Cellomics

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An example of cellomics software interface. Cellomics software.png
An example of cellomics software interface.

Cellomics is the discipline of quantitative cell analysis using bioimaging methods and informatics with a workflow involving three major components: image acquisition, image analysis, and data visualization and management. These processes are generally automated. All three of these components depend on sophisticated software to acquire qualitative data, quantitative data, and the management of both images and data, respectively. Cellomics is also a trademarked term, [1] [2] which is often used interchangeably with high-content analysis (HCA) or high-content screening (HCS), but cellomics extends beyond HCA/HCS by incorporating sophisticated informatics tools.

Microscopy technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye

Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye. There are three well-known branches of microscopy: optical, electron, and scanning probe microscopy, along with the emerging field of X-ray microscopy.

Image analysis is the extraction of meaningful information from images; mainly from digital images by means of digital image processing techniques. Image analysis tasks can be as simple as reading bar coded tags or as sophisticated as identifying a person from their face.

Data visualization is the graphic representation of data. It involves producing images that communicate relationships among the represented data to viewers of the images. This communication is achieved through the use of a systematic mapping between graphic marks and data values in the creation of the visualization. This mapping establishes how data values will be represented visually, determining how and to what extent a property of a graphic mark, such as size or color, will change to reflect change in the value of a datum.

Contents

History

HCS and the discipline of cellomics was pioneered by a once privately held company named Cellomics Inc., which commercialized instruments, software, and reagents to facilitate the study of cells in culture, and more specifically, their responses to potentially therapeutic drug-like molecules. In 2005, Cellomics was acquired by Fisher Scientific International, Inc., [3] now Thermo Fisher Scientific, which continues developing cellomics-centered products under its Thermo Scientific™ high content analysis product line.

Applications

Like many of the -omics, e.g., genomics and proteomics, applications have grown in depth and breadth over time. Currently there are over 40 different application areas that cellomics is used in, including the analysis of 3-D cell models, angiogenesis, and cell-signalling. Originally a tool used by the pharmaceutical industry for screening, cellomics has now expanded into academia to better understand cell function in the context of the cell. [4] Cellomics is used in both academic and industrial life-science research in areas, such as cancer research, neuroscience research, drug discovery, consumer products safety, and toxicology; however, there are many more areas for which cellomics could provide a much deeper understanding of cellular function.

Genomics discipline in genetics

Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes. In contrast to genetics, which refers to the study of individual genes and their roles in inheritance, genomics aims at the collective characterization and quantification of all of an organism's genes, their interrelations and influence on the organism. Genes may direct the production of proteins with the assistance of enzymes and messenger molecules. In turn, proteins make up body structures such as organs and tissues as well as control chemical reactions and carry signals between cells. Genomics also involves the sequencing and analysis of genomes through uses of high throughput DNA sequencing and bioinformatics to assemble and analyze the function and structure of entire genomes. Advances in genomics have triggered a revolution in discovery-based research and systems biology to facilitate understanding of even the most complex biological systems such as the brain.

Proteomics study of proteins

Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions. The term proteomics was coined in 1997, in analogy to genomics, the study of the genome. The word proteome is a portmanteau of protein and genome, and was coined by Marc Wilkins in 1994 while he was a Ph.D. student at Macquarie University. Macquarie University also founded the first dedicated proteomics laboratory in 1995.

Angiogenesis blood vessel formation when new vessels emerge from existing vessels

Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise. The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease.

Image analysis

With HCA at its core, cellomics incorporates the flexibility of fluorescence microscopy, the automation and capacity of the plate reader, and flow cytometry’s multi-parametric analysis in order to extract data from single-cells or from a population of cells. [5]

Once an image is acquired using high content technology hardware, cell data is extracted from that image using image analysis software. Single cell data or population data may be of interest, but for both, a series of steps is followed with varying degrees of user interaction depending on the application and the software being used. The first step is segmenting the cells in the image which provides the software algorithms with the information it needs for downstream processing of individual cell measurements. Next, a user must define the area(s) of interest based on a multitude of parameters, i.e., the area a user wants to measure. After the area of interest has been defined, measurements are collected. The measurements, oftentimes referred to as features, are dictated by the type of data desired from the sample. There are many mathematical algorithms powering all of these steps, and each image analysis software package provides its own level of openness to the mathematical algorithms being used.

Data management

Large numbers of images and amounts of data need to be managed when doing cellomics research. Data and image volumes can quickly range from 11MB to 1TB in less than a year, which is why cellomics uses the power of informatics to collect, organize, and archive all of this information. Secure and effective data mining requires the associated metadata to be captured and integrated into the data management model. [6] Due to the critical nature of cellomics data management, implementing cellomics studies often requires inter-departmental cooperation between information technology and the life science research group leading the study.

Related Research Articles

Bioinformatics Software tools for understanding biological data

Bioinformatics is an interdisciplinary field that develops methods and software tools for understanding biological data. As an interdisciplinary field of science, bioinformatics combines biology, computer science, information engineering, mathematics and statistics to analyze and interpret biological data. Bioinformatics has been used for in silico analyses of biological queries using mathematical and statistical techniques.

A geographic information system (GIS) is a system designed to capture, store, manipulate, analyze, manage, and present spatial or geographic data. GIS applications are tools that allow users to create interactive queries, analyze spatial information, edit data in maps, and present the results of all these operations. GIS sometimes refers to geographic information science (GIScience), the science underlying geographic concepts, applications, and systems.

Computational archaeology describes computer-based analytical methods for the study of long-term human behaviour and behavioural evolution. As with other sub-disciplines that have prefixed 'computational' to their name, the term is reserved for methods that could not realistically be performed without the aid of a computer.

SPSS Statistical analysis software

SPSS Statistics is a software package used for interactive, or batched, statistical analysis. Long produced by SPSS Inc., it was acquired by IBM in 2009. The current versions (2015) are named IBM SPSS Statistics.

Affymetrix, Inc. was an American company that manufactured DNA microarrays; it was based in Santa Clara, California, United States. The company was acquired by Thermo Fisher Scientific in March 2016.

Yippy

Yippy is a metasearch engine that groups search results into clusters. It was originally developed and released by Vivísimo in 2004 under the name Clusty, before Vivisimo was later acquired by IBM and Yippy was sold in 2010 to a company now called Yippy, Inc. At the time, the website received 100,000 unique visitors a month.

Capability Maturity Model Integration (CMMI) is a process level improvement training and appraisal program. Administered by the CMMI Institute, a subsidiary of ISACA, it was developed at Carnegie Mellon University (CMU). It is required by many United States Department of Defense (DoD) and U.S. Government contracts, especially in software development. CMU claims CMMI can be used to guide process improvement across a project, division, or an entire organization. CMMI defines the following maturity levels for processes: Initial, Managed, Defined, Quantitatively Managed, and Optimizing. Version 2.0 was published in 2018. CMMI is registered in the U.S. Patent and Trademark Office by CMU.

Spectronic 20

The Spectronic 20 is a brand of single-beam spectrophotometer, designed to operate in the visible spectrum across a wavelength range of 340 nm to 950 nm, with a spectral bandpass of 20 nm. It is designed for quantitative absorption measurement at single wavelengths. Because it measures the transmittance or absorption of visible light through a solution, it is sometimes referred to as a colorimeter. The name of the instrument is a trademark of the manufacturer.

CellProfiler is free, open-source software designed to enable biologists without training in computer vision or programming to quantitatively measure phenotypes from thousands of images automatically. Advanced algorithms for image analysis are available as individual modules that can be placed in sequential order together to form a pipeline; the pipeline is then used to identify and measure biological objects and features in images, particularly those obtained through fluorescence microscopy.

High-content screening (HCS), also known as high-content analysis (HCA) or cellomics, is a method that is used in biological research and drug discovery to identify substances such as small molecules, peptides, or RNAi that alter the phenotype of a cell in a desired manner. Hence high content screening is a type of phenotypic screen conducted in cells involving the analysis of whole cells or components of cells with simultaneous readout of several parameters. HCS is related to high-throughput screening (HTS), in which thousands of compounds are tested in parallel for their activity in one or more biological assays, but involves assays of more complex cellular phenotypes as outputs. Phenotypic changes may include increases or decreases in the production of cellular products such as proteins and/or changes in the morphology of the cell. Hence HCA typically involves automated microscopy and image analysis. Unlike high-content analysis, high-content screening implies a level of throughput which is why the term "screening" differentiates HCS from HCA, which may be high in content but low in throughput.

Jason Swedlow is an American-born cell biologist and light microscopist who is Professor of Quantitative Cell Biology at the School of Life Sciences, University of Dundee, Scotland. He is a co-founder of the Open Microscopy Environment and Glencoe Software.

Thermo Fisher Scientific American biotechnology company

Thermo Fisher Scientific is an American biotechnology product development company located in Waltham, Massachusetts, and was created in 2006 by the merger of Thermo Electron and Fisher Scientific. In April 2013, after a competitive bidding with Hoffmann-La Roche, Thermo Fisher acquired Life Technologies Corporation for US$13.6 billion in a deal that would rank the firm as one of the leading companies in the genetic testing and precision laboratory equipment markets.

High throughput cell biology is the use of automation equipment with classical cell biology techniques to address biological questions that are otherwise unattainable using conventional methods. It may incorporate techniques from optics, chemistry, biology or image analysis to permit rapid, highly parallel research into how cells function, interact with each other and how pathogens exploit them in disease.

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Automated tissue image analysis

Automated tissue image analysis is a process by which computer-controlled automatic test equipment is used to evaluate tissue samples, using computations to derive quantitative measurements from an image to avoid subjective errors.

Bioimage informatics is a subfield of bioinformatics and computational biology. It focuses on the use of computational techniques to analyze bioimages, especially cellular and molecular images, at large scale and high throughput. The goal is to obtain useful knowledge out of complicated and heterogeneous image and related metadata.

Rockford, IL-based Pierce Chemical Company was founded in 1948 when Dr. Alan Pierce assumed active management of a company known as Midwest Extraction, which focused on extracting chlorophyll from alfalfa. Chlorophyll, the material that lends a green color to plants, was discovered in the 1930s to have therapeutic uses including the treatment of infections and burns and was useful for performing amputations.

The Colocalization Benchmark Source (CBS) is a free collection of downloadable images to test and validate the degree of colocalization of markers in any fluorescence microscopy studies. Colocalization is a visual phenomenon when two molecules of interest are associated with the same structures in the cells and potentially share common functional characteristics.

Pipeline Pilot is a desktop software program developed by Accelrys Enterprise Platform to process and analyze data. Originally used in the natural sciences, the product's basic ETL and analytics capabilities have been broadened. The product is now used for data science, ETL, reporting, prediction and analytics in a number of sectors. The main feature of the product is the ability to design data workflows using a graphical user interface. The program is an example of visual and dataflow programming. It has use in a variety of settings, such as cheminformatics and QSAR, Next Generation Sequencing, image analysis, and text analytics.

Vaa3D is an Open Source visualization and analysis software suite created mainly by Hanchuan Peng and his team at Janelia Research Campus, HHMI and Allen Institute for Brain Science. The software performs 3D, 4D and 5D rendering and analysis of very large image data sets, especially those generated using various modern microscopy methods, and associated 3D surface objects. This software has been used in several large neuroscience initiatives and a number of applications in other domains. In a recent Nature Methods review article, it has been viewed as one of the leading open-source software suites in the related research fields. In addition, research using this software was awarded the 2012 Cozzarelli Prize from the National Academy of Science.

References

  1. ↑ "Cellomics" (Web). USPTO. United States Patent and Trademark Office. Retrieved 2014-06-30.
  2. ↑ "Cellomics (informatics)" (Web). USPTO. United States Patent and Trademark Office. Retrieved 2014-06-30.
  3. ↑ "Fisher acquires Cellomics for $49M". Pittsburgh Business Times. 2005.
  4. ↑ Publications Master List. Thermo Fisher Scientific. 2014.
  5. ↑ Liszewski, Kathy (2014). "High Content Analysis: The 'Just Right' Solution". Gen. Eng. Biotechnol. News. 34 (3).
  6. ↑ Haney, Steven A. (2008). High Content Screening. Hoboken, New Jersey: John Wiley & Sons. pp. 13–14, 32.
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