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Talk Title:
Microbial Genomics, Pangenomics, and Metagenomics in Disease and in Health

Date/Time:
Thursday, February 9th, 2011, 6:00 pm

Affiliation:
Bioinformatician, BCCDC Public Health Microbiology & Reference Laboratory

Abstract:
As DNA sequencing technologies continue to improve, sequencing of microbial genomes can now be done routinely. We have gone from a group of researchers spending years to generated and study one bacterial genome to an individual researcher comparing tens or hundreds of similar genomes at a time with the help of bioinformatic applications. Pangenomic analysis allows us to decipher how a bacterium evolves and how certain small mutations could have a large impact on disease outcome. In recent years, we have also started to sequence the genetic material directly isolated from a microbial community (microbiota) in order to bypass culturing. The International Human Microbiome Consortium and associated efforts are trying to decipher the interactions between our bodies and our microbiotas. The metagenomics approach allows researchers to study an entire microbial community in relation to health and diseases but new challenges arise on how to assign taxonomic and functional information to incomplete and sometimes novel sequences. With the increased scale of sequencing, new bioinformatics and statistical tools are needed to facilitate data process and interpretation. In this talk, I’ll discuss the progress and challenges of microbial genomic analysis with examples drawn from my own research and from literature. Through this talk, I wish to demonstrate that microbial genomics has benefit greatly from the technological improvements over the years and there is a bright future in applying microbial genomics to improve human health.

Please note:
Trainees are invited to meet with the VanBUG speaker for open discussion of both science and career paths. This takes place 4:30-5:30pm in either the Boardroom or Lunchroom on the ground floor of the BCCRC

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Introductory Speaker:
Warren Cheung, PhD candidate, Wasserman lab, CMMT

Title: Biomedical Topic Profiles from Bibliographical Literature Evidence

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Talk Title:
Simulating and Predicting the MicroTargetome

Date/Time:
Thursday, December 8th, 2011, 6:00 pm

Affiliation:
Institut de Recherche en Immunologie et en Cancérologie and Département d’Informatique et de Recherche Opérationnelle, Université de Montréal

URL:
http://www.iro.umontreal.ca/~major/

Abstract:
Protein output determines cell types and states. In animals, microRNAs (miRNAs) are key actors in controlling protein output. Mature miRNAs are about 22-nucleotide long. They are loaded in RNA-induced silencing complexes (RISCs), which bind to miRNA complementary sites in messenger RNAs (mRNAs) to repress their translation. Besides, recent studies indicate that various non-coding RNAs control protein output by competitive attraction of miRNAs. I will present an algorithm to predict the microTargetome, i.e. the RISC/mRNA matching, which considers all competing endogenous RNAs (ceRNAs). The model uses a free-energy of hybridization, and an algorithm that mimics miRNA competition and cooperation. Using this algorithm, we simulated the overexpression of single miRNAs in a specific cell line, and derived a series of biological consequences related to such a protein expression control system. MiRNA, ceRNA, and mRNA levels vary in different cell types and states, including cancer cells. Understanding and predicting microTargetome changes could thus bring insights into the role of RNA in cell differentiation, as well as in cancer development and progression.

Please note:
Trainees are invited to meet with the VanBUG speaker for open discussion of both science and career paths. This takes place 4:30-5:30pm in either the Boardroom or Lunchroom on the ground floor of the BCCRC

Recommended Readings
MC-Fold and MC-Sym pipeline
Designing artificial RNAs
E2F/mir-20a autoregulatory feedback loop

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Introductory Speaker:
Fong Chun Chan, MSc candidate, Gascoyne Lab, BC Cancer Research Centre

Title:
Detection of Differentially Expressed Alternative Transcripts using Conventional Microarrays

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Talk Title:
The ruin of gene network analysis by multifunctionality

Date/Time:
Thursday, November 17th, 2011, 6:00 pm

Affiliation:
Associate Professor, Department of Psychiatry, University of British Columbia and Member of the Brain Research Centre

URL:
Paul Pavlidis

Abstract:
A major goal of biology is to identify the functional relationships and interactions among genes and apply this knowledge to make predictive models. In bioinformatics, it is now routine to use various types of gene network and gene function information to interpret
high-throughput experiments. Examples include “GO enrichment”, network-motivated clustering or gene function prediction methods (e.g. “guilt by association”) and candidate gene prioritization methods. I will describe how a phenomenon we call “gene multifunctionality” distorts such analyses. Genes having high multifunctionality are the source of serious biases or artifacts that can distract attention from more interesting signals, cause
misleading results in algorithm evaluations, and generally make meaningfully applying known information on gene function extremely difficult. I will argue that this problem is ignored at our peril, and suggest some possible remedies and strategies for making progress.

Please note:
Trainees are invited to meet with the VanBUG speaker for open discussion
of both science and career paths. This takes place 4:30-5:30pm in either
the Boardroom or Lunchroom on the ground floor of the BCCRC

Recommended Readings
The impact of multifunctional genes on “guilt by association” analysis

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Introductory Speaker:
Rebecca Worsley Hunt, PhD candidate, Wasserman Lab at Centre for Molecular Medicine and Therapeutics (CMMT)

Title:
Genome nucleotide composition and sequence length affect over-representation predictions of transcription factor binding sites in ChIP-based experiments

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Talk Title:
Haploid Assembly of Diploid Genomes

Date/Time:
Thursday, October 13, 2011, 6:00 pm

Affiliation:
Bioinformatics Group Leader, Genome Sciences Centre, BC Cancer Agency and Adjunct Professor, School of Computing Science, Simon Fraser University

URL:
Inanc Birol

Abstract:
Most assembly algorithms in use have an implicit assumption that a sequenced nucleic acid has a haploid-like structure, or at worst that the sequence representing a genomic location is present with a high similarity in the read data. This assumption holds nicely in the case of model organisms, which are usually inbred to reduce haplotypic
diversity, and is even not challenged significantly in the case of human samples because of an evolutionarily recent population bottleneck our species experienced. However, when an organism of interest has a diploid genome with a pronounced distance between haplotypes, or when an environmental sample is investigated that represents a collection of similar species, the assumption fails.

Furthermore, read lengths of popular high throughput sequencing technologies, and even the spatial associations brought by paired end reads are often not enough to completely de-phase the assembled sequences. In this talk, I will discuss the particular challenges one faces during de novo assembly of such datasets, and describe how we
approach to their solution within the ABySS framework.

ABySS is a short read assembly tool, particularly developed to address large scale assembly problems. I will introduce how it handles distance information to extend and scaffold contigs, and how it represents haplotypic information in its output. I will demonstrate its performance on the assembly of the mountain pine beetle genome.

Please note:
Trainees are invited to meet with the VanBUG speaker for open discussion
of both science and career paths. This takes place 4:30-5:30pm in either
the Boardroom or Lunchroom on the ground floor of the BCCRC

Recommended Readings
ABySS
Assemblathon 1

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Introductory Speaker:
Olena Morozova, PhD candidate, Marra Lab, Genome Sciences Centre, BC Cancer Agency

Title:
A wide spectrum of somatic mutation in high-risk neuroblastoma

Presentation:
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Talk Title:
Reconstructing Ancient Genome Architechtures

Date/Time:
Thursday, September 8, 2011, 6:00 pm

Affiliation:
Associate Professor of Mathematics, Simon Fraser University

URL:
Cedric Chauve

Abstract:
Paleogenomics aims at reconstructing the genomes of extinct species, whose DNA can not be sequenced due to molecular decay. Hence the only possible approach is the study of current genomes (i.e. descendants of these extinct species) to detect conserved features that might indicate ancestral genomic characters and then to assemble these characters into ancestral genomes. In this talk I will describe recent (successfull?) efforts to reconstruct the architecture of ancient vertebrate genomes, from placental mammalians to amniotes.

Please note:
Trainees are invited to meet with the VanBUG speaker for open discussion
of both science and career paths. This takes place 5:00-5:45pm in either
the Boardroom or Lunchroom on the ground floor of the BCCRC

Recommended Readings
Reconstructing ancestral genomes
Framework for reconstruction and application to mammalian genomes

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Introductory Speaker:
Christian Frech, PhD candidate, Chen Lab, Simon Fraser University

Title:
Genome comparison of human and non-human malaria parasites reveals species-specific genes potentially linked to human disease

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Make sure that your question gets answered by submitting by email to
dev@vanbug.org.

Panelists:
Benjamin Good, PhD, Postdoctoral Fellow, Genomics Institute of the Novartis Research Foundation
Inanc Birol, PhD, Bioinformatics Group Leader, Michael Smith Genome Sciences Centre, BC Cancer Agency & Adjunct Professor, School of Computing Science, Simon Fraser University
Anthony Fejes, MSc, Co-founder, Zymeworks and PhD candidate, Michael Smith Genome Sciences Centre, BC Cancer Agency
Phil Hieter, PhD, Professor of Medical Genetics, Michael Smith Laboratories, University of British Columbia

Bring your questions to the VanBUG Bioinformatics Careers Panel
Thursday, April 14, 6-7pm. Panelists include a recent Bioinformatics
Training Program graduate currently doing a post-doc at the Genomics
Institute of the Novartis Research Foundation, an entrepreneur who
co-founded Zymeworks, a computational biotech company, a sage academic
who has participated in many UBC hiring committees, and a bioinformatics
group leader from the largest bioinformatics employer in BC.

A 1-hour moderated panel discussion will be followed by networking over
pizza and refreshments.

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Talk Title:
Transcription factor - DNA interactions: cis regulatory codes in the genome

Date/Time:
Thursday, March 17, 2011, 6:00 pm

Affiliation:
Associate Professor of Medicine and Pathology, Harvard Medical School

URL:
Martha Bulyk

Abstract:
The interactions between sequence-specific transcription factors (TFs) and their DNA binding sites are an integral part of the gene regulatory networks within cells. My group developed highly parallel in vitro microarray technology, termed protein binding microarrays (PBMs), for the characterization of the sequence specificities of DNA-protein interactions at high resolution. Using universal PBMs, we have determined the DNA binding specificities of >500 TFs from a wide range of species. These data have permitted us to identify novel TFs and their DNA binding site motifs, predict the target genes and condition-specific regulatory roles of TFs, predict tissue-specific transcriptional enhancers, investigate functional divergence of paralogous TFs within a TF family, investigate the molecular determinants of TF-DNA ‘recognition’ specificity, and distinguish direct versus indirect TF-DNA interactions in vivo. Further analyses of TFs and cis regulatory elements are likely to reveal features of cis regulatory codes important for driving appropriate gene expression patterns.

Please note:
Trainees are invited to meet with the VanBUG speaker for open discussion
of both science and career paths. This takes place 4:30-5:30pm in either
the Boardroom or Lunchroom on the ground floor of the BCCRC

Recommended Readings
Compact, universal DNA microarrays to comprehensively determine transcription-factor binding site specificities.

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Introductory Speaker:
Yvonne Li, PhD Candidate, Jones Lab, Genome Sciences Centre, BCCRC

Title:
A large-scale computational approach to finding new uses for existing drugs

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Talk Title:
Human genomics with large sample size and full genome sequences

Date/Time:
Thursday, March 10, 2011, 6:00 pm

Affiliation:
Professor of Population Genetics, Department of Molecular Biology and Genetics, Cornell University

URL:
Andrew G. Clark

Abstract:
The 1000 Genomes Project has completed its pilot phases including (1) low-coverage whole-genome sequencing of 179 individuals, (2) high-coverage sequencing of two mother–father–child trios; and (3) exon-targeted sequencing of 697 individuals from seven populations. These data present an unprecedented level of detail about the allele frequency spectrum and local haplotype structure of ~15 million SNPs, 1 M indels, and 20,000 structural variants across the human genome. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes. Data from the two trios produced an estimate of 1028 germline mutations per genome per generation. These data also present an opportunity to test for past signatures of natural selection and demographic effects. In a separate study we examined sequence variation in just two genes from the ARIC cohort study of 13,715 people. This analysis resulted in nearly 4x the expected count of singleton variants which were subsequently confirmed. These data are consistent with a very recent explosive population growth model that matches the historical and archeological record. The data are also consistent with the observation that each new full human genome that is sequenced typically finds upwards of 100,000 novel SNPs that are not yet in any database.

Please note:
Trainees are invited to meet with the VanBUG speaker for open discussion
of both science and career paths. This takes place 4:30-5:30pm in either
the Boardroom or Lunchroom on the ground floor of the BCCRC

Recommended Readings:
Human genome variation
Deep resequencing

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Introductory Speaker:
Rodrigo Goya, PhD Candidate, Marra Lab, Genome Science Centre, BCCA & Meyer Lab, Centre for High-Throughput Biology (CHiBi), UBC

Title:
Characterizing alternative expression profiles in cancer samples using RNA-Seq

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Talk Title:
Ancestral genome reconstruction and its uses toward annotating the human genome

Date/Time:
Thursday, January 20, 2011, 6:00 pm

Affiliation:
Assistant Professor, School of Computer Science, McGill University

URL:
Mathieu Blanchette

Abstract:
With the number of sequenced vertebrate genomes rapidly growing, the exciting prospect of being able to accurately infer ancestral genomes becomes within reach. In this presentation, I will discuss how ancestral DNA sequences can be inferred and how they can be then used to help addressing some key questions in genomics. Reconstructing ancestral sequences poses a number of algorithmic challenges. I will first describe some of our work on aligning orthologous sequence and inferring ancestral sequences, focusing on the accurate identification of insertions and deletions. Next, I will discuss how one can take advantage of the availability of inferred ancestral sequences to help at three important tasks: (i) identify non-coding sites under selection in the human genome; (ii) improve the detection of transcription factor binding sites; and (iii) determine the target gene(s) of long-range enhancers. Evolution has been conducting site-specific functionality assays for hundreds of millions of years. The ability to decipher the results of these experiments has and will continue to provide us with a wealth of information about our genome and the impact of mutations.

Please note:
Trainees are invited to meet with the VanBUG speaker for open discussion
of both science and career paths. This takes place 4:30-5:30pm in either
the Boardroom or Lunchroom on the ground floor of the BCCRC

Recommended Readings
Reconstructing large regions of an ancestral mammalian genome in silico

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Introductory Speaker:
Thomas Hentrich, PhD Candidate, Gupta Lab, University of British Columbia

Title:
Modelling a biomolecular flip-flop based on RNA interference

Presentation:
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Talk Title:
Constrained Principal Component Analysis for fMRI Data: Relating fMRI Signal to Experimental Conditions.

Date/Time:
Thursday, December 9, 2010, 6:00 pm

Affiliation:
Assistant Professor, Department of Psychiatry, University of British Columbia

URL:
Todd Woodward

Abstract:
Functional magnetic resonance imaging (fMRI) data from one subject
typically involves measurement of blood-oxygen level dependent (BOLD)
changes in the whole brain, measured every two seconds, over a period
of about 12 minutes, at 65,000 brain regions. Over this 12 minute
period, participants are asked to repeatedly carry out some cognitive
task, for example, to remember 8 numbers for a short period of time
(e.g., 4 seconds). Researchers using this technology need to determine
which brain networks are invoked in response to the task (and not some
other aspect of thinking, like “this scanner is uncomfortable!”), but
also (and importantly), which are differentially involved in the
experimental conditions that are built into the task. The method that
our laboratory has developed for this purpose is named constrained
principal component analysis (fMRI-CPCA), and combines multivariate
multiple regression with principal component analysis (i.e., singular
value decomposition). Multivariate multiple regression is used to
separate the BOLD signal variance into what is predictable from the
task and what is not, and singular value decomposition is used to
determine the dominant patterns of intercorrelation between the brain
regions for each source of BOLD signal variance, thereby forming brain
networks. Changes over time in these brain networks can be correlated
with the timing of the task to determine their relative involvement in
the experimental conditions. fMRI-CPCA is available for download free
of charge ( http://www.nitrc.org/projects/fmricpca).

Please note:
Trainees are invited to meet with the VanBUG speaker for open discussion
of both science and career paths. This takes place 4:30-5:30pm in either
the Boardroom or Lunchroom on the ground floor of the BCCRC

Recommended Readings
FIR-CPCA analysis

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Introductory Speaker:
Raymond Lim, MSc Candidate, Pavlidis Lab, Centre for High Throughput Biology, University of British Columbia

Title:
Wide Scale Comparison of Transcriptome Profiles

Presentation:
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