Complete Genomics

Sequencing complete human genomes at a significantly higher throughput and much lower cost than other technologies, Complete Genomics will open up exciting new opportunities in genomic, medical, and translational research.

Complete Genomics’ sequencing center will provide an array of applications including:

Transcriptome analysis

Small RNA profiling and discovery

The majority of Mendelian diseases where a causal genetic defect has been identified are a result of rare mutations which affect protein function. To date, many genome wide association studies (GWAS) have been conducted to identify common variants that contribute to complex diseases such as diabetes, Parkinson’s, rheumatoid arthritis, and many others. However, most candidate alleles identified by GWAS contribute only small effects on disease risk. Therefore, the ability to focus on rare variants in protein coding regions of the genome, collectively known as the exome, may provide a productive avenue of investigation. Recently, studies by Choi et al. (1)and Ng et al. (2)have demonstrated the utility of exome sequencing in enabling the detection of rare variants to better understand human diseases.

Complete Genomics will expand our product offering to include full Exome sequencing in 2010. The product will use state of the art DNA capture technology to enrich for protein coding DNA and our established sequencing platform (3). Exome data will be generated with similar depth of coverage and quality as our complete genome offering.

Researchers are studying the transcriptome to better understand important cellular processes such as cell differentiation, organ damage and repair, and tumor initiation and progression. The transcriptome is the set of all RNA molecules transcribed from the genome. These RNA molecules include messenger RNAs (mRNAs), which serve as templates for protein synthesis. The transcriptome can vary with external environmental conditions, and it reflects the genes that are being actively expressed at any given time. Combining DNA and transcriptome analysis provides a comprehensive solution that will further enable researchers to understand genes and non-coding RNAs throughout the genome.

Complete Genomics plans to offer unprecedented sequencing coverage of the complete human transcriptome, including complete full length sequences and quantities of all transcribed RNA molecules. These data will help researchers identify distinguishing features in the transcriptional profile of stem and other cell types and better understand how breakdowns in molecular pathways can lead to complex diseases such as cancer.

Cancer is a complex genomic disease in which a cell’s genetic program goes awry. Distinct cancer types can arise from different tissues, and subgroups of tumors within a single tissue type may behave differently. Understanding the molecular mechanisms that drive a normal cell to become a cancerous cell requires analyses from multiple molecular angles.

Investigators are looking for ways to accelerate the identification of vulnerabilities within cancerous cells and to develop strategies to attack these targets. Understanding the molecular basis of cancer is the key to improving prevention, detection, diagnosis and treatment of this complex disease.

Complete Genomics plans to support cancer programs by providing integrated expertise in characterizing cancers’ genetic alterations:

There are several hundred microRNAs (miRNAs) encoded in the human genome whose main function is to down-regulate gene expression. Several thousand human genes, about one-third of the whole genome, are potential targets for regulation by these miRNAs.

Just as miRNA is involved in the normal functioning of cells, dysregulation of miRNA is associated with the onset of diseases such as cancer and heart disease. Researchers are studying miRNA with the goal of developing miRNA-based diagnostics and therapeutics.

Complete Genomics plans to provide a service for small RNA expression, including miRNAs, to help companies identify variability in both mature miRNA sequences and sequences that belong to novel miRNA genes.

DNA methylation plays a critical role in the regulation of gene expression and is an essential mechanism for guiding normal cellular development and for maintaining tissue identities.

DNA methylation can give rise to imprinting, i.e. the silencing of one of the alleles in a gene pair. Such imprinting can present a problem when the unmethylated allele of a gene that serves a protective function such as tumor suppression is damaged.

Researchers are interested in studying the role that DNA methylation patterns play in both common and complex diseases. The commonality of these patterns across samples of a particular phenotype may be a signature that links it to an underlying trait or disease. Quantitative methylation measurement at the single-CpG-site level offers the highest resolution for understanding such epigenetic changes. Complete Genomics' sequencing technology will enable the discovery of methylation variable positions (MVPs) across the entire genome through sequencing of bisulfite-converted DNA.