Archive by Author

Breaking the Human Genome Code

On one hand side we are able to sequence anyone’s genome cheaply and quickly due to latest technologies. On the other hand side we are at the beginning to discover the true meaning of individual genomes. This is the reason why the lecture has the subline “Opening Pandora’s Box”.

Professor Winston Hide talks about newly arising questions such as:

  • If you have your genome sequenced, who should see it?
  • How can we safely share a genome without ending up opening a whole new form of cybersnooping?
  • How could the new technologies be used to predict a person’s predisposition for Alzheimer’s, Parkinson’s or motor neurone disease?

Sorry, No Identical Genomes

We asked you about the findings that identical twins do not have identical genomes. Find the results here:

identical_twins

Has the time come for validated NGS panels?

Clinical validation** Challenges of validating next generation sequencing panels ** Advantages and disadvantages of FDA-cleared products **

Most of us endorse that NGS can and should be used as part of clinical molecular diagnostic testing menus. On the other hand side developers of next generation sequencing-based assays agree that there are still significant challenges in developing clinical NGS-based gene panels – from the sequencing technology itself to differences in laboratories’ bioinformatics pipelines, DNA extraction and sample prep protocols, as well as differences in the sample itself.

Please keep apart: assay development and validation

It is important to note that the assay development process should be separated from the validation process:

  • Generation of a protocol for the whole diagnostic test is the main focus of the assay development.
  • The downstream process is important to validate sequencing-based clinical assays. Maybe you are interested in the CAP checklist for NGS in clinical labs.

Researchers should keep in mind that some of the main challenges of assay development and validation have nothing to do with the sequencing itself.

Pros and cons of FDA-cleared products
Pro Contra
  • FDA-cleared in vitro diagnostic tests could resolve some of the issues of developing and validating LDTs
  • No development and validation costs for the lab (Instead, they must verify that the assay performs according to the FDA label)
  • Expensive compared with LTD
  • Dependency on the vendors for trusting their validation and that they will be able to supply reagents
Accounting exercise for cleared products vs. LDTs

Currently, the only FDA-cleared NGS-based tests are Illumina’s 2 cystic fibrosis assays that run on its MiSeqDx system.

A 139-variant assay kit for example has a list price of approx. €6,800 including two runs on the MiSeqDx. Up to 45 patient samples can be multiplexed per run, which could cost €80 per patient.

It is an impressive difference if it is compared with a cystic fibrosis LDT that can be run for less than €45 per patient excluding development and validation costs.

Even more expensive is the full-gene assay by Illumina with a list price of approx. €56,000 including six runs and the ability to multiplex between six to eight patients per run meaning €1,600 per patient. Just keep in mind that costs could soar to €9,500 per patient, compared to an LDT that could sequence the entire CFTR gene for €180.

 

Let’s see what time will bring. There are many aspects that need to be discussed regarding labs’ ability to tweak tests or to combine elements of different technologies and protocols to solve problems.

______________________________________________________________

What about you? Are you using panels or homebrew protocols for your NGS projects, like exome sequencing or cancer testing? Just participate in our poll.

Highlights: Advances in Genome Biology and Technology 2015 (AGBT)

NewsLast week the 16th annual Advances in Genome Biology and Technology (AGBT) meeting was held in Florida (USA). The meeting is important to the genomics research community because it provides an dialog forum for the latest advances in DNA sequencing technologies, experimental and analytical approaches for genomic studies and their myriad applications.

The 2015 meeting featured clinical translation of next generation DNA sequencing technologies and pipelines. Find here our best catches:

  • 10X Genomics: GemCode platform lauched. It allows users to obtain long-range genomic information from placing short sequence reads in the context of large DNA fragments. Its applications include haplotype phasing, structural variation analysis and de novo genome assembly. We will see how GemCode will “change the definition of sequencing“.
  • Illumina: New details on newly launched NeoPrep. The system automatically prepares DNA or RNA samples for sequencing on Illumina instruments. In addition to library creation, NeoPrep performs a few quality control checks, quantifying the DNA molecules to be sequenced and normalizing libraries for even coverage during sequencing.
  • PacBio: Whole genome sequencing with high quality assemblies. Get some application cases on GenomeWeb.
  • Kapa Biosystems: Library preparation products for next generation sequencing (NGS) DNA and RNA analysis launched.

Assessment of NGS Tools for Crime Laboratories

protocolUS Researchers has been awarded with $825,000 to evaluate the use of NGS technology for forensic applications.

Pennsylvania State University will work in conjunction with the Battelle Memorial Institute, the lead institution on the grant, and 6 other laboratories. As the sole university partner, Penn State will be performing evaluations of forensic investigative tools that will expand the capabilities of forensic DNA laboratories.

The grant will test the feasibility of new instruments, laboratory materials and software tools in the field of DNA-based forensics. The study’s aim is to vet tools using next generation sequencing technology and implement them into working crime laboratories.

According to the grant abstract, DNA samples are provided by the National Institute of Standards and Technology. They will be sequenced using Illumina’s MiSeq platform or Life Technologies’ Ion PGM Sequencing System.

The laboratories hope to be able to get tools that use NGS into working crime laboratories to replace current less-informative forensic methods. The new technology will increase efficiency in forensic work and could also help generate investigative leads and identify individuals with only traces of genetic evidence.

Visit forensics.psu.edu/research for more information about the Department of Forensic Science at Pennsylvania State University.

Whole Genome Sequences Of World’s Oldest Living People Published

senior-asian-woman-100226669Researchers looked at the genome of some of the oldest living people. While they did not find a significant association with extreme longevity, the researchers published their genome findings. At least the data will be available as a resource for future researchers looking at the “genetic basis” of longevity.

There are 74 supercentenarians (110 years or older) alive worldwide, with 22 living in the United States. The authors of this study performed whole genome sequencing on 17 of them to explore the genetic basis underlying extreme human longevity.

“We were looking for a really simple explanation in a single gene,” said Stuart K. Kim, a Stanford geneticist and molecular biologist. “And we know now that it’s a lot more complicated, and it will take a lot more experiments and a lot more data from the genes of more supercentenarians to find out just what might account for their ages.”

From the limited sample size the researchers were not able to find protein-altering variants associated with extreme longevity, according to a study in PLOS ONE by Hinco Gierman from Stanford University and colleagues published November 12, 2014 . But they did find one supercentarian had a genetic variant related to a heart condition that had very little effect on his health considering he reached such and elderly age. The researchers noted that it is recommended by the American College of Medical Genetics and Genomics to report this instance as an incidental finding.

The whole genome sequences of all 17 supercentenarians are now available as a public resource so that they can be used to assist the discovery of the genetic basis of extreme longevity in future studies.

 

Compare to Large genome sequencing studies in the USA (posted August 26, 2014 )

Are you ready to have your genome sequenced?

Genome sequencingLast month we asked if you would be interested in sequencing your genome. If the costs would be lower, the majority said “YES”.

More than 20% answered that their genome has already been sequenced. Personally, I would be very interested to know what they did with the data output.

 

If you are one of the guys who voted “I already have” please submit a comment why you decided to have your genome sequenced.

The future of miRNA analysis

We asked you in which technology you see the future of miRNA analysis.
Find here the voting of the 102 participants:

miRNA