The Quinlan Lab just published a paper describing the first set of bioinformatics tools to work with nanopore DNA sequencing technologies. Poretools: a toolkit for analyzing nanopore sequence data was published in Bioinformatics online August 20, 2014.
Professor Kimmo Kaski, Dept of Biomedical Engineering & Computational Science - Aalto University, Niina Sandholm, Doctoral of Science (Technology) candidate, Aalto University, and Professor Stephen Rich, University of Virginia
Professor Stephen Rich recently returned from a visit to Aalto University in Helsinki, Finland where he was invited to be the Opponent during the public dissertation defense for doctoral candidate Niina Sandholm. This took place in the customary manner in Finland with the Custos (Chairman) and the Opponent dressed in academic gowns or black tailcoats, carrying their doctoral hats into the hall, while the candidate wears a formal, dark suit to the event. After the Custos opens the proceedings, the doctoral candidate presents the thesis for 20 minutes. This is followed by three to four hours of intensive questioning by the Opponent, and finally the closing formalities. Sandholm’s thesis, Genome-wide associations and computational search for the genetic risk factors for diabetic nephropathy, used a wide range of computational methods to identify risk factors for diabetic nephropathy. Her dissertation work has resulted in the publication of five papers in peer-reviewed journals.
Ryan Layer, PhD, Research Associate in the Quinlan Lab, was selected to give a platform talk at two upcoming conferences this fall. Dr. Layer will discuss new methods for exploring millions of human genomes at the Wellcome Trust Genome Bioinformatics 2014 Conference. This is the premier bioinformatics meeting in the world and will be held September 21-24 in Cambridge, UK. He will also speak at the 64th Annual Meeting of the American Society of Human Genetics. Set to be held October 18-22, 2014 this is the world’s largest human genetics meeting and exposition, with over 6,500 people expected to attend. It provides a forum for presentations and discussion of the latest scientific developments in all areas of human genetics. The program includes 16 invited scientific sessions, 40 platform sessions, as well as thousands of posters on display from submitted abstracts.
In addition, Dr. Layer recently had a paper selected for publication. LUMPY: a probabilistic framework for structural variant discovery was published June 26, 2014 in Genome Biology.
This summer the Center welcomes Aakrosh Ratan, PhD, a new resident faculty member, and Assistant Professor of Public Health Sciences. Dr. Ratan joins the Center from Pennsylvania State University where he worked as a Research Associate with Professor Webb Miller. His primary research interests are comparative genomics, molecular evolution and algorithm design & analysis. Dr. Ratan will be collaborating on projects with CPHG resident and affiliate faculty, including Dr. Tom Loughran and other members of the Cancer Center.
CPHG faculty member, Dr. Aaron Quinlan, gave the plenary session talk at The Biology of Genomes meeting on May 9th. Held annually at Cold Springs Harbor Laboratory in New York, it is considered to be the premier genomics meeting in the world with presentations by many of the top genomic scientists. Dr. Quinlan’s talk described his research which seeks to understand how ovarian cancer genomes evolve subsequent to chemotherapy. He emphasized the importance of this research noting that ovarian cancer has the highest mortality rate among gynecological malignancies, due to the fact that most patients are diagnosed with advanced stage disease, and that the majority develop chemoresistant disease. In order to identify genetic mutations that might give insight into what is driving the acquisition of resistance, the Quinlan Lab sequenced the DNA of patient tumors both before and after chemotherapy. The resulting data yields insight into the common genes and pathways that drive resistance and hint at future personalized therapies.
A study by researchers, including Dr. Aaron Mackey of the Center for Public Health Genomics, was published in a recent edition of BMC Bioinformatics. The study seeks to improve the methods for accurately identifying SNPs and other genomic variants, thus increasing the reliability and usefulness of genomics data in clinical settings. The paper describes BAYSIC (BAYeSian Integrated Caller), a novel algorithm that uses a Bayesian statistical method to combine variant sets produced by different bioinformatic packages into a reliable set of genome variants. Some strengths of BAYSIC highlighted by the authors are that the algorithm integrates data produced from multiple SNP callers, and produces a call set with a posterior probability that is intuitive and can be used for quantitative filtering; BAYSIC is a completely unsupervised method of classification and requires no training on validated data sets; and BAYSIC performance improves along with the sensitivity or specificity gains of the input call sets. BAYSIC: a Bayesian method for combining sets of genome variants with improved specificity and sensitivity can be read in full in the April 12, 2014 issue of BMC Bioinformatics.
A research team, including CPHG members Drs. Larry Mesner, Ani Manichaikul, Stephen Rich and Charles Farber, has used a systems genetics approach in the mouse to identify Bicc1 as a novel regulator of bone mineral density (BMD). BMD is the single strongest predictor of bone fractures, which are experienced by millions of Americans each year. In addition to identifying Bicc1, the team demonstrated that Bicc1 affected BMD by altering the activity of bone-forming osteoblasts. The group also showed, using a novel network-based approach, that Bicc1 influenced osteoblast activity through an interaction with a second gene, Pkd2. Data from two human genome-wide association meta-analyses were used to demonstrate that genetic variation in BICC1 and PKD2 were also associated with BMD in humans.
News of the researchers’ findings was reported in the May 5th issue of UVa Today. The story was also covered by local TV and radio outlets and as a “Research Highlight” in a forthcoming issue of Nature Reviews Endocrinology. The full text of the paper, Bicc1 is a genetic determinant of osteoblastogenesis and bone mineral density, can be found in the online edition of The Journal of Clinical Investigation.
Here are a few highlights from happenings in the Quinlan Lab . . . Ryan Layer started as a postdoc in both the Quinlan and Hall Labs with funding by the Cancer Training Grant. Jim Havrilla began working in the lab as a Biomedical Sciences (BIMS) graduate student. Aaron Quinlan made it to the final 100 competitors for the Moore Foundation’s Data Driven Discovery Award. Ryan Layer presented at the Advances in Genome Biology & Technology (AGBT) Meeting in February after outrunning a snowstorm and driving all night to get there. A new paper has been published in Cell Death and Disease from collaborations with the Concannon Lab (University of Florida): Homozygous mutation of MTPAP causes cellular radiosensitivity and persistent DNA double strand breaks.
Congratulations go out to Dr. E. Kaity Allen on the successful defense of her PhD dissertation! Dr. Allen’s dissertation presentation held April 7th, was entitled “Honing in on genetic risk of chronic otitis media with effusion and/or recurrent otitis media.” The aim of her research was to find novel risk factors that increase OM susceptibility by looking at both host genetics and bacterial communities during upper respiratory tract infection (URTI). This research showed the complex nature of the microbiome of the nasopharynx during URTI and identified novel regions and genes involved in susceptibility to OM. Moreover, functional assays support the participation of previously unsuspected mechanisms in OM pathogenesis. In summary, this research has provided insights into OM susceptibility from both host and bacterial perspectives. Committee members for Allen’s dissertation defense were David Wotton (Chair), Michele Sale (Advisor), Jason Papin (Dean’s Representative), Stefan Bekiranov, Keith Keene, and Ani Manichaikul.
CPHG faculty member, Dr. Aaron Quinlan, is among a select few who have been given early access to the MinION, a portable DNA sequencing device being developed by the U.K. based company Oxford Nanopore Technologies. The device, which is the size of a flash drive and plugs directly into a USB port on a computer, delivers sequence data using nanopore technology. The scientists invited to take part in this program to use the MinION before it is commercially available will have the opportunity to test the device and develop applications in their particular research area. Through this open development process, Oxford Nanopore expects there will be rapid improvement in the performance of the MinION, as well as in the applications for using it.