Rare diseases: or, what happens when backups fail

Cat keyboard

A word with your data backup. ;;tewpitqg[[[nmcappoegapdgud. No? Thought so.

Ploidy is a funny old Greek word for a modern, almost modish concept: data backups. Ploidy is the number of copies of an organism’s DNA. Certain kinds of algae, for instance, don’t buy into backups; they’re haploid, and contain only a single copy of DNA. Plants, on the other hand, are polyploidal; paranoiacs of the genetic realm, they contain dozens, and sometimes hundreds of copies of DNA. Us, we’re in the middle: human beings are diploid, with each of our cells containing two copies of DNA, one from mom, the other from dad.

Two copies of anything is reassuring. This article is diploid: one copy glares at me from my screen, and the other scooches in a server somewhere on the cloud. And so when my cat, also diploid, walks across my keyboard, deleting most of my article and transmuting the rest into gibberish, my annoyance at her is mostly for show. Diploidy, it saves pet cats: who knew?

The similarity between cloud backups and diploidy in humans cuts deeper than jokes about cats, however. Much like data, all DNA is a communiqué, a myth that passes on from generation to generation. Mom and dad come together to write an epic. Mom heard a version of this epic from her parents; Dad heard a slightly different version from his. You—the stuff of you—is both epics, side by side. The 3 billion year hope is that these subtly different epics, coming together, help you thrive in your time, allowing you to craft bear-cleaving augers in the Iron Age or write a fun blog post in the Age of the Cloud.

Genetic diversity is a happy offshoot of diploidy; if DNA is an epic, its mishearings can be fruitful. Maybe dimpled chins run in your family. Your mom has one, and so does her mom before her. Say dimpled chins arise from a genetic mutation named D; the absence of this mutation is N, say. Then your mother’s genes in the bits of her DNA responsible for chins, dimpled or otherwise, might look like this:

Figure T: Your mom gets her movie-star chin from your grandma.

Figure T notates the two copies of DNA your mom carries with a pair of letters separated by a pipe. The letter to the left of the pipe is the gene from her mom, and the one to the right is from her dad. And so, in the case of dimpled chins, a single mishearing—a single mutated copy—is all your mom needs to be the perpetual envy of her generation, because—you got it—dimpled chins are exotic in this part of the world.

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Webinar on DNA-Seq data analysis- Case studies

DNA-Seq data can be analyzed and visualized using an extensive workflow in Strand NGS software. The software has been designed for the biologists. Strand NGS supports analysis of whole exome, whole genome and targeted sequencing experiments. The DNA-Seq workflow includes the ability to detect variants (SNPs, MNPs and short InDels), annotate them with dbSNP, and report for each SNP the kind of effect it has on the genes and provides list of affected genes. Biological contextualization of the affected genes can be performed by downstream analysis such as GO, GSA, pathway analysis. Continue Reading →

The clinical workflow, retinoblastoma and split alignment

 

An infant with leukocoria, a common retinoblastoma symptom visible in photographs taken with a camera flash. The normal right eye reflects red, as it should; the left eye, infected, reflects white.

 

Retinoblastoma is an “oma” named for its surface effect, its “presentation”:  it’s a cancer that attacks the eye. Worse, because 80% of retinoblastoma diagnoses occur before the age of 3, it’s a cancer that attacks the eyes—almost exclusively—of little children. Retinoblastoma is a “good cancer”: 90% of all RB cases survive into adulthood. But the fine print is terrifying: extensive radio or chemotherapy; a lost or severely circumscribed childhood; the possibility of losing vision in one or, in bilateral cases, both eyes.

India’s retinoblastoma numbers aren’t good. Year round, India diagnoses 20% of all RB cases in the world. Of these, between 10 and 30% go on to lead functioning lives as adults; the rest are disabled for life or die. Death from RB, let alone blindness, ought not to be a reality. But India’s masses, a majority of them rural, are mostly unaware of the disease; or, despite awareness, are usually diagnosed in the later, more devastating stages; or, despite early diagnosis, can’t afford treatment. Lack of knowledge, lack of means, lack of access: the trifecta is poisonous, and in a relentless condition like cancer, unsurprisingly lethal.

A genetic disease, retinoblastoma is caused by a change, or a mutation, to the genetic code. Genetic mutations come in three basic varieties: substitutions swap one base (or a stretch) for another; insertions add a base or a stretch of bases where none previously existed; and deletions remove bases. These categories are useful from a purely visual standpoint: but what really matters is their effect on the human body. For reasons that involve 3 billion years of trial and genetic error, our genetic codes are resistant to mischief.   Most mutations do not cause a loss of function; the average human carries about 4 million mutations, and only a handful of these may, over the course of his life, cause him harm.

However, like most cancerous mutations, the one in retinoblastoma isn’t just harmful: it’s positively disfiguring. Retinoblastoma is caused by a deletion, the removal of a contiguous stretch of bases (Figure D).

Figure D: A 4 base deletion. Bases 4 through 7 from the reference are deleted.

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Webinar on RNA-Seq Data Analysis

Strand NGS supports an extensive workflow for the analysis and visualization of RNA-Seq data. The workflow includes Transcriptome / Genome alignment, Differential expression analysis with Statistical approach and Splicing events detection. Strand NGS also supports novel discovery like identification of novel genes, exons and Novel splice junctions, alongside it can also detect gene fusion events. Further downstream analysis such as GO and pathway analysis can be performed on the set of interesting genes. The product has an option to create pipelines for time consuming jobs which automates analysis and leaves more time for end data interpretation. This webinar will give an overview of the features in the RNA-Seq data analysis workflow in Strand NGS and also highlights on parameters within each feature that can be optimized depending on datasets and analysis needs. Continue Reading →

Webinar on Implications of Next Generation Sequencing in Molecular Diagnosis of Cancer

Genetic testing requires screening of the entire gene, which by conventional sequencing is time consuming and expensive. Next Generation Sequencing (NGS) based approaches increase the sensitivity of mutation detection, making it fast and cost-effective compared to the conventional tests performed in a reflex-testing mode. Strand NGS includes workflows with quality assessment and filter sections that do not require any manual intervention. Post-analytical workflows in Strand NGS allow users to execute sequence analysis with stringent filtering to eliminate false positive and low quality reads. This simplifies the analysis in large scale cohort settings, where every sample needs to be processed identically.

In this webinar we will discuss the implications of next generation sequencing based tests in multi-gene testing. We will also show how NGS based tests help to identify copy number variations, split read analysis and breakpoint identification. Finally, we will show a brief glimpse of Indian cohort data, where NGS based tests have shown improved mutation detection. In this webinar, we will present clinical case studies in on Hereditary Breast and Ovarian Cancer (HBOC) and Retinoblastoma patients to demonstrate how CNV analysis in Strand NGS enables researchers to detect and visualize copy number changes ranging from single exon to full gene. Continue Reading →

Celebrating 25th Release announcement of Strand NGS

We are happy to share the announcement of the 25th release of Strand NGS (v2.8). We started our journey as bioinformatics experts in 2000, and moved into the next-generation sequencing space with the launch of Strand NGS (formerly Avadis NGS) in October 2010. Since then we have grown with our customers, added more workflows, features, enhancements and improvements to the tool. Our technical support, experienced application scientists and R&D team have continuously strived to provide the best tools and support to all our customers. We thank you for being with us in this journey and look forward to your continued support.

We hope you love all the features in Strand NGS! If you are working on one of those organisms with particularly large genomes that we have not supported until now, or were waiting for alignment of circular genomes, please do not hesitate to get in touch. We’d love to show you what Strand NGS can do for your research!

You can access release notes here or visit website

Reduce the SNP annotation time by up to 95%

Explore the new script ‘Create Targeted VAL’ in Strand NGS for creating subset of dbSNP database with target regions of interest and run your analysis. This feature reduces your SNP annotation time by up to 95% depending on the target regions of interest.
Strand NGS v2.7 has more exciting features. Listed below are few: Continue Reading →

Strand NGS v2.7 released

We are excited to share the release of Strand NGS v2.7. This new version comes with several exciting features and enhancements. Listed below are few major enhancements: Continue Reading →

Review of selected publications citing Strand NGS

In 2015, we brought in many new features and improvements based on your requirements and feedback. We expanded the Strand NGS epigenomics toolkit by adding the MeDIP-Seq workflow in the v2.5 release. We also added new features like the alignment workflow and SV detection for split reads (watch the webinar), a browser-based copy number variation (CNV) view (watch the webinar), and correlation analysis. 2015 was also a year with some great publications that cited Avadis NGS and Strand NGS. Here is a small selection:

K-bZIP Mediated SUMO-2/3 Specific Modification on the KSHV Genome Negatively Regulates Lytic Gene Expression and Viral Reactivation (Wan-Shan Yang, et al.) published in PLoS Pathogens. The authors looked at ChIP-Seq data as well as RNA-Seq data to study the association of SUMO paralog genome modifications with KSHV (one of the seven known human oncoviruses) reactivation. Avadis NGS was used to align ChIP-Seq data to the KSHV genome build and to delineate the SUMO-1 and SUMO-2/3 binding patterns. RNA-Seq reads that did not align with hg19 were mapped with the KSHV genome in Avadis NGS and differential gene expression was determined based on sample wise transcript RPKM values reported by Avadis NGS and verified by RT-qPCR. Continue Reading →

Webinar on Strand NGS Pipeline Manager for streamlining large scale analysis

This webinar, will highlight the Strand NGS Pipeline Manager feature. In this webinar, you will learn how to customize pipelines and share them with other Strand NGS users. This webinar will give a brief glimpse of an elaborate pipeline that aligns reads, filters poor-quality matches, computes coverage metrics, identifies variants, checks for sample cross-contamination, and emails quality reports – all from within Strand NGS. Vamsi will also be available for live questions at the event.

Speaker: Dr. Vamsi Veeramachaneni, Vice President – Bioinformatics, Strand Life Sciences

Details:
Session 1: 02:30 PM IST; 24 Feb 2016
Session 2: 10:30 PM IST; 24 Feb 2016

Register at http://www.strand-ngs.com/webinar_registration

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