Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

California computer scientists double volume of data in NIH biotech repository

27.10.2005


Faster Computation of Haplotypes Provides Insight into Genetic Basis of Human Disease



High-throughput sequencing of an individual’s DNA yields a map of genetic variation which can give clues to the genetic underpinning of human disease. The current technologies collect genotypes, or information from the individual’s two chromosomes. Yet many scientists believe that drilling down to the variations between individuals’ DNA at the level of each chromosome -- so-called haplotypes -- will permit more accurate study of genetic differences and their consequences for medical research and the study of evolution.

Experimental methods for deriving these haplotypes are expensive and time-consuming. But now experts in bioinformatics at two California research institutes have used a different, very fast and relatively low-cost computational tool to ’crunch’ the world’s largest repository of genotypes to predict their haplotypes -- and they did so in less than 24 hours, approximately 1,000 times faster than the prevailing technology until now. Their findings are featured in a special issue of the journal Genome Research, published today.


"This information provides an invaluable resource for understanding the structure of human genetic variation," said lead author Eleazar Eskin, a professor of computer science and engineering at the University of California, San Diego who is affiliated with the California Institute for Telecommunications and Information Technology (Calit2). "A deeper understanding of the data will improve the design of studies that look for associations between certain genes and disease or inherited conditions."

The team from UCSD and the International Computer Science Institute (ICSI) processed all 286 million human genotypes in the dbSNP database of the National Center for Biotechnology Information (NCBI), part of National Institute of Health’s National Library of Medicine. The repository includes all publicly available data on single nucleotide polymorphisms (SNPs), which are sites in the DNA sequence where individuals differ at the level of nucleotides.

These SNPs (pronounced snips) are locations in the human DNA sequence where two possible bases occur in the population. SNPs account for the most common type of variation in DNA sequence in humans and due to the recently developed high-throughput genotyping technology, genotype information on an individual’s SNPs can be collected very cheaply.

Enter computational biologists around the world who have been devising ways to infer or extrapolate these haplotypes from the flood of genotype data produced by DNA sequencing efforts. Eskin and Ph.D. candidates Noah Zaitlen and Hyun Min Kang at UCSD, and research scientist Eran Halperin at ICSI, worked with NCBI scientists Michael Feolo and Stephen Sherry to infer haplotypes based on all of the data from genotyping studies deposited in NCBI’s dbSNP database. Rather than use standard methods for inferring haplotypes, the computer scientists used HAP, a software tool originally developed at ICSI by Halperin and Richard Karp in collaboration with Eskin.

They ran the HAP algorithm on all dbSNP data sets using a cluster of 30 Intel Xeon processors provided by Calit2’s National Science Foundation-funded OptIPuter project, in cooperation with the National Biomedical Computation Resource. Both organizations are based at UCSD. "In under 24 hours we were able to process more than 286 million haplotypes, partition those haplotypes into blocks, or regions, of limited diversity, and determine a set of ’tag’ SNPs that capture the majority of genetic variation," explained Halperin.

The researchers’ article appears in a special issue of Genome Research on "Human Genetic Variation," and its publication coincides with the release of a wide-ranging genotype study by the International HapMap Consortium in the journal Nature. The group’s HapMap is a map of haplotype blocks and the tag SNPs that identify the haplotypes from a database of 160 million genotypes of 270 individuals from four different populations with ancestors from parts of Africa, Asia and Europe. The HapMap data is a major resource for understanding the structure of human variation and the genetic basis of human disease.

All of the HapMap data is deposited in NCBI and was made available to the California researchers for their computation, along with more than a dozen other data sets, including the second-largest behind HapMap: 110 million genotypes published earlier this year by a consortium led by Perlegen Sciences.

"The speed with which we are able to compute the entire dbSNP database of genotypes is a combination of the speed of our algorithm and the computational resources that allowed us to do it so quickly," explained Eskin, a professor in UCSD’s Jacobs School of Engineering. "We have demonstrated that haplotype phasing can be done routinely every time there is a new release of data deposited in the NCBI database."

"By reducing the waiting time to just 24 hours, NCBI can make it an integral part of the build cycle for dbSNP," said NCBI’s Stephen Sherry. "Every time there is a new release of polymorphism and human variation information in our database, our colleagues in California will be able to re-compute the haplotypes and tag SNPs." To underscore that point, in early October the researchers ran another complete computation on an updated version of the NCBI database that has not yet been made public.

ICSI’s Halperin notes that working with the entire dbSNP database showed that HAP works well on diverse data sets. "The challenge of analyzing such a large dataset is enormous, since the integration of the different datasets is not a simple task," explained the research scientist. "In particular, different data sets have different characteristics, and one has to take this into account. This project demonstrates the ability of HAP to efficiently deal with different types of data, for instance, unrelated or related individuals." Indeed, for the project, Halperin extended the HAP algorithm to work with ’trios’ -- where genotypes are available for a mother, father and their child -- taking into account that haplotypes of the children are copies of the haplotypes of the parents.

As a side effect of their research, the computer scientists are now depositing 15 gigabytes of data into dbSNP, and their article in Genome Research aims to encourage the research community to use the data depository as a scientific resource. Researchers can use these reference data sets as tools to guide their own studies into the genetic basis of common diseases.

To that end, the team’s next collaboration with NCBI researchers will be to help design disease-association studies. "If a researcher is interested in a specific gene, we can use all the available data to come up with how to design the experiment," said Eskin. "We can tell how many individuals’ genotypes need to be sequenced - and how many and which SNPs to collect - to minimize the cost and processing power needed for the most effective study correlating genetic data and the incidence of disease."

Disease association research is the main reason why the group from Calit2 and ICSI opted to identify tag SNPs across the entire NCBI database and make all of them available to the research community. Said Halperin: "If you are going to perform a disease association study, it’s more economical to use these tag SNPs than the entire data."

Doug Ramsey | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>