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Talk Title:
Decoding genetic switches in T helper cell differentiation

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

Affiliation:
Theoretical and Computational Biology, MRC Laboratory of Molecular Biology , Cambridge University, UK

URL:
Sarah Teichmann

Abstract:
Gene expression levels are believed to be continuously distributed from very low to very high levels, with most genes at an intermediate level. We have studied the transcriptome-wide distribution of expression levels in mouse T helper cells using RNA-seq technology, and have developed a variety of ways to model the expected background levels. This is critical for definition of a threshold level of expression of a gene in a given cell type. In order to calibrate the RNA-seq expression levels in terms of molecules of mRNA per cell, we have integrated the RNA-seq data with single molecule mRNA-FISH experiments.
The results of these analyses and experiments show that many genes are expressed at > ~ 1 molecule per cell and that two major expression levels can be identified which vary by roughly one to two orders of magnitude. This gives rise to bimodal distributions of gene expression levels in cell populations. Analysis of histone modifications by ChIP-seq indicates that activating modifications such as H3K9/14ac and H3K4me3 are involved in this ‘digital’ expression switch.
Our findings have broad implications for the analysis RNA-seq and ChIP-seq data and for the understanding of the regulation of gene expression.

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:
Transcription factors
Structural Bioinformatics

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Introductory Speaker:
Anthony Fejes, PhD Candidate, Jones Lab, Genome Sciences Centre, BCCA
Title:
Harnessing Diversity: Leveraging a Database of Human Genome Variations to Tackle Genetic Diseases.

The upcoming 2010-2011 seminars

October 14, 2010 TBA
**Wednesday**November 10, 2010 Dr. Quaid Morris, University of Toronto, Canada
December 9, 2010 TBA
January 13, 2010 TBA
February 10, 2011 TBA
March 10, 2011 Dr. Andy Clark, Cornell University, NY, USA
April 14, 2011 TBA

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Talk Title:
Intrinsically disordered proteins: Regulation and Disease

Date/Time:
Thursday, April 8, 2010, 6:00pm

Affiliation:
Centre for High-Throughput Biology, University of British Columbia

URL:
Joerg Gsponer

Abstract:
Over one-third of all proteins in a eukaryotic cell contain regions that
are intrinsically disordered. Intrinsically disordered proteins (IDPs)
lack a unique 3-dimensional structure, either entirely or in parts, when
alone in solution. Alterations of the endogenous levels of IDPs have
been associated with severe pathological conditions such as
neurodegeneration and cancer. I will discuss strategies that eukaryotic
cells have developed to minimize the potentially harmful effects of IDPs.

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Introductory Speaker:
Kieran O’Neill, PhD Candidate, Ryan Brinkman’s Lab, Bioinformatics Graduate Program, UBC

The upcoming 2009-2010 meeting dates

This is the last VanBUG of the season!
VanBUG seminars will resume in September 2010poster_avr_2010.pdfposter_avr_2010.pdf

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Talk Title:
Using protein design to dissect the form and function of biological networks

Date/Time:
Thursday, March 11, 2010, 6:00pm

Affiliation:
Department of Biology/Computer Science, New York University

URL:
Richard Bonneau

Abstract:

I will discuss recent applications of the Rosetta protein structure prediction and
design platform to understanding genomes. There are two main ways we can use
structural bioinformatics to aid in the building of genome wide models: 1) providing
predictions about the structure, function and interaction of proteins, and 2) designing
new molecules that can be used as tools to specifically perturb individual functions
and interactions. In this talk I will primarily focus on the design of new tools. I will
describe our recent efforts to accurately predict temperature sensitive mutations that
can be used to investigate the effects of essential genes. I will also describe our
efforts to include non-cannonical amino acids and non-canonical backbone structures
(such as N-branched side chains, peptoids) in the design of peptidomimetics that
target specific protein-interactions. All protocols for prediction and design are
seamlessly integrated into the Rosetta package and available at the
Rosetta-commons: http://www.rosettacommons.org/

Presentation:
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Introductory Speaker:
Anamaria Crisan, MSc Candidate, Aparicio Lab, Bioinformatics Graduate Program, UBC

Presentation:
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The upcoming 2009-2010 meeting dates

April 8, 2010 Main Speaker: Joerg Gsponer , Centre for High-Throughput Biology; Intro Speaker: Kieran O’Neill, Brinkman Lab, BCCRC

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Talk Title:
Human Genome Structural Variation, Disease and Evolution

Date/Time:
Wednesday, January 13, 2010, 6:00pm **NOTE DATE CHANGE**

Affiliation:
Department of Genome Sciences, HHMI, University of Washington, Seattle

URL:
Evan Eichler

Abstract:
Structural variation of the genome is an important aspect in our understanding of
human disease and evolution. Accurately characterizing such variation an unmet
challenge of both bioinformatics and genomics. I will focus on the genome-wide
discovery, analysis and distribution of copy-number variants (CNV) and inversion
polymorphisms within human and great ape species. I will present methods to
accurately resolve the copy, content and structure of these regions based on
traditional and next-generation sequence datasets. I will discuss our efforts to
characterize regions of the genome that are prone to recurrent deletion, duplication
and inversion and provide examples of their importance as recurrent and de novo
sources of neuropsychiatric and neurocognitive disease.

Presentation:
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Introductory Speaker:
Parisa Shooshtari

Talk Title:
Faithful Sampling for Spectral Clustering to Analyse High Throughput Flow Cytometry Data

Affiliation:
School of Computing Science, Simon Fraser University
Supervisor: Drs. Arvind Gupta and Ryan Brinkman

Presentation:
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The upcoming 2009-2010 meeting dates

February, 2010 **NO VANBUG DUE TO OLYMPIC WINTER GAMES**

March 11, 2010 Main Speaker: Rich Bonneau , New York University; Intro Speaker: TBD

April 8, 2010 Main Speaker: Joerg Gsponer , Centre for High-Throughput Biology; Intro Speaker: Kieran O’Neill, Brinkman Lab, BCCRC

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Talk Title:
Mutation discovery in cancer using next generation sequencing and probabilistic models

Date/Time:
November 26, 2009, 6:00pm **PLEASE NOTE THE DATE CHANGE**

Molecular Oncology Department, BC Cancer Agency

URL:
Sohrab Shah

Abstract:
The advent of next generation sequencing (NGS) has propelled the field of cancer
genomics forward such that it is now cost-effective to interrogate entire genomes or
transcriptomes of clinical tumor samples for the presence of somatic mutations: often
the key driver genomic alterations in tumorigenesis. Since the number of data points
produced by NGS experiments is in the billions, variant discovery is necessarily a
computational exercise. I will describe the development of novel computational methods
for the discovery of mutations from NGS, based on probabilistic models. I will present
results of applying these approaches in two recent studies in ovarian and breast cancer:
namely the discovery of a novel recurrent and defining mutation in the FOXL2 gene in
granulosa cell tumours of the ovary and the first description of mutational evolution of a
breast cancer seen at nucleotide resolution.

Presentation:
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——————————
Introductory Speaker:
Hye-Jung Elizabeth Chun, MSc Candidate

Talk Title:
Gene expression of breast tumors with different responses to immunotherapy

Affiliation:
Bioinformatics Graduate Program, UBC

Presentation:
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The upcoming 2009-2010 meeting dates

December 10, 2009 Main Speaker: TBD; Intro Speaker: Rodrigo Goya, Marra Lab, Genome Sciences Centre, BCCA

January 13, 2010 **PLEASE NOTE THE DATE CHANGE** Main Speaker: Evan Eichler , University of Washington; Intro Speaker: TBD

March 11, 2010 Main Speaker: Rich Bonneau , New York University; Intro Speaker: TBD

April 8, 2010 Main Speaker: Joerg Gsponer , Centre for High-Throughput Biology; Intro Speaker: Kieran O’Neill, Brinkman Lab, BCCRC

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Talk Title:
Visual Analytics and Biological Information

Date/Time:
October 8, 2009, 6:00pm

Affiliation:
School of Interactive Arts and Technology, SFU

URL:
Chris Shaw

Abstract:
Visual Analytics is the study of analytical reasoning facilitated by interactive visual interfaces. It is an outgrowth of Information Visualization and encompasses expertise from fields such as Statistics, Cognitive Psychology, Social Science, Computer Science, Graphic Design, and Information Design. This talk will give a brief overview of the field of Visual Analytics, and will lead to the introduction of a Visual Analytics system I have developed called IMAS that is aimed at the analysis and visualization of microbial DNA.

Presentation:
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Introductory Speaker:
Francis Ouellette

Talk Title:
The Canadian Bioinformatics Workshops (CBW)

Affiliation:
Ontario Institute for Cancer Research

The upcoming 2009-2010 meeting dates

November 12, 2009
December 10, 2009
January 14, 2010
March 11, 2010
April 8, 2010

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Talk Title:
An Open Source Software Framework for High-Throughput Flow Cytometry Data Analysis and its Application to Discovery and Diagnosis

Date/Time:
September 10, 2009, 6:00pm

Affiliation:
Terry Fox Laboratories, BC Cancer Research Centre

URL:
Ryan Brinkman

Abstract:
High-throughput FCM (HT-FCM) is poised to reshape dramatically biomedical research by increasing the efficiency of an already widely adopted research and clinical tool. However, accelerating data collection requires a similar increase in the ability to analyze data. Successful management of the information generated by HT-FCM techniques requires highly automated methods to extract the relevant information from the large volume of data generated by the measurement of complex treatment-response patterns. This talk will review the development of an integrated computational infrastructure supporting high throughput data quality analysis, normalization, automated gating and sophisticated visualization. Examples will be shown illustrating how we have applied the various tools to support both the discovery of clinical relevant cell populations and aid in patient diagnosis.

Presentation:
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Introductory Speaker:
Andrew McPherson, Bioinformatics Graduate Program

Talk Title:
Methods for gene fusion discovery using RNA-seq

Affiliation:
Centre for Translational and Applied Genomics (CTAG), BC Cancer Research Centre

The upcoming 2009-2010 meeting dates

September 10, 2009
October 8, 2009
November 12, 2009
December 10, 2009
January 14, 2010
March 11, 2010
April 8, 2010

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Talk Title:
Life by the Book: Pragmatically Using Text in Large Scale -Omics

Date/Time:
April 9, 2008, 6:00pm

Affiliation:
School of Computing, Queen’s University

URL:
Hagit Shatkay

Abstract:
The genomic era, which dawned upon us with the sequencing of the human genome, is characterized by tremendous amounts of biomedical data, accompanied by a significant increase in the number of related scientific publications.

Much biomedical knowledge is hidden within the abundant literature. The ability to rapidly and effectively survey the literature can support numerous applications, including multiple stages in the design and the interpretation of large-scale experiments.

A variety of methods are being applied to the biomedical literature in an attempt to meet these goals, mostly through careful mining of text for gene/protein names and interactions, using natural language processing methods. However, the idea
of general “biomedical text mining” remains elusive.

Rather than view biomedical text mining as one monolithic (and not very well
defined) task, we attend to specific biological goals that may benefit from the use of text. The talk will focus on several concrete biological applications/problems involving text, and discuss some non-traditional, coarse-grain methods, that we use to effectively address them.

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Introductory Speaker:

Leon French

Talk Title:
Automated recognition of brain region mentions in biomedical literature

Affiliation:
Pavlidis Lab, UBC Centre for High-througput Biology

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Talk Title:
Digging in data: how computation can be used to drive biological discovery

Date/Time:
March 12, 2009, 6:00pm

Affiliation:
Princeton University, Lewis-Sigler Institute for Integrative Genomics

URL:
Olga Troyanskaya

Abstract:
The explosion of functional genomics data, including microarray,
proteomics, and high-throughput genetic studies, has the promise of a
systems-level view of protein function, interactions, and regulation.
In the future, such systems-level understanding of biology can pave
the way for predictive physiological models and molecular medicine.
However, these data are noisy, computationally diverse, and
biologically heterogeneous. I will discuss our recent work in
developing robust methods for integrated analysis of these data with
the goal of enabling exploration and discovery of novel biology, and
in addressing the disconnect between computation and experiments
through an integrative computational-experimental framework for
function discovery. We applied these methods to data from human and
model organisms, identifying and experimentally validating previously
unknown protein functions, including several new players in
macroautophagy in human fibroblasts and over 100 new mitochondrial
organization and biogenesis proteins in yeast.

VanBUG is pleased to welcome CSCBC 2009 delegates
For more information on the CSCBC Conference: http://www.cscbc2009.org/

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Introductory Speaker:

Monica Sleumer

Talk Title:
De Novo Detection of Regulatory Elements in C. elegans

Affiliation:
Jones Laboratory, Genome Sciences Centre

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Presentation:
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Talk Title:
Driver and Passenger Mutations in Cancer

Date/Time:
February 12, 2009, 6:00pm

Affiliation:
The Scripps Research Institute

URL:
Nicholas Schork

Abstract:
Recent studies investigating the genetic determinants of cancer suggest that some of the genetic alterations contributing to tumorigenesis may be inherited, but most of them are somatically acquired during the transition of a normal cell to a cancer cell. A systematic understanding of the genetic and molecular determinants of cancers has already begun to have a transformative effect on the study and treatment of cancer, particularly through the identification of a range of genetic alterations in protein kinase genes, which are highly associated with the disease. Since kinases are prominent therapeutic targets for intervention within the cancer cell, studying the impact that genomic alterations within them have on cancer initiation, progression, and treatment is both logical and timely. In fact, recent sequencing and resequencing (i.e., polymorphism identification) efforts have catalyzed the quest for protein kinase ‘driver’ mutations (i.e., those genetic alterations which contribute to the transformation of a normal cell to a proliferating cancerous cell) in distinction to kinase ‘passenger’ mutations which reflect mutations that merely build up in course of normal and unchecked (i.e., cancerous) somatic cell replication and proliferation. In this review, we discuss the recent progress in the discovery and functional characterization of protein kinase cancer driver mutations and the implications of this progress for understanding tumorigenesis as well as the design of ‘personalized’ cancer therapeutics that target an individual’s unique mutational profile.

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Introductory Speaker:

Ismael Vergara

Presentation:
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Talk Title:
Polymorphic segmental duplications in the nematode Caenorhabditis elegans

Affiliation:
Jack Chen Laboratory, SFU