Biomarker Discovery and Validation Services - Phase II

Arrayit Phase II Biomarker Discovery and Validation Service includes pre-services conference, consulting, guidance and establishment of experimental design, sample preparation, and RNA isolation procedures, RNA analysis, RNA amplification, cDNA labeling, cDNA analysis, H25K hybridization, H25K processing, H25K scanning, H25K data analysis, statistical analysis of 35 million data points representing 10 control and 10 test samples, identification and up- and down-regulated genes, gene ontology analysis, full report, and post-analysis conference. Genotyping and protein expression analysis for the twenty samples are available for an additional fee.

Services - Genetic Disease Analysis, Biomarker Discovery, and Therapeutic Protein Validation using Advanced Microarray Technology and Bioinformatics

Arrayit offers full service genetic disease analysis, biomarker discovery, and therapeutic protein validation using the company’s proprietary genomic, transcriptomic, and proteomic profiling core competencies. Phase I, II, III, IV and V programs provide biomarker leads, biomarker scale-up studies, and FDA approvable data for 100, 500 and 1,000 samples, respectively, for any physiological pathway, drug response or disease state. Arrayit’s unique ability to quantitatively measure mRNA expression levels for all human genes, and to enhance the mRNA data with the ability to analyze variations in DNA sequences on a massive scale and interrogate protein samples for protein biomarkers of interest, offers leading edge biological information to customers not obtainable from any other source. Genome Pathway Builder™ analysis provides detailed biological pathways for disease analysis, small molecule drugs and therapeutic proteins. This service is highly recommended for complex disease states, orphan diseases and newly discovered genetic illnesses.

Contents

• Introduction
• Quality Control
• Services Description
• Program Phases I, II, III, IV and V
• Biomarker Platforms
• Technical Assistance
• Scientific Publications
• Ordering Information
• Warranty

Introduction
Arrayit offers premium biomarker discovery and validation services to improve the precision, speed and affordability of genomics, transcriptomics, and proteomics information for customers in the life sciences, personal genomics, pharmaceutical, and diagnostics sectors. This handbook contains all the information required to take full advantage of Arrayit's Phase I, II, III, IV and V programs.

Quality Control
Arrayit uses the highest quality control (QC) and quality assurance (QA) procedures to ensure the quality and accuracy of the information provided in our biomarker discovery and validation services.  The finest science and engineering was used to develop our transcriptomic, genomic and proteomic services products.  The most advanced bioinformatics ensure that the information provided in our Phase I, II, III, IV and V programs exceeds the highest industry standards.

Services Description
Arrayit Biomarker Discovery and Validation Services offers customers the opportunity to identify biomarkers for human diseases, physiological conditions, drug pathways and  other biological pathways that causes changes in gene expression. Expression profiling on samples of interest is performed using Arrayit’s sophisticated H25K Whole Human Genome Chip, the world’s only genome profiling platform designed using the entire human genome as the blueprint. Phase I, II, III, IV and V programs can be supplemented with value added genotyping and protein profiling information.

Customers will appreciate the following service features:

• Decipher the molecular basis of any human disease
• Explore any physiological pathway in human cells
• Elucidate the molecular mechanisms of small molecule drug action
• Discover and benchmark novel and existing therapeutic proteins
• Identify off-targets of drug toxicity
• Obtain validated biomarkers with significant commercial value
• Genome Pathway Builder™ analysis provides biological pathways for disease and drug studies
• Speed biomarker discovery
• Develop more efficacious and safer medicines
• Establish a biomarker panel for in vitro diagnostics
• Sample-to-data consulting guarantees valid results
• Comprehensive human genome content ensures complete marker set
• Proprietary two-color process affords “bullet-proof” expression markers
• Enhance marker panel with genotyping and protein expression data

Figure 1. Arrayit Phase I Biomarker Discovery and Validation Services analysis of control and neurodegenerative disease samples. The biomarker lead (arrow) is easily identified in the H25K microarray scanned image.

Program Phases I-V
The five phases of our Biomarker and Therapeutic Protein Discovery and Validation program provide the deliverables described herein. Custom programs and value-added genotyping and protein expression information are also available.

Phase I (Biomarker leads):

• Pre-services conference
• Consulting, guidance and establishment of experimental design
• Assistance with sample preparation
• Assistance with RNA isolation procedures
• RNA analysis
• RNA amplification
• cDNA labeling
• cDNA analysis
• H25K hybridization, processing and scanning
• H25K data quantification
• Comparison of 1 control and 1 test sample
• Statistical analysis of 3.5 million data points
• Identification and up- and down-regulated genes
• Gene ontology analysis
• Genome Pathway Builder™ analysis
• Full report
• Post-analysis conference

Phase II (Biomarker scale-up):

• Pre-services conference
• Consulting, guidance and establishment of experimental design
• Assistance with sample preparation
• Assistance with RNA isolation procedures
• RNA analysis
• RNA amplification
• cDNA labeling
• cDNA analysis
• H25K hybridization, processing and scanning
• H25K data quantification
• Comparison of 10 control and 10 test samples
• Statistical analysis of 35 million data points
• Identification and up- and down-regulated genes
• Gene ontology analysis
• Genome Pathway Builder™ analysis
• Full report
• Post-analysis conference

Phase III (FDA data, 100 samples):

• Pre-services conference
• Consulting, guidance and establishment of experimental design
• Assistance with sample preparation
• Assistance with RNA isolation procedures
• RNA analysis
• RNA amplification
• cDNA labeling
• cDNA analysis
• H25K hybridization, processing and scanning
• H25K data quantification
• Comparison of 100 control and 100 test samples
• Statistical analysis of 350 million data points
• Identification and up- and down-regulated genes
• Gene ontology analysis
• Genome Pathway Builder™ analysis
• Full report
• Post-analysis conference

Phase IV (FDA data, 500 samples):

• Pre-services conference
• Consulting, guidance and establishment of experimental design
• Assistance with sample preparation
• Assistance with RNA isolation procedures
• RNA analysis
• RNA amplification
• cDNA labeling
• cDNA analysis
• H25K hybridization, processing and scanning
• H25K data quantification
• Comparison of 500 control and 500 test samples
• Statistical analysis of 1.75 billion data points
• Identification and up- and down-regulated genes
• Gene ontology analysis
• Genome Pathway Builder™ analysis
• Full report
• Post-analysis conferences at 100 and 500 samples

Phase V (FDA data, 1,000 samples):

• Pre-services conference
• Consulting, guidance and establishment of experimental design
• Assistance with sample preparation
• Assistance with RNA isolation procedures
• RNA analysis
• RNA amplification
• cDNA labeling
• cDNA analysis
• H25K hybridization, processing and scanning
• H25K data quantification
• Comparison of 1,000 control and 1,000 test samples
• Statistical analysis of 3.5 billion data points
• Identification and up- and down-regulated genes
• Gene ontology analysis
• Genome Pathway Builder™ analysis
• Full report
• Post-analysis conferences at 100, 500 and 1,000 samples

Biomarker and Therapeutic Protein Platforms
Arrayit leverages the company’s unique ability to decipher gene expression, genotyping, and protein expression information on three related versions of the same patented microarray technology platform. Biomarker discovery and validation is performed using our H25K Whole Human Genome Chip. Custom, consolidated versions of H25K are available for use as a molecular test for any human disease. Arrayit Variation Identification Platform™ (VIP) technology provides a high-throughput means of sample genotyping. Protein samples arequeried using our PlasmaScan™ produce line.

H25K Whole Human Genome Chip
H25K is the first and only human genome microarray designed and manufactured using the complete human genome sequence as the blueprint, ensuring maximum hybridization efficiency and transcript coverage. H25K allows biomarker identification across 25,509 fully annotated human genes and >250,000 human transcripts, while minimizing cross-hybridization. The unparalleled sensitivity of H25K affords the finest expression biomarkers of any platform available. Our proprietary ex-situ two-color microarray platform produces more reliable biomarker data and better validation than single color platforms.

H25K Custom Microarray Subsets
Arrayit Phase I, II and III programs yield biomarker panels of extraordinary value. Our unique platform allows customers to gain access to the entire long-mer oligonucleotide content of H25K to create Custom H25K microarray subsets for in vitro molecular diagnostic testing. Arrayit offers custom manufacturing services for customers wishing to outsource their biomarker panel manufacturing needs. Customers may also purchase the H25K subset sequence information to control molecular diagnostic test manufacturing at their own facility. Arrayit’s ability to offer biomarker gene information and the physical biomarkers themselves for manufacturing is another facet of the Arrayit advantage.

Variation Identification Platform™
Arrayit’s Variation Identification Platform™ (VIP) technology allows the detection of one or more sequence variants in patient DNAs from tens, hundreds, thousands or even tens of thousands of patients in a single step. Our massively parallel VIP technology is ideally suited for Biomarker Services customers wishing to complement mRNA expression information with DNA-based SNP detection in patient samples used for human disease profiling, physiological pathway studies, drug mode of action experiments, and other applications. Arrayit offers VIP testing kit manufacturing services as an outsourcing option, and technology transfer for customers wishing to formulate proprietary test kits for their alleles of choice.

PlasmaScan™
Arrayit offers the market’s only antibody microarray containing monoclonal antibodies generated against native human plasma proteins. The PlasmaScan™ antibodies react with native human proteins with proper folding and post-translation modification to exhibit high antibody binding. The Arrayit microarray platform with the PlasmaScan™ monoclonal antibodies enables the exploration and identification of novel biomarkers in the human plasma proteome.

Figure 2. Arrayit Biomarker and Therapeutic Protein Discovery and Validation Services utilize our patented contact manufacturing technology and H25K Whole Human Genome Chips to perform “deep” gene expresson profiling.

Figure 3. Arrayit Biomarker and Therapeutic Protein Discovery and Validation Services allow our customers to benchmark the molecular mode of therapeutic protein action by identifying the cellular pathway activated or repressed when cells, animal models or patients are treated with the protein drug. This service is highly recommended for pharmaceutical companies as a supplement to clinical trials.