BioDiscovery
Diploid Recentering: When, Why and How
March 21st, 2013
It is well established that cancer frequently undergoes copy number changes, which is why copy number is frequently evaluated in cancer samples for diagnostic and research purposes. However, when beginning copy number analysis of a sample using a SNP array, it is important to run a quick sanity check to validate that the baseline calling is in fact calling diploid regions. In simple terms: Are the “normal” areas normal? SNP arrays give information for both copy number and b-allele frequency. With most copy number analysis, median recentering is selected by default. This is appropriate when a sample is close to diploid. Read More
How to Identify Chromothripsis in Tumor Samples
February 13th, 2013
Chromothripsis, or chromosomal shattering, occurs at a frequency of 1%-5% in most cancer types, though has been described as being upwards of 25% in bone cancer (Cell. 2011 Jan 7;144(1):9-10). It has been associated with poor prognosis (Cancer Res. 2012 Dec 27). Chromothripsis has even been found to occur in the germline of some developmental disorders (Hum Mol Genet. 2011 May 15;20(10):1916-24, Cell Rep. 2012 Jun 28;1(6):648-55.). This complex chromosomal rearrangement is thought to occur when the chromosome breaks apart into tens or even hundreds of pieces and is then rejoined through nonhomologous end-joining. While a primary indicator of chromothripsisRead More
Evaluating sequencing methods against microarrays for copy number analysis
February 12th, 2013
Sequencing is increasing in popularity as a platform for copy number analysis. But how does it stack up to traditional methods (typically microarrays) ? To answer this, or at least begin to, the question has to be reframed around “which” array technology is being compared to “which” sequencing methods, what the scientific goals are (broadly, and as relates to copy number analysis), and, equally important, the nature of the samples. Looking at a recent paper (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919738/), cost-effective sequencing techniques can be used to detect large copy number changes. The low-depth techniques have low resolution (e.g., in the paper 0.04x coverage resolvedRead More
Genome annotations - now on the Downloads page!
February 7th, 2013
Did you know that you can use data from virtually any genome to identify copy number variations (CNV) and LOH using Nexus Copy Number and Nexus Solo? When you first launch the software and create a new project, you will see two organisms (human and mouse) in the “Organism” dropdown. But you are not limited to these two organisms. These two are included with the installer as they are the most commonly used and we want to keep the installers as small as possible. But you can easily add a new organism if you don’t work on human or mouseRead More
Estimation of Aberrant Cell Percentage in Tumor Normal Cell Mixture
February 5th, 2013
Cancer samples, especially solid tumors, usually contain a mixture of tumor and normal cells. Using both the SNP and copy number information provided by SNP arrays (Affymetrix or Illumina), the % aberrant cells can be estimated. Here we are going to discuss a simple formula for such calculation based on one-copy loss event. Figure below shows the B-Allele Frequency (BAF) bands in a region where a mixture of aberrant cells with one-copy loss and non-aberrant/normal cells is present. With no aberrant cells (0%), or only normal cells, a typical 3-band BAF pattern is displayed on the left, indicating AA (0% BAF), ABRead More
Paired Analysis
February 1st, 2013
Copy number variants (CNVs) are recognised to be part of the natural genetic variation in humans. Although there is still work to do to fully understand biology involved, it is likely that CNVs are responsible for a considerable proportion of phenotypic variation between individuals. On the other hand, copy number alterations (CNAs) are somatic changes in copy number that are characteristic of the genome of cancerous cells. These CNAs can affect cancer genes such as tumor suppressor genes and oncogenes. Both somatic copy number alterations (CNAs) and germline copy number variants (CNVs) that are prevalent in healthy individuals canRead More
How to analyze NGS data in Nexus
January 15th, 2013
This post deals with loading NGS data into Nexus for copy number variation and structural variants. BAM files produced from NGS have to be processed before loading into Nexus. Variant calls in VCF format can be loaded into the next version of Nexus to be released shortly. VCF files can be created from BAM files with tools like GATK Or VarScan Or samtools mpileup option. For Exome data, where matching sample and reference BAM files are present, Dr Sean Davis’ Python script ngCGH can be used to create a text file (with log2ratio of read-depth counts) and loaded into Nexus with NGS custom dataRead More
PAG XXI starts in a few days!
January 9th, 2013
The annual Plant and Animal Genome Sciences (PAG XXI) meeting is starting this weekend in San Diego, CA. This is the largest genomics conference focusing on non-human species and attendance is expected at over 2800. BioDiscovery will be exhibiting at booth #407 so stop by and talk to our application specialists on how our products can help you with your agricultural genomics projects. We have products for copy number variation analysis from microarray and NGS technologies and for mRNA/miRNA expression analysis. Our products support research on any organism for which genome data is available. We have customers working on organismsRead More
From Raw Data to Copy Number Calls - Data processing workflow in Nexus Copy Number
December 27th, 2012
The so-called “Raw Data” for the data analysis in Nexus Copy Number can be intensity values for array probes (Affymetrix CEL files), logRatios after normalization (Agilent Feature Extraction results files and Illumina final report files), or even copy number state values (Affymetrix OncoScan data). Let’s take a look at how Nexus Copy Number handles the different “Raw Data” and what is common in the overall data processing workflow. Affymetrix CEL files (intensity values) need to be normalized to generate logRatios before proceeding to copy number analysis. A normal reference file generated from the HapMap pooled samples is used for this purpose. Read More
Need software but don’t have the funds?
December 19th, 2012
'Tis the season of giving and BioDiscovery shares that sentiment! We have recently launched a software donation program to benefit pediatric research. It is heartbreaking to see young ones struggle with illness and not be able to share in the same joys of childhood as their peers. The scientific community has made a lot of progress in finding new treatments as well as creating methods for earlier diagnosis. Often though, funding becomes a barrier and great ideas or projects aren’t able to germinate. Dr. Soheil Shams, President of BioDiscovery, said it well when he stated “Limitations on funding should notRead More
Review of "Statistical Challenges associated with detecting copy number variations with next-generation sequencing"
December 18th, 2012
With the deluge of data streaming from Next Generation Sequencing (NGS) technologies, scientists are scrambling to find the best methods for Copy Number Variation (CNV) analysis. Of the two main types of NGS data used for CNV analysis – Whole Genome and Exome sequencing, the paper “Statistical Challenges associated with detecting copy number variations with next-generation sequencing” (Bioinformatics. 2012 Nov 1;28(21):2711-8.), reviews germ-line Whole Genome Sequencing (not tumors) data analysis for CNVs and focuses principally on Depth of Coverage (DoC) methods. Next Generation Sequencing reads vary in length from 40 - 500 bp. Read files (eg. Fastq format) are mapped toRead More
ASH is here!
December 7th, 2012
The American Society for Hematology (ASH) Meeting officially starts tomorrow. Approximately 20,000 people will be attending this meeting at the Georgia World Congress Center in Atlanta, GA. With over 4300 oral and poster presentations, it is a daunting task to decide what to view. If you are looking at copy number variation or are considering doing this in the future and would like to see how BioDiscovery Nexus Copy Number enabled advances in your colleagues' research, let me point you to a couple of presentations. On Monday at 7:00 AM (B206, Level 2, Building B), Karen Rabin of Baylor College ofRead More
How to transition your project from one NCBI build to another?
December 3rd, 2012
It has been over 3 years since NCBI Build 37(hg19) has been released and your lab may want to move your data to this build. Perhaps you are getting new microarray or NGS data that is on the newest build and you want to include your legacy data in the same project. While this can be done in Nexus Copy Number, some platforms are more amenable to this transition than others. Affymetrix Affymetrix CEL files don’t require any work to load into the same project and can be loaded directly into the project of choice. This is because the genomic build positionsRead More
BioDiscovery is a proud sponsor of the Rare Disease Challenge
November 21st, 2012
The designation “rare disease” in the US is typically defined as having a prevalence of fewer than 200,000 affected individuals [1]. Considering that there are over 7000 diseases having this designation collectively affecting about 25 million Americans [1], it doesn’t seem so rare after all. A majority of these rare diseases are genetic in origin [1] and as BioDiscovery offers software and services that help identify genomic aberrations, we could not turn down an opportunity to help researchers make advances in diagnosis and therapy of such diseases. BioDiscovery is proud to be a Gold sponsor of the Rare Disease Challenge establishedRead More
2012 ASHG Lunch CNV Workshop - What's on the agenda?
October 31st, 2012
We hope you will join us at our CNV workshop at the 2012 ASHG Annual Meeting in San Francisco (details below). If you cannot make it to the workshop, please do visit us at Booth #813 for some Nexus fun - see the latest in BioDiscovery Nexus software and enter a drawing for an Android Nexus 7 tablet! We had a tremendous turnout for our lunchtime workshop at last year’s ICHG/ASHG meeting. This year we are privileged to have three great speakers who are going to share what they have been doing in CNV analysis. Dr. Shashikant Kulkarni from the Washington UniversityRead More
TCGA Level 3 Data is Now Available in Nexus DB
October 25th, 2012
The Cancer Genome Atlas (TCGA) has a multitude of publicly available genomic data that researchers can use in their own projects. Level 3 (segmented/interpreted) copy number data from TCGA is now available in Nexus DB. You can query this data from Nexus Copy Number or Nexus Solo and view and download all or selected samples from the query results. Once downloaded and added to your project, you can easily perform downstream analysis such as comparing between groups and identifying common aberrations. The data is organized into projects by disease (e.g. TCGA Thyroid Carcinoma Level 3 (segmented)) and you can alsoRead More
GC Wave Correction – when to use it, how and why
October 16th, 2012
Several customers have asked about when and whether to use GC wave correction. What causes waviness? Should a correction be applied even if there is no observable data waviness? Should I use a linear, quadratic, or lowess correction? GC waviness in the intensity signal (LogR) is dependent on the amount of input DNA and the GC content in the analyzed region. Although the precise mechanism is not fully understood, the change in signal can reduce a platform’s ability to detect copy number variants (CNVs). Although GC content introduces a bias in the sample, this can be subtracted (corrected) using a wave-correction fileRead More
Autism data from Autism Genetic Resource Exchange is now available via NexusDB.
October 16th, 2012
The Autism Genetic Resource Exchange (AGRE) consortium has been collecting samples and clinical data from subjects with autism spectrum disorder and their family members for over 15 years. The information available here has been invaluable to numerous researchers but retrieving copy number information from this data is not the easiest task, until now. The copy number data and some of the phenotype factors associated with these subjects are being made available through BioDiscovery NexusDB for exploration by consortium members. Anyone with access to Nexus Copy Number or Nexus Solo and a Nexus DB account can query/search the AGRE data in NexusRead More
How to obtain the number of tests performed for multiple testing when using the Comparisons tool in Nexus Copy Number
August 8th, 2012
The Comparisons feature in Nexus Copy Number uses a two-tailed Fisher’s Exact test. Instead of using the p-value, one can use the Q-bound value which corrects for multiple testing using the Benjamini-Hochberg FDR correction (Benjamini & Hochberg). If you want to know the number of tests performed for FDR correction when doing a comparison, there is a little trick that you can use in Nexus to obtain the number of tests. The number of tests for FDR correction is the number of regions where the aggregate changes. You can see all of the regions if you set the p-value threshold toRead More
Traditional methodologies are not optimal with genomic data analysis
July 23rd, 2012
Often in scientific discovery, the “division of labor” model allowing compartmentalization of different parts of a broader project is not the optimal solution. Some people don’t realize this until too much effort has already been put into a project or some are just not aware that a different approach is possible. The traditional approach in genomic data analysis often involves one group performing the wet lab work e.g. array hybridization and scanning and another group, the bioinformaticians/statisticians, performing data analysis. The latter group is often backlogged and cannot deliver results quickly and also usually does not possess detailed knowledge ofRead More
ISCA database CNV tracks are available in Nexus Copy Number and Nexus Solo
February 28th, 2012
Were you aware that the ISCA database CNV tracks can easily be loaded and viewed in Nexus Copy Number and Nexus Solo? The ISCA database contains whole genome array data from a subset of the ISCA Consortium clinical diagnostic laboratories. CNV calls and their clinical interpretations are available to the public and this great resource can be viewed easily in the Nexus genome browser. You just need to download the BED files from the ISCA website and load them into Nexus Copy Number/Nexus Solo. You then select to view these in the annotation tracks. The process is very easy and detailedRead More
BioDiscovery at the ISCO 2012 Congress,March 4-8 Mallorca, Spain
February 28th, 2012
Are you one of the lucky ones heading over to beautiful Mallorca, Spain at the beginning of March? ISCO 2012 Congress is a joint meeting with the European Workshop on Cytogenetics and Molecular Genetics of Solid Tumors in Mallorca, Spain from March 4-8. BioDiscovery will be presenting a talk on Tuesday, March 6, 13:10 – 13:50 in the Greco room at the meeting venue, Gran Meliá Victoria Convention Center. Please make sure to join us to hear about Integrated Genomic Analysis of an Ovarian Cancer Data Set. We are looking forward to catching up with customers and colleagues on the latest in cancer cytogenetics.Read More
