 ArrayXpress serves a variety of markets with advanced genomics capabilities and diagnostic product applications.
While many technologies are applicable across a wide variety of markets and applications, the unique requirements necessitate the development of optimized methods, procedures and products. Tools are a common denominator, the skills and methods to apply those tools are unique. At ArrayXpressTM we have developed domain expertise in a number of markets including bioprocess optimization for pharma and industry, diagnostics for human, plant and animal health, phytosanitary and product optimization applications for agriculture, and biomarker discovery for drug development and drug induced toxicity identification.
ArrayXpress' Applications Markets
ArrayXpressTM has experience in a wide array of markets. Our foundations were initially in plant genomics, but we quickly approached by organizations doing work in a variety of animal and human applications. This led to additions to our team and capabilities that now give us significant experience in a number of markets. Many of the same technologies and systems biology approaches are applicable across a wide variety of markets, however the methods and processes must be optimized for each application. Each new application we have faced resulted in a new set of knowledge, skills and abilities that are unique and provide a strong competitive advantage to our partners and clients. We have always exceeded our client's performance requirements in any applications field we have addressed. Examples of some of our specific project area are listed below, with a detailed description of the approaches used following later in the page.
BioMarker Discovery
Animal and Plant Genotyping
Crop and Livestock Improvement
Food Safety
Human Diagnostics
Industrial Bioprocesses
Agricultural Regulatory Management
BioMarker Discovery
Biomarkers are measurable analytes used to evaluate a biological process or the body’s response to that process. For instance, a biomarker is used as an indicator of a pathological process, such as a disease, or a pharmacological process, such as response to therapy. With the convergence of genomics and clinical practice, nowadays, nucleic acids and their relevant sequence variations are commonly used as molecular biomarkers.
Biomarkers in Drug Development and Toxicity
Currently, the inability to better predict the safety and efficacy of a drug in the development pipeline is a major road block for the pharmaceutical industry. Biomarkers can be invaluable tools for exactly this purpose and are a central component of the Critical Path Opportunities identified and advocated by the FDA. Biomarkers can provide very sensitive and specific information about a drug: its mechanism of action, safety and efficacy; therefore, it can significantly benefit both preclinical and clinical drug studies. Biomarkers can also be used as pharmacodynamics indicators to monitor the drug’s metabolic processes inside the body.
Biomarkers hold the promise to empower health care workers and physicians to predict a patient’s response to the prescribed therapy before the actual treatment is initiated, identifying those who will benefit the most and those who are at greater risk of developing adverse reactions. The widely marketed promise of personalized medicine is heavily based on the use of biomarkers in the clinic. Dosing, decision of treatment regimen, early efficacy evaluation, are all examples of potential benefits of a more informed therapy guided process. Later on, some of the advantages of incorporating biomarkers in the clinic are allowing for patient stratification and selection and the use of surrogate endpoints. While drug developers can take advantage of such knowledge to better design new drugs, ultimately, the greatest beneficiaries are the patients themselves.
Cancer Research
Cancer research is certainly an area to most significantly reap the benefits of molecular biomarker discovery and application in the clinic. Even tough two patients may have tumors that largely resemble each other according to traditional morphological and histological criteria and are thus classified as belonging to the same type, their tumors can have a very different response to chemotherapy. Specific genetic changes in the patients’ tumor genetic information, for example, variations in the DNA sequence, can largely affect chemotherapy efficacy and toxicity. As the genetic background of each of us is unique, so are tumors that may arise due to faults in our genetics or due to inflicting external hazards. In other words, each cancer is unique. Not only biomarker discovery can be used to effectively guide cancer drug development and early-stage clinical trials, but once identified, biomarkers can be employed to ensure high treatment success.
Genetic Disorders
Genetic testing has witnessed some remarkable advances and is increasingly becoming more and more standard practice in medicine. Genetic disorders are caused by abnormal variations in the DNA sequence of a person. For many disorders, the underlying genetic cause is known while for others, it is still a mystery. Unveiling the genetic abnormality that leads to the development of a disease can have profound effects for those carrying the abnormal DNA and potentially save lives.
Using integrated, genome wide approaches to biomarker discovery
ArrayXpress has developed an assay for Biomarker discovery using a new and powerful animal model that accurately portrays the genetic heterogeneity of the human species. Many of the traditionally used approaches and models used for biomarker discovery are severely limited in many ways. For example, they may lack the genetic diversity necessary to model the trait under investigation, or they may have pre-made assumptions of which genes are controlling such trait. By contrast, our approach takes an unbiased look at the entire genome for variations in the DNA sequence and how these variations correlate with changes in gene expression profiles. By combining the two datasets, we can zoom in into very specific and short regions and identify genetic variants highly correlated with the phenotype of interest. These genes will be the candidate biomarkers, which need further validation studies using nucleic acid technologies, including genotyping and expression profiling, to examine their functional significance. Once their role in the studied trait is confirmed, pilot pre-clinical and clinical studies are necessary to evaluate their translational applicability to the clinic.
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Animal and Plant Genotyping
Genotyping is the process of determining the genetic profile, or genotype, of an organism, like a DNA-based fingerprint. Several methods can be used to this purpose, in which an investigator will look at the individual’s genetic profile at various markers. These molecular markers represent variations in the DNA sequence of an organism. Such variations may occur as insertions, deletions of single nucleotide polymorphisms (SNPs). The more traditional molecular genotyping methods include RAPD, RFLP, AFLP, microsateliltes (SSRs) , and other PCR-based assays. On the other hand, large scale, genome wide genotyping requires more sophisticated technologies and has the power to generate dense genetic maps. These are particularly useful for marker-assisted breeding and genetic improvement in agriculture.
Genotyping has several applications. It can be used to screen for economically advantageous traits, herd management, establishing parentage and ownership, pedigree analysis, marker assisted breeding, disease eradication programs, quality assurance, forensics, patent protection, tracing commodities from source (farm, packing plant, butcher shop, etc.) to shelf food product (bagged vegetables, packed steaks, etc.) and many more. For research purposes, it is also extremely valuable in evolutionary studies, population genetics, and germplasm evaluation.
ArrayXpress specializes in providing state of the art comprehensive DNA genotyping profiling specifically SNP identification with quick turnaround using:
Illumina's Golden Gate Genotyping Technology, (detect ~384-1536 loci simultaneously)
Illumina's Infinium Whole-genome genotyping technology (detect ~300,000-1,000,000 loci simultaneously)
Ilumina's Now/Next Generation Sequencing technology (generating >75 bp reads for a total of > 20-100 Gb of paired-end data per run)
Roche's 454 Next Generation Sequencing technology (454 Life Sciences) generating up to 1Gb of long sequence reads(~400bp reads) in a single run
PCR-based assays such as Single Sequence Repeat analysis (SSR)
Taqman/SYBR Grean Real-time PCR assays
Our team of scientists has extensive experience in the field and can assist you in selecting the most appropriate technology and designing a genotyping assay customized to your needs.
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Crop and Livestock Improvement
The genetic improvement of crops and livestock can be greatly advanced by the development of genetic markers to direct breeding efforts and programs. Identifying relevant markers is not an easy task as most agronomic traits of economic interest are determined by multiple genes (polygenic).
ArrayXpress utilizes different approaches to assist you in your marker selection and genetic improvement efforts. Using qualitative microarray technology and/or quantitative high throughput Now/Next Generation Sequencing technology (e.g. RNA-seq), the expression profile of thousands of genes can be simultaneously analyzed. The information generated can then be used to dissect complex patterns of multi-gene inheritance and assign possible functions for uncharacterized genes. Likewise gene expression analysis can unveil novel genes that are involved in a desired phenotypic trait; characterize mutant varieties and lineages; decipher molecular networks and pathways; and assess genetic epistasis. More recently, gene expression data have also proven powerful tools in quantitative genetics. Quantitative genetics approaches study continuous traits that are regulated by multiple genes or Quantitative Trait Loci (QTL). Most economically relevant traits in the agricultural sector follow a quantitative pattern. At the molecular level, QTL are very difficult to pinpoint. Using recombinant inbred lines or back-crossed populations, transcription profiling can unleash the true power of genome-wide QTL analysis in discovering genes, called expression QTL (eQTL), that regulate the trait(s) of interest. An integrated approach that further incorporates metabolic profiling and phenotypic studies has a great promise for marker discovery and genetic improvement. In addition to traditional transcript profiling, high density tilling arrays can be used for the same purpose. Their advantage is to cover the entire genome, also screening for intergenic and untranslated regions (e.g. non-coding regulatory small RNAs). The discovery of differences in the DNA sequence, also known as polymorphisms, at the whole genome level is an extremely powerful application to crop and livestock breeding and trait improvement.
A powerful strategy for high throughput, quantitative gene expression analysis, as well as molecular marker discovery, is through the application of Next Generation Sequencing technology, by either using Illumina's Genome Analyzer II or HiSeq2000 platforms, or the Roche 454 sequencing system (Life Sciences Corporation, Roche), or using both platforms in combination. The new 454 GS FLX Titanium series reagents and software provide individual sequencing reads with improved length (up to ~500 bp reads) and sequence accuracy equal or higher than 99% and a five-fold increase in throughput to 400 – 600 million base pairs per instrument run. A strategy of using both 454 long-read and Illumina GAII/HiSeq2000 short-read sequence in combination is particularly powerful when working with species whose genome is not yet sequenced. Using this approach, quantitative levels of mRNA can be generated. In silico expression profiling is then determined according to the frequency that each gene is found in each different cDNA tissue specific library. This technique has proven to be a powerful tool for gene discovery (identification of agronomically useful genes), SNPs discovery, gene mapping, analysis of quantitative traits, development of EST-derived (simple sequence repeat) SSR markers, significantly contributing to accelerate breeding programs. The precision and sensitivity of this approach is unprecedented.
Several different agronomic traits must be accounted for in order to effectively develop and implement breeding and product quality improvement efforts. To find out more how the combination of these powerful technologies and innovative approaches can have a tremendous, positive impact on your genetic improvement research and program, make sure to contact our expert team. Please refer to our Crop Improvement White Paper on this topic.
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Food Safety
The United States food supply is considered one of the safest in the world. Yet, according to the CDC each year there are 76 million cases of food-borne illness, more than 300,000 hospitalizations with 5,000 people dying. Foods can get contaminated during their natural growth (fruits and vegetables), harvest, when they are processed by the food industry and even during storage, shipment or preparation. Several microorganisms can cause food contamination and lead to food-borne illness, for instance, parasites, viruses and harmful bacteria such as E. coli, Salmonella, Listeria, Campylobacter, Clostridium, Vibrio, Giardia, and many more.
ArrayXpress has developed the AXPressDX™ assay for the rapid detection and identification of pathogens associated with food-borne illness. This novel, but scientifically validated approach can provide very fast results and is highly customizable and flexible. Moreover, the major advantage of the AXPressDX™ technology for microorganism detection is the ability to simultaneously screen for a very large number of infectious agents, with a significant increase in sensitivity, specificity, and throughput.
In collaboration with scientists at North Carolina State University’s School of Veterinarian Medicine, as well as scientists at the Food and Drug Administration (FDA), ArrayXpress has also developed a novel multiplex assay to detect four bacterial food-borne pathogens from the genera Salmonella, Campylobacter, Yersinia, and a Norovirus. Our proprietary highly multiplex, high throughput SNP-based assay is a powerful tool that can simultaneously detect multiple strains of these important pathogens within 48 hours of sample receipt to ensure the quality and safety of the food provided to the consumers.
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Human Diagnostics
Molecular diagnostics, also called MDx, is the analysis of DNA, RNA, or protein biomarkers (analytes) with the final goal of detecting a disease or its causative agent. Recent technological advances have tremendously increased our capacity to recognize minute changes in the levels of these key biological molecules much faster and more precisely. It holds the promise of significantly enhancing our ability to effectively accomplish the early detection and diagnosis of disease states. MDx is one of the fastest growing and most exciting areas in modern medicine. Particularly, the dynamic sector of nucleic acid-based diagnostics tests, called NATs, is expected to grow to $3.3 billion in 2010.
Molecular diagnostics can be used in a wide range of applications. For instance, is can be used to identify individuals at high risk to develop certain conditions, for disease diagnosis and prognosis (or predicting the disease outcome), evaluating therapy response, and in guiding physicians and healthcare professionals in better determining a patient’s treatment and therapy dosing and schedule, the broadly advertised and most wanted pledge of personalized medicine.
ArrayXpress has developed the AXPressDX™ detection assay. The technology is a rapid, highly specific (SNP-based), highly sensitive, robust, cost effective, high-throughput and culture independent molecular detection system that provides for the simultaneous identification of multiple pathogens in a single assay.
The AXPressDX™ technology – the ultimate solution for your DX needs
The AXPressDX™ detection assay is a microarray platform independent assay that provides for target-specific molecular recognition. Using single nucleotide polymorphism (SNP) detection, it significantly increases diagnostic sensitivity and multiplexing capabilities without limiting the range of potential targets. The major advantage of our assay is the ability to allow for virtually unlimited and simultaneous target screening capability with significant increases in the levels of sensitivity, specificity (SNP-based detection), and throughput capacity. The assay is easily modifiable and extendable to include new targets on demand in response to your customized need with virtually no trade costs to update tests based on new or emerging information. Our proprietary AXPressDX™ probes are custom designed by our dedicated bioinformatics team to match the target nucleic acid. Reaction run-times are comparable to real-time PCR, but with the benefit that the presence of multiple targets and pathogens and their various genotypes, serotypes, and subtypes can be analyzed within the same reaction.
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Industrial Bioprocesses
ArrayXpress provides research and development services based on first-in-class NGS and bioinformatics to increase the performance, speed, and cost effectiveness of bioprocess development and biomanufacturing. The flow of applications and techniques we provide to partners are presented in the figure below. NGS technologies provide an eagle’s-eye view into cellular metabolism and physiology, under changing growth and production conditions, applicable from the selection of a specific cell or microorganism, through bioprocess development/scale-up, and into commercial manufacturing.
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Agricultural Regulatory Management
Every year in the US agricultural business sector, billions of dollars are lost to diseases caused by a diversity of plant and animal pathogens. Disease management is critical to minimize the impact of such events on the farmers, the supply of food and feed, the environment and the economy. The economical significance of plant and animal disease outbreaks on local and global economies and trade is tremendous.
Recently, the worldwide incidence of some highly contagious transboundary animal diseases such as FMD (1997-2001), Classical Swine Fever (CSF) in the Caribbean and Europe (1996-2002), the extension of rinderpest into the Somali plains (2001), and of Rift Valley fever into the Arabian Peninsula (2000) is on the rise. The enormous economic and social impact of these animal disease outbreaks can be felt as decreased consumption and meat trading and altered meat prices. Additional ripple effects transcend the direct impact on livestock industries and impose higher costs on the input industries and the broader economy. In addition, an even greater challenge brought by animal diseases is the potential risk of disease transmission to humans. Recent examples of such zoonotic diseases include the H5N1 avian influenza virus, H1N1 swine influenza virus and Bovine Spongiform Encephalopathy (BSE), which is linked to variant Creutzfeldt-Jakob disease. It is estimated that the cost of the 1996 UK BSE outbreak to the UK economy was of US$3.828 billion. Animal welfare is very important. Imagine the savings for producers and consumers of animal agriculture if a rapid test could diagnose diseases, infections and immune system status. We could save lives, increase productivity, protect investments and more. The animal diagnostic market is over $1 billion per year and is projected to further grow.
Likewise, the introduction of non-native invasive organisms leads to tremendous economical and ecological losses. In the United States alone, economic impacts associated with non-native invasive organisms are estimated to exceed $137 billion per year. Plants are particularly vulnerable, and are subjected to attacks by over 50,000 different pathogens, primarily fungi, viruses, and bacteria, as well as nematodes and insects. For any given region and crop, producers may deal with 10 to 15 serious plant diseases and pests that can cause severe economic losses. For instance, in forestry, the introduction of alien forest insects and pathogens are estimated to cause approximately $4.2 billion (BEA) in annual losses to business. This is mainly in the form of reduced timber yields caused by growth loss and increased mortality, as well as increased costs for control and management operations. The precise identification of microbial plant pathogens, nematodes or insects affecting economically important plants or plant products is an essential step for obtaining high-quality and safe production.
Timing is quintessential to a well planned, prepared and coordinate response to these events. A scientifically based disease management response can significantly minimize the impact and damage caused to the agricultural sector. Central to such responses is the ability to quickly and precisely diagnose the inflicting agent. Presently, the lack of diagnostic tools that can rapidly detect and accurately identify endemic as well as exotic high risk pathogens is a major roadblock to an effective sanitary control. With the global trade of plant and animal based products dramatically increasing, the rising risk of unintentional introduction of exotic pathogens has significant implications to the agriculture in the United States. This inability to detect, identify and quantify plant and animal pathogens and pests in a timely manner has pushed the development of new, organism-independent, molecular-based diagnostic tools for the rapid and accurate detection and identification of high risk microorganisms.
ArrayXpress has developed the AXPressDX™ assay for the rapid detection and identification of pathogens associated with plant and animal diseases. This novel, yet scientifically validated approach can provide very fast results and is highly customizable and flexible. Moreover, the major advantage of the AXPressDX™ technology for microorganism detection is the ability to simultaneously screen for a very large number of infectious agents, with a significant increase in sensitivity, specificity, and throughput.
Through strategic partnerships with both local and national organizations such as the National Science Foundation, North Carolina Biotechnology Center, USDA-APHIS, National Pork Board, and top-notch scientists from various Universities, ArrayXpress has successfully developed a broad portfolio of diagnostic products within the phyto/veterinarian pathogen arenas. For instance, in close collaboration with specialized veterinarians, we have developed a novel assay to rapidly identify pathogens associated with the Porcine Respiratory Disease Complex (PRDC) in pigs. This disease complex is caused by various Swine Influenza A Virus subtypes (H1N1; H1N2; H1N7; H3N2), as well as a DNA Porcine Circovirus 2 (PCV2), that act in synergy with Mycoplasma hyopneumoniae and other opportunistic bacterial pathogens. In the phytosanitary arena, we have developed a pathogen specific diagnostic assay that allows for early and accurate detection and identification of major forestry pathogens/pests of both economical and regulatory concern, including Phytophthora ramorum (Sudden Oak Death), Fusarium circinatum (Pitch canker of pine), Amylostereum areolatum (Sirex noctilio wood wasp fungus), Xylella fastidiosa (leaf scorch of sycamores), Phomopsis pseudotsugae (Douglas Fir Canker), and Cronartium quercuum f.sp. fusiforme (Fusiform rust fungus).
Our experienced scientific team can further assist you in selecting, designing and developing customized diagnostic panels according to your specific needs, in a cost-effective manner, with the highest quality standards and in compliance to desired regulatory and sanitary standards.
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