Copy number analysis
Copy number analysis usually refers to the process of analyzing data produced by a test for DNA copy number variation in patient's sample. Such analysis helps detect chromosomal copy number variation that may cause or may increase risks of various critical disorders.[1] [2] Copy number variation can be detected with various types of tests such as fluorescent in situ hybridization, comparative genomic hybridization and with high-resolution array-based tests based on array comparative genomic hybridization (or aCGH) and SNP array technologies. Array-based methods have been accepted as the most efficient in terms of their resolution and high-throughput nature[3] and they are also referred to as Virtual Karyotype. Data analysis for an array-based DNA copy number test can be very challenging though due to very high volume of data that come out of an array platform.
BAC (Bacterial Artificial Chromosome) arrays were historically the first microarray platform to be used for DNA copy number analysis. This platform is used to identify gross deletions or amplifications in DNA. Such anomalies for example are common in cancer and can be used for diagnosis of many developmental disorders. Data produced by such platforms are usually low to medium resolution in terms of genome coverage. Usually, log-ratio measurements are produced by this technology to represent deviation of patient's copy number state from normal. Such measurements then are studied and those that significantly differ from zero value are announced to represent a part of a chromosome with an anomaly (an abnormal copy number state). Positive log-ratios indicate a region of DNA copy number gain and negative log-ratio values mark a region of DNA copy number loss. Even a single data point can be declared an indication of a copy number gain or a copy number loss in BAC arrays.
Copy Number Analysis Software
Nexus Copy Number
Handles data from most technologies and manufacturers. Allows concurrent analysis of and comparison between different platforms, and integrates different data modalities (copy number, sequence variants, and gene expression). The user-interface allows detection of structural variations (e.g. copy number, homozygous regions), association with sequence variations (point mutations, InDels, inversions, etc.), and identification of statistically significant co-occurring up/down regulated genes (from mRNA, miRNA, and RNASeq data). Version8.0 was released in early 2016 that allows users without bioinformatic expertise to easily import BAM files to be able to visualize and analyze copy number as well as LOH and allelic Imbalance events. [4]
Nexus Copy Number is also integrated with TCGA Premier, which is a resource that contains 12,000 tumors across more than thirty cancer types. This allows users to quickly query the database, retrieve samples of interest along with annotations, and further analyze the data sets. [5]
See also
References
- ^ Sebat, J.; et al. (2007). "Strong association of de novo copy number mutations with autism". Science. 316 (5823): 445–9. doi:10.1126/science.1138659. PMC 2993504. PMID 17363630.
- ^ St Clair D (2008). "Copy number variation and schizophrenia". Schizophr Bull. 35 (1): 9–12. doi:10.1093/schbul/sbn147. PMC 2643970. PMID 18990708.
- ^ Bassem A. Bejjani and Lisa G. Shaffer (2006). "Application of Array-Based Comparative Genomic Hybridization to Clinical Diagnostics". J Mol Diagn. 8 (5): 528–33. doi:10.2353/jmoldx.2006.060029. PMC 1876176. PMID 17065418.
- ^ "BioDiscovery releases Nexus Copy Number 8.0 with cutting-edge features: estimation of copy number and allelic events from NGS data". BioDiscovery, Inc. March 17, 2016. Retrieved April 6, 2016.
- ^ "TCGA Premier". TCGA Premier. BioDiscovery, Inc. Retrieved April 6, 2016.