif, The Evolution of Flow Cytometry Standard, FCS3.0, into a DICOM Compatible Format, in Optical Diagnostics of Biological Fluids and Advanced Techniques in Analytical Cytology, Ed. A. V. Priezzhev , T. Asakura, and R. C. Leif. A. Katzir Series Editor, Progress Biomedical Optics Series , SPIE Proceedings Series, Vol. 2982, pp 354-366 (1997).

Abstract

The International Society for Analytical Cytology, ISAC,has developed a Flow Cytometry Standard (FCS) to permit data interchange. ISAC will soon replace Flow Cytometry Standard 2.0 (FCS2.0) with FCS3.0. Unfortunately,the proposed FCS3.0 is still fraught with problems, which are of sufficient magnitude as to warrant its early replacement. The most reasonable replacement is as a supplement to the Digital Imaging and Communications in Medicine, DICOM 3.0, standard. The recent digital microscopy extension of DICOM can be extended and modified to include flow cytometry data. DICOM includes: image graphics objects, specifications for describing: studies, reports,the acquisition of the data and the individuals involved, physician, patient, etc. Storing the present FCS data in a database, which has already been accomplished with the QC Tracker software, will facilitate the transition of FCS to DICOM.

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