Genomic copy number changes and structural rearrangements represent an important source of genetic variation. The ability to survey these changes accurately in populations and cohorts has become a must for gaining a more comprehensive view of the genome and elucidating disease mechanisms. Only Helicos lets you harness the power of True Single Molecule Sequencing (tSMS)TM for an unbiased view of CNV on hundreds to thousands of samples.

The Advantages
Helicos Single Molecule Digital CNV Analysis, an amplification-free assay with millions of reads per sample, provides you with:

• The ability to perform CNV analyses on hundreds of samples in a cost-effective manner
• The resolution to find changes not detectable on array-based platforms or amplification-based next-generation sequencers
• The precision to ensure that your results stay the same from run-to-run and from prep-to-prep
• The quantitative accuracy only possible with an amplification- and ligation-free approach

The Evidence: High resolution digital CNV maps of the human genome
Helicos has demonstrated the ability to detect copy number changes in a human cancer genome using our simple and low cost approach. Using only one channel of a 50-channel flow cell, scientists at Helicos in collaboration with a major genome center, detected known and undiscovered aberrations throughout the genome of a breast cancer cell line (see figure 1).

Figure 1. Genomic DNA samples from a breast-cancer cell line and a HapMap cell line were processed without amplification using the Helicos DNA Sample Preparation methodology described in Figure 2. Each modified DNA sample was loaded into one channel of a 50-channel Helicos Flow Cell, and analyzed using the HeliScope Single Molecule Sequencer. Single molecule reads were mapped to the human genome and copy-number changes were assessed by comparing read counts between the two samples in every location of the human genome. Results from a representative section of Chromosome 20 are shown and copy number changes are denoted by the red arrows. Results were confirmed using alternate methods.

The Approach
Native genomic DNA from a sample is sheared, modified with a poly-A tail and loaded onto the instrument. No ligation or PCR amplification steps are required. The tailed fragments hybridize to complementary poly-T strands anchored to the flow cell surface. Inside the HeliScope™ Single Molecule Sequencer, a series of nucleotide addition and detection cycles determine the sequence of each fragment. Open source data analysis software aligns the hundreds of millions of reads to a reference sequence.

Figure 2. Helicos DNA Sample Preparation Methodology

Helicos Digital CNV Analysis - The only digital and virtually bias-free CNV analysis available today.