8th Translational Research in Mitochondria, Aging, and Disease (TRiMAD) Symposium
In recent years, research focusing on the role of mitochondria as it relates to aging and disease has grown exponentially, bringing great understanding to and growing interest in the mitochondrial mechanisms that impact human disease and aging. The 8th Regional Translational Research in Mitochondria, Aging and Disease TRiMAD Symposium will be host to some of the top investigators in the field.
The Keynote Speaker for this event is Dr. Joann B. Sweasy, Ph.D., Ensign Professor and Vice-Chair, Department of Therapeutic Radiology, Yale University School of Medicine, and Associate Director for Basic Science, Yale Comprehensive Cancer Center. Dr. Sweasy’s research has been continuously funded by the NIH since 1994, and focuses on determining the roles of DNA repair in human diseases, using biochemistry and mouse models. She will speak about her recent research showing the critical roles for DNA repair in preventing the autoimmune disease, systemic lupus erythematosus. The retreat also will include short talks by former graduate students and current Penn State faculty, and a poster session.
Join us on May 19, 2016 in the Berg Auditorium of the Life Sciences Building at the University Park Campus! This event brings together Penn State research communities from the University Park and College of Medicine with a purpose of establishing new collaborations and discussing the existing ones. We are united by our interest in genomics and its applications to medicine. You will learn about the latest research on genomics of metabolic, inflammatory, neurodegenerative, immune, and reproductive system diseases. You will also have a chance to network and meet current and former PSU researchers working in this area.
519 Wartik, videoconferenced to Hershey room #CG623
Jan Hapala, Masaryk University, Czech Republic
Nucleosomes: regulators and protectors
Protein-DNA complexes called nucleosomes are fundamental building blocks of chromatin. They package a long eukaryotic genome into tiny chromosomes. More interestingly, recent years have brought an insight into the role of nucleosomes in the regulation of gene expression. An important regulatory feature of the nucleosome is its positioning. We have used a sequence-based algorithm to study nucleosome positioning around regulatory sites. The results indicate a role of nucleosome positioning in the protection of splice junctions and in the switch mechanism over TATA boxes.
Dennis V. Lavrov, Associate Professor, Chair, Bioinformatics and Computational Biology Graduate Program, Iowa State University
Animal mitochondrial DNA as we don’t know it: mt-genome organization and evolution in non-bilaterian lineages
Animal mitochondrial DNA (mtDNA) is commonly described as a small, circular molecule that is uniform in size, gene content, and organization. However, data collected in the last decade have challenged this view by revealing substantial diversity in animal mitochondrial genomes. Much of this diversity is found in non-bilaterian animals (phyla Cnidaria, Ctenophora, Placozoa, and Porifera), which, from a phylogenetic perspective, form the major branches of the animal tree along with Bilateria. Within these phyla, mtDNA shows variation in size, organization, genetic code, gene content, presence/absence of introns, RNA structures, mRNA processing, and rates of evolution. This newly discovered diversity allows a better understanding of the evolutionary plasticity and conservation of animal mtDNA and can provide insights into the molecular and evolutionary mechanisms shaping mitochondrial genomes.
Presenters will be chosen using the Hat procedure.
Genomics Journal Club - RNA editing
Please join us in discussing the two following articles: (i) Human coding RNA editing is generally nonadaptive, Xu and Zhang, 2014 (ii) In Search of Beneficial Coding RNA Editing, Xu and Zhang, 2015. Let’s focus on the 2014 article, and we will very briefly touch on the 2015 article (just read its abstract). There will be pizzas!
519 Wartik, with video connection to CG628 in Hershey
David Koslicki (Oregon State University)
New Techniques to Analyze the Microbiome: analyze thousands of samples, compare without a reference, and profile a community down to the strain level
I will present a number of techniques (namely: Quikr, EMDeBruijn, and CommonKmers) that I’ve recently developed in collaboration with colleagues, and discuss the advantages and disadvantages of applying these techniques in a variety of circumstances. Quikr is an extremely fast, high level taxonomic profiling tool suitable for understanding the global structure of many metagenomics samples. EMDeBruijn is a reference free, de Bruijn graph-based approach to quantifying the similarities and differences between metagenomic samples, even in the presence of many novel microbial organisms. Finally, CommonKmers is a new, highly accurate taxonomic profiling technique capable of faithfully profiling a community down to the strain level. This technique can then use the resulting taxonomic profile to inform the assembly of a metagenome.
W-257 MSC at University Park; with video to room CG628 at Hershey
Marzia A. Cremona (Politecnico di Milano (Milano, Italy))
Peak shape clustering: an application to GATA-1
In recent years many techniques have been developed to study genetic and epigenetic processes. Among Next Generation Sequencing method, we focus on ChIP-Seq (Chromatin Immuno Precipitation Sequencing), that permits to investigate protein-DNA interactions, e.g. the direct interaction between transcription factors, histones and DNA. At present, in the relevant literature, the analysis of ChIP-Seq data is mainly restricted to the detection of enriched regions (peaks) in the genome, considering only signal intensity. Motivated by the fact that these peaks can show very different shapes, we propose an innovative approach that takes into consideration also the shape of such peaks. We introduce some indices to summarize the shape and we use multivariate clustering techniques in order to detect statistically significant differences in peak shape. We show that an application of this analysis method to ChIP-Seq for the transcription factor GATA-1 reveals novel biological insights. Moreover, we suggest that a functional data analysis approach can lead to even more interesting results, treating peaks directly as curves. Joint work with I. Dellino, A. Parodi, P.G. Pelicci, L. Riva, L.M. Sangalli, P. Secchi and S. Vantini
This year we have joined forces with the Center for Reproductive Biology and Health (CRBH). The combined Physiology/CRBH retreat consists of a one-and-a-half day meeting featuring keynote speakers, faculty and student talks, and poster presentations. This year we are honored to host Drs. Michael Sturek and Carol Bagnell as keynote speakers. The retreat is open to everyone. Attendance is free, but you must register by November 1, 2014. This year we have joined forces with the Center for Reproductive Biology and Health (CRBH). The combined Physiology/CRBH retreat consists of a one-and-a-half day meeting featuring keynote speakers, faculty and student talks, and poster presentations. This year we are honored to host Drs. Michael Sturek and Carol Bagnell as keynote speakers. The retreat is open to everyone. Attendance is free, but you must register by November 1, 2014.
W-257 MSC at University Park; with video to room CG628 at Hershey
Marcelo R. S. Briones (Universidade Federal de Sao Paulo)
Evolution of genetic information in pathogenic microorganisms: Implications for diagnostics and epidemiology
I will briefly present my early work in Trypanosoma cruzi, the causative agent of Chagas disease, and then present my current research in Experimental Microbial Evolution using the pathogenic yeast model, Candida albicans. We study the effects of oxygen concentrations and temperature in morphology and mitochondrial and nuclear genomes. This has major implications for designing typing markers for hospital acquired infections, a severe problem in intensive care units.For more information on Marcelo R. S. Briones. Please visit: http://www.hhmi.org/scientists/marcelo-briones.
The retreat consists of a one-and-a-half day meeting featuring a keynote speaker, faculty and student talks, data visualization workshop and poster presentations. Dr. Peter J. Park as the keynote speaker.
519 Wartik Lab at University Park; with video to room CG623 at Hershey
Dan Mishmar (Ben-Gurion University)
Finally, after 2 billion years, the mitochondrion is part of the general cellular regulation
Billions of years have passed since the fusion event that gave rise to current eukaryotes and their energy producing mitochondria. During that time, the mitochondria, a once free living alpha proteo-bacterium, lost most of its genetic material and became dependent on the cell for its biogenesis. Only 37 genes, which are important for energy metabolism and mitochondrial protein translation, were retained in the current small circular mitochondrial genome. Hence, mitochondrial DNA replication, transcription and post transcriptional regulation are controlled by proteins that are currently encoded by the cell nucleus. It was believed that only a handful of mitochondrial dedicated proteins control mitochondrial function. Hence, one could argue that mitochondria are regulated separately from the rest of the cell. In this talk we will present findings supporting the hypothesis that mitochondria are not only regulated by dedicated factors but are also part of the general cellular regulatory system. We will demonstrate that focusing on mitochondrial DNA transcription and RNA editing. Hence, the long co-existence of the ancient prokaryote within our cells was accompanied by regulatory adaptation.
519 Wartik Lab at University Park; with video to room CG628 at Hershey
Svitlana Tyekucheva (Harvard school of public health)
RNA expression profiling of archival formalin-fixed, paraffin embedded tissues
One challenge limiting development of clinically useful biomarkers for cancer research lies in the paucity of well-annotated frozen specimens with long-term follow-up on which current high-throughput technologies largely rely. Archival formalin fixed paraffin embedded (FFPE) materials represent the only form of clinical specimens in large cohorts with extensive annotation and long-term clinical follow-up. Unfortunately to date no genomic platform has been identified which can accurately interrogate these specimens due to the extensive fixation- and storage-related RNA degradation. First, we compared two commercially available platforms for RNA expression profiling of archival FFPE specimens from clinical studies of prostate and ovarian cancer. The first platform was the Affymetrix microarrays following whole-transcriptome amplification using NuGEN WT-Ovation FFPE System V2. The second platform was the Nanostring nCounter without amplification. For each assay, we profiled 7 prostate cancer and 11 ovarian cancer specimens, with block age range of 4 to 21 years. Both platforms produced gene expression profiles with high sensitivity and reproducibility through technical repeats from FFPE materials of prostate and ovarian cancers. RNA-Seq allows to simultaneously observe gene expression levels, mutations in the coding sequences, splice variants and gene fusions, which are especially important in cancer studies. Therefore, next we determined feasibility of RNA-Seq from archival samples, and identified challenges in the data analysis specific to FFPE by head-to-head comparisons to fresh frozen (FF) specimens using 16 pairs of prostate tumor and adjacent normal samples. We observed high average correlations between gene expression values for FFPE technical replicates, and between FF and FFPE pairs. Conclusions: we assessed two high-throughput approaches ideal for discovery studies (microarray and sequencing) and a more economical approach ideal for simultaneous validation of a developed signature consisting of multiple biomarkers. All platforms generated robust, reproducible data with high-level of intra- and inter-platform concordance, regardless of FFPE block age and RNA integrity. Through this study, we have demonstrated the feasibility of using FFPE materials for biomarker discovery and validation for further integration into clinical practice. For more information on Svitlana Tyekucheva please visit: http://www.hsph.harvard.edu/svitlana-tyekucheva/
University Conference Center, Penn State Hershey campus
The Fourth Annual Retreat of the Center for Medical Genomics (part of the Huck Institutes of the Life Sciences)
The Fourth Annual Retreat of the Center for Medical Genomics (part of the Huck Institutes of the Life Sciences) will be held Tuesday, March 25, 2014 at the Penn State Hershey, University Conference Center. The keynote speaker for this event will be Dr. Beth A. Tarini, M.D., University of Michigan, C.S. Mott Children s Hospital, Department of Pediatrics and Communicable Diseases. Dr. Tarini is Co-Chair of the American Academy of Pediatrics, Genetics in Primary Care Institute. The retreat also will include short talks by Penn State faculty, a poster session, and networking activities. A goal of this retreat is to provide current genomics information and education to the Penn State University research community, particularly researchers wishing to participate in medical research. All sessions are open to all interested participants.
519 Wartik Lab at University Park; with video to room CG628 at Hershey
Prabhani Kuruppumullage Don (Penn State)
Model-based block clustering with EM algorithm
The next meeting of the Center for Medical Genomics will take place at 11 am on Feb 14 (Fri). Our speaker will be Prabhani Kuruppumullage Don and she will talk about “Model-based block clustering with EM algorithm”. Prabhani is a statistician, and she has been working on the development of novel and powerful methods for analysis of genomic and medical data. For instance, Prabhani has been working with Francesca Chiaromonte and me on segmenting the human genome into regions differing in mutation rates and patterns, and this work has implications for evaluating disease-causing variants. Prabhani has recently given this talk at Harvard, and it was very well received.
Privacy preserving data sharing for genome-wide association studies
The protection of privacy of individual-level information in genome-wide association study (GWAS) databases has been a major concern of researchers following the publication of “an attack” on GWAS data in Homer et al. (2008). Traditional statistical methods for the confidentiality protection do not scale well to deal with GWAS databases and external information on them. The more recent concept of differential privacy provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information. Building on such notions, we propose new methods to release aggregate GWAS data without compromising an individual s privacy. In this talk, we give a brief overview of challenges associated with protecting confidential data, and present methods for releasing differentially private minor allele frequencies, chi-square statistics and p-values. The proposed methods are compared on simulated data and on a GWAS study of canine hair length. Time permitting, we may also discuss preliminary results on the risk-utility analysis on a dataset consisting of DNA samples collected by the Wellcome Trust Case Control Consortium (WTCCC), and a privacy-preserving method for finding genome-wide associations based on a differentially private approach to penalized logistic regression.
The purpose of this workshop is to identify research needs and advance collaborative research efforts on computational and statistical analyses of genomic data.
Topics: Computational challenges for comprehensive detection of genome variation; Selection on non-genic regions of the genome: Would we know it if we saw it?; Statistical approaches for integrating data on variation across the genomic landscape; Evolution of the genomic landscape;This workshop is sponsored by the Center for System Genomics & Center for Medical Genomics. For more information on Computational and Statistical Genomics Workshop please visit: http://csg.psu.edu/workshops/system-genomics-workshop