High Resolution, Improved Performance, Ultimate Confidence

• High Resolution: Up to 4.2 million probes per array enables unbiased, genome-wide detection of CNVs down to ~1.4 – 5 Kb resolution (see Figure 1 and Figure 2).
• Cost-Effective Solution: Utilize NimbleGen multiplex array formats to simultaneously analyze 1, 3, 6 or 12 independent sample pairs on a single slide (see Figure 2).
• Comprehensive CNV Detection: Enhanced probe coverage of low-copy repeat regions of the genome (e.g. segmental duplications) enable increased detection of CNVs associated with pathogenic rearrangements (see Figure 3).
• Improved Performance: NimbleGen Human CGH Whole-Genome Arrays consist of empirically tested probes that provide improved data quality (i.e. signal-to-noise) compared with computationally selected probes (see Figure 4).
• Complete Flexibility: The inherent flexibility of Roche NimbleGen’s array technology enables the rapid prototyping of custom array designs, which can include whole genomes, single chromosomal regions, or multiple loci of interest. Custom designs can be created with uniform or mixed-density probe spacing using the most current genome sequence from any eukaryotic genome.

Figure 1

Figure 1. Test and reference gDNAs were independently labeled with fluorescent dyes, co-hybridized to a NimbleGen Human CGH 2.1M or 385K Whole-Genome Tiling array, and scanned using a 5 µm scanner. Log2-ratio values of the probe signal intensities (Cy3/Cy5) were calculated and plotted versus genomic position using Roche NimbleGen NimbleScan software. Data are displayed in Roche NimbleGen SignalMap software. Figure 1 shows the increased detection of copy number changes using NimbleGen CGH 2.1M Whole-Genome Tiling v2.0D arrays (1.1kb median probe spacing) compared with the 385K Whole-Genome Tiling v1.0 array (6kb median probe spacing). The increased probe density on the 2.1M array enables detection of a novel ~3kb CNV that was identified by only a single probe on the 385K array (blue arrows). In addition, fine structure of a previously reported CNV region was further elucidated using the 2.1M array.

Figure 2

Figure 2. Cross-Platform Analysis of a Large (~4Mb) Deletion Region in Chromosome 22 in a VCFS Sample Referenced Against Normal Genomic DNA: A deletion region associated with Velocardiofacial Syndrome (VCFS) is detected using three different NimbleGen CGH Whole-Genome Tiling arrays, as indicated. Copy number analysis was performed using the segMNT algorithm, available in NimbleScan software. Data are displayed using a GFF file in SignalMap software* alongside annotation tracks (provided with NimbleGen CGH arrays) showing a cytogenetic ideogram, known genes, and “normal” CNVs from the Database of Genomic Variants (http://projects.tcag.ca/variation). The red arrows indicate a presumably “normal” CNV detected by a single probe on the 12x135K array and many probes on the 3x720K and 2.1M arrays.

Figure 3

Figure 3. Analysis of a Complex CNV Region in Chromosome 17 in a Burkitt Lymphoma Research Sample as Referenced against Normal Genomic DNA. An ~382kb deletion region and an ~35kb amplification are detected using the Human CGH 2.1M Whole-Genome Tiling v2.0D array (Panel A) and the Human CGH 3x720K Whole-Genome Tiling v3.0 array (Panel B) but missed using a lower-resolution competitor’s array. Copy number analysis was performed using NimbleScan software. Data are displayed in GFF format in SignalMap software alongside annotation tracks (provided with Roche NimbleGen CGH arrays) showing corresponding “normal” CNVs, segmental duplications, and known genes. The ~382kb deletion region coincides with segmental duplications that are poorly represented on the competitor’s array. The ~35kb amplification coincides with a “normal” CNV region annotated in the Database of Genomic Variants. The competitor’s array has probe coverage of this region but lacks the resolution to detect the CNV.

Figure 4

Figure 4. NimbleGen Human CGH 3x720K and 12x135K Whole-Genome Tiling v3.0 arrays consist of empirically tested probes that show improved performance compared with the v2.0 arrays. (A) Compared with the v2.0 array (blue), the Human CGH 3x720K Whole-Genome Tiling v3.0 array (orange) offers improved signal-to-noise, which is further enhanced using the NimbleGen MS 200 Microarray Scanner at 2µm resolution (red). (B) A significant decrease in experimental noise, as measured by mad.1dr and DLRS, is achieved using the NimbleGen MS 200 Microarray Scanner at 2µm resolution. Similar results were obtained using the Human CGH 12x135K Whole-Genome v3.0 Array (data not shown).

CGH/CNV Delivery Workflow

Customers can purchase NimbleGen whole-genome or custom targeted arrays and perform CGH/CNV experiments in their own lab or core facility. NimbleGen arrays are synthesized on standard-sized glass microscope slides, compatible with many microarray scanners. NimbleGen provides a comprehensive user's guide and offers a line of instruments, reagents kits and consumables to support customers with sample labeling, hybridization, scanning, data extraction, and analysis. Please contact Roche NimbleGen for a list of required equipment and reagents. NimbleGen also offers a training program to get you up and running with NimbleGen arrays quickly.

CGH/CNV Service Workflow

Customers can choose to access NimbleGen whole-genome and custom targeted array technology through NimbleGen's full service microarray processing facility. NimbleGen's CGH/CNV microarray service involves the following:

1. Customer selects a catalog whole-genome design or works with the NimbleGen bioinformatics team to create a custom array.
2. Customer ships sample(s) to the NimbleGen service lab.
3. NimbleGen manufactures the array and performs the hybridization and data analysis.
4. Roche NimbleGen ships the following deliverables in DVD format:
   • Array design files
   • Raw data
   • Normalized and processed data (using NimbleGen's segMNT v1.1 copy number analysis algorithm) in GFF, PDF, and TXT formats
   • Annotation GFF files
5. Customer views data using NimbleGen's SignalMap software and other standard software programs (e.g. Microsoft Excel, Adobe Acrobat).

Roche NimbleGen offers comprehensive data processing and analysis software tools for CGH/CNV analysis. Software available from NimbleGen includes:

• DEVA automates the feature extraction, primary data analysis, and visualization process for Roche NimbleGen CGH, CNV, and CGX arrays. Using Roche NimbleGen design files and scanned array images, DEVA software will automatically detect new scanned array images, process them, and run the analyses.
• Nexus Copy Number Standard simplifies CNV genetic aberration analysis with tools including custom annotation tracks, integration of custom databases (e.g. CNVs, genetic disorders), and segmentation algorithms.
• Nexus Copy Number Discovery includes all the same features as Copy Number Standard plus additional computational modules for advanced analysis.
• SignalMap Provides a simple and interactive data browsing tool to view and interpret CGH/CNV data in GFF format. A free, 30-day demo version of SignalMap software is available for download.

Brochures & Sales Flyers

• NEW! Roche NimbleGen Research Solutions: Microarrays and target enrichment for genetic disease discovery
  Brochure (PDF Format 7.1MB)
• NimbleGen CGH/CNV Microarrays
  Brochure (PDF Format 2.2MB)
• NimbleGen Human CGH Whole-Genome Arrays
  Brochure (PDF Format 2.2MB)
• NEW! NimbleGen CGH ISCA Plus Cytogenetic Arrays
  Sales Flyer (PDF Format 1.2MB)
• NEW! Nexus Copy Number Software for Cytogenetics
  Sales Flyer (PDF Format 1.4MB)
• NEW! NimbleGen CGH 4.2M Platform Arrays
  Sales Flyer (PDF Format 666KB)
• NEW! Nexus Copy Number Software for CGH Research
  Sales Flyer (PDF Format 1.1MB)
• NimbleGen Copy Number Variation (CNV) Arrays
  Sales Flyer (PDF Format 1.4MB)

User Guides

• NimbleGen Arrays User’s Guide: CGH Arrays & CGH/LOH Arrays (Version 9.0)
  User’s Guide (PDF Format 2.6MB)
• NimbleGen Arrays User’s Guide: CGX Arrays (Version 3.1)
  User’s Guide (PDF Format 3.7MB)

Downloads

• Descriptions of HG18 and HG19 Annotation Files (Version 3.0)
  Datasheet (PDF Format 409KB)
• Human Genome HG19 Annotation Files
  Annotation Files (ZIP Format 12.8MB)
  What files are included in this download?
• Human Genome HG18 Annotation Files
  Annotation Files (ZIP Format 11.2MB)
  What files are included in this download?

Application Notes, Technical Notes & Whitepapers

• Detecting Copy Number Variants Associated with Basal Cell Carcinoma in an Arsenic-Exposed Population
  Application Note (PDF Format 1.2MB)
• Array CGH using DNA from Formalin-Fixed Paraffin-Embedded (FFPE) Tissue Samples
  Technical Note (PDF Format 2MB)
• NEW! Metrics for Optimizing CGH/LOH Array Data Quality
  Technical Note (PDF Format 1.8MB)
• High Resolution Copy Number Analysis of Parkinson’s Samples Using Nexus Copy Number and Roche NimbleGen Microarrays
  Whitepaper (PDF Format 964KB)