A flexible, cost-effective platform for data generation and interpretation
Our combination of the Agilent array platform and Ingenuity Pathways Analysis informatics allows us to offer as much (or as little) support as you need – from labelling, hybridisation and raw data supply; through to signature list generation, development of mechanism-based hypotheses and biological pathways analysis. As a full-service pre-clinical contract research organisation, CXR can also perform in vitro and in vivo experimentation prior to RNA extraction.
Capabilities in both gene expression and genomic analysis | Agilent and CXR support both traditional gene expression analysis, plus cutting-edge genomic techniques to interrogate copy number (e.g. comparative genomic hybridisation - cGH), protein binding to regulatory sequences (e.g. ChIP on chip), microRNA expression and DNA methylation. |
Cost-effective multiplexed array layouts | Unlike other array platforms, Agilent supports multiple arrays per slide, allowing multiple samples to be analysed simultaneously on a single slide – increasing your experimental efficiency and reproducibility. |
Engineered for sensitivity and flexibility | Agilent’s 60-mer probes provide industry-leading sensitivity, and both one-colour (quantitative) and two-colour (comparative) labelling approaches are supported |
Rapid access to customised arrays | Agilent’s inkjet technology and web-based portal for custom array design allow rapid and cost-effective access to user-designed chipsets – or CXR can design the array for you |
Expert biological interpretation of results | We understand that statistical analysis of bioinformatic data can be overwhelming without context, which is why we combine the Agilent platform with the Ingenuity bioinformatics platform. |
Experience and support you can trust | As an Agilent-accredited service provider since 2002, CXR has played a pivotal role in the establishment of a number of cutting-edge analyses on the Agilent platform, including laser microdissection targeted expression microarray analysis of human tongue biopsy samples, and ChIP on chip array analysis of foetal rat testes samples. We offer whatever level of support you require, from simple hybridisation and raw data supply through to full experimental design and pathways analysis. |
Case Study 1
The customer was concerned about the competitive profile of one of their development compounds, and wished to compare it with the clinical market leader. We analysed kidney and liver samples from treated rats. Differences were found in key pathways involved in apoptosis, DNA damage, oxidative stress, and cell cycle control. The results demonstrated that the market leader had the potential to cause carcinogenicity over long term use, highlighting a potential commercial advantage for the customer. Armed with this knowledge, the decision was taken to continue the development of the compound.
Analysing the most challenging samples
Emerging microarray applications place a premium on the detection of sequences present at very low levels. This capability is especially valuable when analyzing complex tissue types, such as heterogeneous cell populations in tumour samples, or when using cutting-edge genomic analysis techniques (e.g. ChIP on chip, methylation analysis) where the protocol requires manipulating very small (i.e. immunoprecipitated) DNA samples.
CXR has considerable expertise in:
- Isolating individual tissues or even individual cells (for instance using laser-capture microdissection), and extracting informative RNA/DNA samples
- Immunoprecipitation enrichment of DNA from toxicological samples
- Selecting and carrying out the most appropriate labelling strategy (one vs. two cycle) using low sample input amounts (down to 50ng total RNA/DNA)
- Biological interpretation of data from such samples, for instance establishing mechanisms of toxicity at a cellular level
Investigative and Mechanistic Toxicology
At CXR, we specialise in elucidating the pathways that define the effects of chemicals on cells, tissues and whole organisms – modulation of which can result in either protective or deleterious effects. We have extensive experience in evaluating toxicological processes across species, and determining the relevance to man of observed adverse reactions to the satisfaction of regulatory bodies. Using this approach, we have ‘rescued’ compounds that may otherwise have been abandoned by industry.
CXR will work with you to design state of the art investigative safety studies to understand the mechanisms of adverse preclinical observations, interpret the results, and if required make recommendations as to the future of the project. Conversely, we can also help you identify chemicals with cytoprotective effects. Using our microarray capabilities alongside other applied preclinical and toxicological approaches allows us to unravel complex mechanisms of toxicity and to establish their relevance to man.
Using our expertise in mechanistic toxicology, CXR is validating and advising on Ingenuity’s pathways analysis software, IPA-Tox™, allowing us to deliver a focused toxicity and safety assessment of candidate compounds.
Overlaying results from Ingenuity Pathways Analysis with statistical clustering of microarray data provides new insights into the mechanisms of toxicological responses such as oxidative stress response, interactions of drugs with individual enzymes such as P450s, and xenobiotic metabolism. This is extremely useful for discovering biomarkers, assessing their relevance to humans, and evaluating the utility of toxicological models for risk assessment.
Case Study 2
CXR studied region-specific changes in gene expression and signalling pathways caused by a widely-used industrial chemical in the rat, in order to determine whether these toxicities where relevant to man. Transcription profiling was carried out using RNA isolated from laser capture microdissected interstitial cell and tubular cell regions from testes of exposed rats. Microarray analysis identified a number of pathways that were commonly altered in each cellular region, but also some that were specific to individual cell types, demonstrating that the interstitial cells appeared to be the primary target of chemical-induced dysfunction[1].
[1] Plummer et al., Toxicological Sciences 97(2), 520-532 (2007)
