Category Archives: Genome

Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript. In order to enable it, please see these instructions. 13 hours ago Two new mathematically based algorithms for analyzing genomic data are not only more accurate and robust than their predecessors, but also allow integration of data from different sources. Credit: iStockphoto/Thinkstock

Researchers in Singapore have developed and tested mathematical tools, or algorithms, that are more accurate and robust than those currently used in analyzing high-throughput genetic sequencing data. The algorithms can determine the location and activity of specific nucleic acid sequences in a broad range of high-throughput techniques that detect geneprotein interactions. The research group, led by Shyam Prabhakar of the A*STAR Genome Institute of Singapore, also showed they could use the algorithms to generate meaningful results from degraded tissue and tissue constructed from several different cell types.

The rapid expansion in the application of high-throughput sequencing was possible because of a parallel growth in bioinformatics techniques to analyze the huge amount of data that the technique generated. High-throughput sequencing began as a technology for rapidly sequencing whole genomes; now it can detect gene activity, DNA methylation, microRNA binding and interactions between genes, transcription factors and regulatory elements. Each of these different sequencing techniques spawned its own specialized analytical methods, many of them based on heuristicspractical strategies that work but may require optimization.

Prabhakar and his colleagues recognized that almost all sequencing analyses are concerned with solving two major classes of problems, long studied in the fields of signal processingsignal detection and signal strength estimation. Standard mathematical techniques already existed for solving such problems. The researchers therefore adapted these techniques to sequencing analyses. They reasoned that the formal mathematical basis underlying the techniques would allow them to be optimized or tuned. They also realized that the same approaches could be used across a broad range of applications, thus enabling data integration.

The researchers developed two algorithms: DFilter for detecting and locating the binding of regulatory proteins to the genome; and EFilter for estimating gene activity through levels of messenger RNA, the genetic material used as a template for building proteins. Across several sequencing technologies, the researchers benchmarked both algorithms against existing analytical methods. They found that DFilter and EFilter outperformed the more specialized algorithms. The new algorithms also facilitated the analysis and comparison of multiple and diverse data sets.

Prabhakar and co-workers also used their new algorithms to analyze data from complex, heterogeneous tissue in the embryonic mouse forebrain. They searched for functioning transcription factors and gained useful insights, despite the fact that individual transcription factors could not be assigned to specific cell types.

"We intend to make DFilter and EFilter widely available," says Prabhakar, "perhaps via cloud genomics providers, if all goes according to plan."

Explore further: Scientists cut through data noise of high-throughput DNA sequencing with mathematical technique

More information: Kumar, V., et al. Uniform, optimal signal processing of mapped deep-sequencing data, Nature Biotechnology 31, 615622 (2013). http://www.nature.com/nbt/journal/v31/n7/full/nbt.2596.html

(Phys.org) Scientists at A*STAR's Genome Institute of Singapore (GIS) have developed a revolutionary method to quickly cut through noise and generate a unified and simplified analysis of high-throughput biological data ...

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Formal mathematics underpins new approach that standardizes analysis of genome information

Dr. Daoud Meerzaman: Computational Tools for Cancer Genome Analysis
On July 24, 2013, NCI #39;s Dr. Daoud Meerzaman, Director of R D/Section Head of Computational Genomics Research (CGR) at the Center for Biomedical Informatics a...

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Mouse Genome Informatics (MGI)
Presented by Janan Eppig.

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Mouse Genome Informatics (MGI) - Video

Forester XT EJ255 + TurboXS 3" StealthBack Catted + STI Genome Axelback
SSR Disculpenme el desenfoque, pero mi mina estaba grabando... Y disculpen lo sucio del escape... Sorry about the bad focus, but my chick was on cam... and s...

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Forester XT EJ255 + TurboXS 3" StealthBack Catted + STI Genome Axelback - Video

Introduction to Whole Exome and Whole Genome Sequencing
Whole exome and whole genome sequencing are two very new testing techniques that are poised to change the current paradigm of clinical genetic testing. To ge...

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Introduction to Whole Exome and Whole Genome Sequencing - Video

Clinical Applications of Whole Exome and Whole Genome Sequencing
Whole exome and whole genome sequencing are two very new testing techniques that are poised to change the current paradigm of clinical genetic testing. To ge...

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George Church - Keynote: Improving the Accuracy of Genome Sequencing and Interpretation
Our ability to view and alter biology is progressing at an exponential pace -- faster even than electronics. Next generation sequencing can be used to assess...

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Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript. In order to enable it, please see these instructions. 4 hours ago by Marcia Malory Skull of Ursus deningeri. Credit: Wikipedia

(Phys.org) Researchers have reconstructed the mitochondrial genome of a Middle Pleistocene cave bear using a bone sample found in Spain. This is the first time anyone has reconstructed such an old genome from a sample found outside the tundra. To reproduce the genome, Matthias Meyer of the Max Planck Institute for Evolutionary Anthropology in Leipzig and his team devised a new technique for stringing together small DNA strands. In addition to recreating the genome, the team were able to reconstruct the cave bear's phylogeny. The research appears in the Proceedings of the National Academy of Sciences.

DNA fragments over time, largely because of depurination, making it hard to analyze very old samples. The fragmentation rate is temperature-based; DNA from samples recovered from permafrost tends to be less fragmented than DNA from samples found elsewhere. Recently, for example, scientists were able to reconstruct the genome of an approximately 700,000 year old horse from a sample in Canada's Yukon Territory. Until now, however, scientists have only been able to generate sequences from non-permafrost samples about 120,000 years old or younger.

Meyer and his colleagues studied a bone sample from a Middle Pleistocene cave bear (Ursus deningeri). The sample, found at Spain's Sima de los Huesos cave site, was more than 300,000 years old. The researchers believed they could recreate the cave bear's genome by improving the method of DNA extraction.

As DNA samples age, intact sequences become smaller. However, DNA library purification techniques tend to cause the loss of DNA molecules less than 40 bp. To preserve smaller molecules, the team used a single-stranded DNA preparation method used recently in the sequencing of Neanderthal and Denisovan genomes. This method eliminates these purification steps. By combining this single-stranded method with a widely used silica-based DNA extraction technique, the researchers were able to recover and sequence DNA molecules as short as 30 bp.

Meyer's team were able to construct a phylogeny of cave bears, determining that Ursus deningeri diverged from the common ancestor of the Late Pleistocene cave bears Ursus spelaeus and Ursus ingressus at an early stage, to form a sister lineage.

The researchers say it may be possible to sequence DNA molecules even shorter than 30 bp in the future. This will allow geneticists to reconstruct even more Middle Pleistocene genomes, including those from hominin samples at the Sima Los Huesos site, which contains the largest collection of Middle Pleistocene hominin fossils in the world.

Explore further: German researchers publish full Neanderthal genome

More information: Complete mitochondrial genome sequence of a Middle Pleistocene cave bear reconstructed from ultrashort DNA fragments, PNAS, Published online before print September 9, 2013, DOI: 10.1073/pnas.1314445110

Abstract Although an inverse relationship is expected in ancient DNA samples between the number of surviving DNA fragments and their length, ancient DNA sequencing libraries are strikingly deficient in molecules shorter than 40 bp. We find that a loss of short molecules can occur during DNA extraction and present an improved silica-based extraction protocol that enables their efficient retrieval. In combination with single-stranded DNA library preparation, this method enabled us to reconstruct the mitochondrial genome sequence from a Middle Pleistocene cave bear (Ursus deningeri) bone excavated at Sima de los Huesos in the Sierra de Atapuerca, Spain. Phylogenetic reconstructions indicate that the U. deningeri sequence forms an early diverging sister lineage to all Western European Late Pleistocene cave bears. Our results prove that authentic ancient DNA can be preserved for hundreds of thousand years outside of permafrost. Moreover, the techniques presented enable the retrieval of phylogenetically informative sequences from samples in which virtually all DNA is diminished to fragments shorter than 50 bp.

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Researchers reconstruct mitochondrial genome of Middle Pleistocene cave bear

How to Pronounce Genome Wide Association Study
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A fossilized bear bone, from which the genetic material was extracted. / Javier Trueba(MADRID SCIENTIFIC FILMS)

An international team that includes Spanish researchers has sequenced the mitochondrial genome (special DNA passed on exclusively by mothers) of bears who lived about 400,000 years ago in Atapuerca, near Burgos in northern Spain. This brings scientists closer to sequencing the entire genome of pre-Neanderthal humans who lived at the same time, and who hold clues about the evolution of our species.

The small mtDNA fragments were found inside samples of bear bones that were mixed in with hominid fossils at Sima de los Huesos (Pit of the Bones) at the Atapuerca site, which contains the world's largest collection of human remains from the Middle Pleistocene. Until now, the oldest samples of DNA recovered in temperate areas - not frozen at high altitudes - were between 100,000 and 120,000 years old.

The breakthrough could have significant implications for human paleontology.

"Let us hope that the methodology that we are presenting here will help recover ancient DNA sequences from other organisms of the Middle Pleistocene. The fossils of Sima de los Huesos are the target of these efforts," write Jesse Dabney and his colleagues in Proceedings of the National Academy of Sciences (PNAS), which this week publishes the entire mitochondrial genome of those early cave inhabitants.

"Yes, of course I am optimistic about the possibility of obtaining DNA from human fossils at the pit; if it is there in the bear bones, it can be there in the human bones, which are contemporary to the latter," says Juan Luis Arsuaga, co-director of the Atapuerca site and one of the authors of the new study.

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Bear genome at Atapuerca paves way for earliest hominid sequencing at site