Posts Tagged ‘genomics’

Untangling whole genomes of individual species from a microbial mix

 :: Posted by American Biotechnologist on 05-27-2014

A new approach to studying microbes in the wild will allow scientists to sequence the genomes of individual species from complex mixtures. It marks a big advance for understanding the enormous diversity of microbial communities —including the human microbiome. The work is described in an article published May 22 in Early Online form in the journal G3: Genes|Genomes|Genetics, published by the Genetics Society of America.

“This new method will allow us to discover many currently unknown microbial species that can’t be grown in the lab, while simultaneously assembling their genome sequences,” says co-author Maitreya Dunham, a biologist at the University of Washington’s Department of Genome Sciences.

Microbial communities, whether sampled from the ocean floor or a human mouth, are made up of many different species living together. Standard methods for sequencing these communities combine the information from all the different types of microbes in the sample. The result is a hodgepodge of genes that is challenging to analyze, and unknown species in the sample are difficult to discover.

“Our approach tells us which sequence fragments in a mixed sample came from the same genome, allowing us to construct whole genome sequences for individual species in the mix,” says co-author Jay Shendure, also of the University of Washington’s Department of Genome Sciences.

The key advance was to combine standard approaches with a method that maps out which fragments of sequence were once near each other inside a cell. The cells in the sample are first treated with a chemical that links together DNA strands that are in close proximity. Only strands that are inside the same cell will be close enough to link. The DNA is then chopped into bits, and the linked portions are isolated and sequenced.

“This elegant method enables the study of microbes in the environment,” says Brenda Andrews, editor-in-chief of the journal G3: Genes|Genomes|Genetics. Andrews is alsoDirector of the Donnelly Centre and the Charles H. Best Chair of Medical Research at the University of Toronto. “It will open many windows into an otherwise invisible world.”

At a time when personal microbiome sequencing is becoming extremely popular, this method breaks important ground in helping researchers to build a complete picture of the genomic content of complex mixtures of microorganisms. This complete picture will be crucial for understanding the impact of varying microbiome populations and the relevance of particular microorganisms for individual health.

CITATION: Species-Level Deconvolution of Metagenome Assemblies with Hi-C-Based Contact Probability Maps Joshua N. Burton, Ivan Liachko, Maitreya J. Dunham, and Jay Shendure. G3: Genes|Genomes|Genetics g3.114.011825; Early Online May 22, 2014, doi:10.1534/g3.114.011825; PMID 24855317.

Thanks to the Genetics Society of America for contributing this story.

Powerful New Tool for Studying DNA Elements that Regulate Genes

 :: Posted by American Biotechnologist on 03-24-2014

An international team led by researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) has developed a new technique for identifying gene enhancers – sequences of DNA that act to amplify the expression of a specific gene – in the genomes of humans and other mammals. Called SIF-seq, for site-specific integration fluorescence-activated cell sorting followed by sequencing, this new technique complements existing genomic tools, such as ChIP-seq (chromatin immunoprecipitation followed by sequencing), and offers some additional benefits.

“While ChIP-seq is very powerful in that it can query an entire genome for characteristics associated with enhancer activity in a single experiment, it can fail to identify some enhancers and identify some sites as being enhancers when they really aren’t,” says Diane Dickel, a geneticist with Berkeley Lab’s Genomics Division and member of the SIF-seq development team. “SIF-seq is currently capable of testing only hundreds to a few thousand sites for enhancer activity in a single experiment, but can determine enhancer activity more accurately than ChIP-seq and is therefore a very good validation assay for assessing ChIP-seq results.”

Dickel is the lead author of a paper in Nature Methods describing this new technique. The paper is titled “Function-based identification of mammalian enhancers using site-specific integration.”

Read more…

Going Beyond the Central Dogma of Molecular Biology

 :: Posted by American Biotechnologist on 03-18-2014

Our genome, we are taught, operates by sending instructions for the manufacture of proteins from DNA in the nucleus of the cell to the protein-synthesizing machinery in the cytoplasm. These instructions are conveyed by a type of molecule called messenger RNA (mRNA).

Francis Crick , co-discoverer of the structure of the DNA molecule, called the one-way flow of information from DNA to mRNA to protein the “central dogma of molecular biology.”

Yehuda Ben-Shahar and his team at Washington University in St. Louis have discovered that some mRNAs have a side job unrelated to making the protein they encode. They act as regulatory molecules as well, preventing other genes from making protein by marking their mRNA molecules for destruction.

“Our findings show that mRNAS, which are typically thought to act solely as the template for protein translation, can also serve as regulatory RNAs, independent of their protein-coding capacity,” Ben-Shahar said. “They’re not just messengers but also actors in their own right.” The finding was published in the March 18 issue of the new open-access journal eLife.

Although Ben-Shahar’s team, which included neuroscience graduate student Xingguo Zheng and collaborators Aaron DiAntonio and his graduate student Vera Valakh, was studying heat stress in fruit flies when they made this discovery, he suspects this regulatory mechanism is more general than that.

Many other mRNAs, including ones important to human health, will be found to be regulating the levels of proteins other than the ones they encode. Understanding mRNA regulation may provide new purchase on health problems that haven’t yielded to approaches based on Crick’s central dogma.

Read the full story A novel mechanism for fast regulation of gene expression.

Genomics for Judges

 :: Posted by American Biotechnologist on 01-27-2014

Genomic research will eventually uncover a complete picture of how our genetic information, acting in concert with our experiences, influences our behavior, our risk for disease, and our responsiveness to medical treatments. These are all subjects of great academic and personal interest, but what happens when they are connected to a question of legality? When considering whether an individual’s genetic inheritance can be blamed for criminal behavior, or how information on disease predisposition should be used, who is qualified to testify, and what kinds of knowledge are needed to make sound judicial decisions?

The Supreme Court of Illinois and its Administrative Office of the Illinois Courts, in coordination with members of the Illinois Judicial Conference Committee on Education, appointed by the Supreme Court, are responsible for facilitating educational resources for Illinois judges, including those pertaining to sciences in the law. The Institute for Genomic Biology (IGB) at the University of Illinois had the unique opportunity to work with the AOIC in offering a new seminar, “Genomics for(TM) Judges,” that was designed to prepare judges to grapple with legal questions involving DNA sequencing and analysis, as well as related technologies, in the courts today and in the future.

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Free Webinar: ‘Viewing Cancer Genomes at High Resolution’

 :: Posted by American Biotechnologist on 10-08-2013

Large-scale cancer genomics studies have established an extensive and unprecedented catalog of somatic mutations in multiple cancer types. This landscape was determined using mostly highly cellular, untreated primary tumors and is mostly static with limited implications to understand cancer progression and drug response in the clinic.

Tumors are composed of multiple cell types: stromal, immune or malignant cells. Malignant cells can also show sub-clonal heterogeneity, where different clones carry various somatic mutations and show variable oncogenic potential or drug sensitivity. Finally this sub-clonal population can change during the progression of cancer or as a consequence of the treatment. Additional genomic heterogeneity arises through the characteristic signatures of the various mutational processes that drive genome disruption during tumorigenesis, which highly powered technologies are beginning to resolve.

In a webinar presented by Bio-Rad and Genome Biology, Elaine Mardis (Washington University in St Louis), a world leader in the field of cancer genomics, and Olivier Harismendy (University of California San Diego), who is developing clinical assays in which next-generation sequencing is combined with digital PCR, discuss the latest developments and outstanding questions that relate to viewing cancer genomes at high resolution. The webinar will be open for audience discussion.

► Register for the webinar
New York (U.S.A. – New York) Wednesday, October 23, 2013 at 10:00:00 AM EDT
San Francisco (U.S.A. – California) Wednesday, October 23, 2013 at 7:00:00 AM PTD