Editorial Article
Monday March 08, 2010
by Caitlin Smith
The advent of microarray technology enabled massive parallel processing of DNA (or RNA) screening experiments. Made of an orderly set of DNA spots attached to a solid support, such as a glass slide, a silicon microchip, a nylon membrane, or a bead, microarrays let researchers search for information in biological samples faster than ever before. One key to this technique is the microarray instrumentation, such as the scanner that reads the array results, plus any automation equipment that serves it. If you depend on these vital time-savers, you may benefit from this update on the latest releases in microarray instrumentation.
Arrays and sequencing in one
For researchers in need of a microarray scanner and a sequencer, Illumina is soon to launch the SQ Module for their iScan system microarray scanner. Their scanner supports genome-wide association studies, targeted and custom genotyping from 96 to 200,000 markers, gene expression, and methylation. The addition of the SQ Module will give the iScan system the ability to support next-generation sequencing as well. The SQ Module is a fluidics device that gives a new or existing iScan system Illumina's sequencing-by-synthesis technology.
“Researchers are now beginning to appreciate the complementary nature of information that arrays and sequencing can provide,” says Debora Bailey, marketing manager for DNA analysis at Illumina. “The SQ Module allows both kinds of data to be generated from the same system. For example, this enables researchers to rapidly add follow-on targeted sequencing data to their genome-wide association studies, discover new population-specific variants for further studies, and add new custom content for deeper analysis. It also allows researchers to combine sequencing and array-based gene expression data for comparison, deeper analysis and informed decisions on the optimal scientific approach to analyze their samples.” Illumina’s system is flexible in allowing you to choose the level and scale of automation that is right for you, and also offers a laboratory information management system (LIMS) positive-sample tracking system.
An important ingredient in a successful microarray protocol is software that helps you to accomplish your goals and facilitates efficient analysis. Illumina’s GenomeStudio data analysis software allows you to view and analyze all microarray-based data generated on both the iScan system and BeadXpress reader. “Performance optimized tools and a user-friendly graphical interface allow our customers to quickly and easily convert data into meaningful results,” says Bailey. “Because GenomeStudio handles data produced by all of Illumina’s platforms, our customers can use one software tool to seamlessly analyze both array and sequencing data. In addition, data generated by Illumina’s microarray platforms can be easily exported to a number of third-party software tools for further secondary and tertiary analysis through the use of plug-ins, which are integrated directly into GenomeStudio. This open-access capability is key to Illumina’s software philosophy.”
Expanding arrays’ accessibility
Unfortunately, not just anyone can take advantage of the benefits of microarray analysis. Many researchers who have a scientific need for the technology lack funds for the instrumentation, experience with the analysis, or research time to optimize conditions. Affymetrix hopes to change this with their more affordable and accessible GeneAtlas™ System. “[It] enables every biologist to characterize gene expression changes with a whole-genome view,” says Mindy Lee-Olsen, VP of field marketing at Affymetrix. “The GeneAtlas™ System includes everything a scientist needs to process Affymetrix arrays, apply statistical models, and analyze data for biological pathways. It’s unique because it meets the needs of researchers with no microarray experience. We have simplified the workflow and data analysis and made running microarrays affordable.” Affymetrix’s other microarray systems include their GeneChip® System for standard throughput experiments, and their automated GeneTitan® System for mid- to high-throughput experiments. “For individual scientists who want to use microarrays, the biggest challenges are the complexity of microarray systems and data analysis, as well as budget constraints,” notes Lee-Olsen. “Researchers have so far addressed these challenges by collaborating with someone who has a microarray system and is familiar with the data analysis, or by outsourcing. The GeneAtlas™ System addresses these unmet needs by simplifying array processing and data analysis, and at an affordable price.”
Roche NimbleGen aims to support all of its applications with their microarray instrumentation, thereby making it more accessible to researchers who have multiple analysis requirements. They recently released their MS 200 Microarray Scanner for processing of NimbleGen’s high-density arrays. “This new scanner offers scanning of multiple microarray slides at high resolution (down to 2 microns) for all current and next-generation array densities with the sensitivity required to obtain optimal results from NimbleGen arrays and a clear 'picture' of your data,” says Kary Staples, Global Marketing Communications Manager at Roche NimbleGen. “This gives us a comprehensive solution for the array market covering all of our array applications for a complete solution for CGH [Comparative Genomic Hybridization] /CNV [Copy Number Variation], ChIP [Chromatin Immunoprecipitation] -chip, DNA methylation and gene expression analysis. Additionally, we have launched our CGX Cytogenetics Solution, which comprises a full offering of arrays, reagents, and software for high-resolution copy number variant analysis for research studies in the cytogenetic research market on constitutional disorders.” The CGX Cytogenetics Solution uses Roche NimbleGen array technology, with array design by Signature Genomics, along with access to a novel and unique database from Signature Genomics via their Genoglyphix Software for data analysis.
Microarrays in the future
Despite the recent advances in microarray instrumentation, some question the future utility of microarray technology – is it an endangered species of the labware world? “Some have thought, with the advent of next-generation sequencing, that array technology will be pushed to the periphery of scientific research,” says Bailey. “For some applications, such as gene expression, this is likely the case. But for other applications, the two technologies are highly synergistic: especially in the discovery of disease associated regions, their deeper analysis, and then discovery of new variants for wider screening. The challenge to advancing microarray technologies is to focus on those developments that will yield the greatest benefits; specifically, being able to rapidly and economically deploy the new content being discovered by next generation sequencing, being able to migrate analyses to sequencing that will most benefit from this approach, and [giving] scientists the flexibility to address their evolving needs.”
An advantage that Roche NimbleGen provides is the ability to rapidly and cost-effectively add new content to an array. With their MAS (Maskless Array Synthesizer) technology, a technology for building a microarray that employs millions of micro-mirrors to pattern light onto a glass slide to create a ‘virtual mask’. This technology allows Roche NimbleGen to quickly build and create long oligonucleotides to create arrays with up to 2.1 million features and to rapidly implement the new content that is continually being discovered through next-generation sequencing.
Staples believes that a key to the future of microarray instrumentation is further improved ease-of-use along with faster turn-around times. “More and more researchers are looking for automated solutions; however, they also require a simplicity in ease-of-use while maximizing the utility of the instruments. Driving down the cost per sample is also one of the keys to advancing microarray instrumentation. Automation, therefore, will help in providing ease-of-use, less hands-on time and accuracy of data while moving to higher densities and multiplex formats. Unlike other technologies on the market, NimbleGen higher multiplex microarrays do not require a change in processing instrumentation, thereby saving on capital expenses and training costs and simplifying the processing of the arrays.”
According to Staples, it remains to be seen what effect front-end automation will have on the overall throughput, especially considering the cost of the automation, and its unknown level of uptake in the market. “While increasing probe densities and high-throughput multiplexing capabilities drive this to smaller and smaller formats, including 24-plex to 96-plex, automation will become a requirement for the sample prep and processing of these arrays,” says Staples. “This area of genomics holds significant potential as it opens up possibilities for parallel screening of thousands of samples in a shorter timeframe. Automation also has the potential to reduce experimental errors and free up the researchers to focus on analyzing the data downstream. However, a significant amount of coordination and validation of these systems is required to ensure they produce the results and quality that current, more manual systems offer.”