Please see the following email.

--
Ashish Kumar
Bioinformatics and Statistical analysis
Cardio Medicine, University of Oxford
Wellcome Trust Centre for Human Genetics
Roosevelt Drive, OXFORD
OX3 7BN

Tel: +44 (0) 1865 287715
Fax: +44 (0) 1865 287586


-----Original Message-----
From: Jennifer Taylor
Sent: 02 April 2008 11:37
Subject: [Everyone] Bioinformatics Symposium : Analysis of Alternate
Splicing

Dear All,

A Bioinformatics Symposium will be hosted in the Oxford Centre for Gene
Function on the 24th of April 1 p.m. - 5 p.m.

The topic will be methods for the observation and analysis of alternate
splicing, particularly in genome-wide and high-throughput contexts. A full
programme is attached. If you have any queries regarding the programme
please contact Jennifer Taylor ([log in to unmask]) or Jotun Hein
([log in to unmask]).

Everyone is welcome, however numbers are limited so attendees are invited to
register via email with Madeline Mitchell ([log in to unmask]).

Best wishes
Jen Taylor

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Bioinformatics Day on " Alternative Splicing"

April 24’th 2008 - 1pm - 5pm in the Oxford Centre for Gene Function, Oxford

On April 28’th a Bioinformatics Day with focus on alternate splicing will
take place. If you wish to attend this event, please send an email to
Madeline Mitchell ([log in to unmask]) with your name and affiliation.
There is a limit of 100 people in the seminar room in the OCGF, if early
indications are that this is exceeded other venues can be found.
Refreshments will be provided and are generously sponsored by Affymetrix.

1.00 Jotun Hein: Short Welcome

1.10 Jennifer Taylor (Wellcome Trust Centre for Human Genetics - WTCHG):
High-throughput observation of alternate splicing : Progress to date
The observation of transcript diversity arising through alternate splicing
on genome-wide is now a reality, made possible by emerging high-throughput
approaches such as the Affymetrix Human Exon array, high-resolution tiling
arrays and resequencing approaches. As expression profiling datasets emerge
using these platforms,there is a substantial research effort underway to
develop relevant analytical approaches that robustly normalize and summarise
the data and infer transcript splice forms. This introduction will discuss
the major high-throughput platforms sensitive to alternate splicing and the
challenges and approaches identified to date with respect to mining these
rich datasets.

1.35 Deborah Keenan (Affymetrix UK Ltd): Genome-wide Alternative Splicing
Analysis on a Single Array – The Affymetrix GeneChip® Exon 1.0 ST Array 
Alternative splicing is a major source of protein diversity for higher
eukaryotic organisms and is frequently regulated in a developmental
stage-specific or tissuespecific manner. Current estimates suggest that
50-75% (or more) of human genes have multiple isoforms. Exon-level
expression profiling can now be conducted on a single microarray. The
Affymetrix GeneChip® Exon Arrays, combined with the whole transcript
amplification assay (WTA), enable researchers to understand at a global
level how alternative splicing impacts crucial regulatory mechanisms in
development, differentiation and disease pathogenesis. GeneChip Exon® arrays
represent almost all protein-coding transcripts in the genome, including
both empirically supported and predicted transcribed sequences for novel
isoform discovery. Affymetrix Expression Console™ Software provides a
platform for primary exon-level data analysis data quality control and
normalisation. The NetAffx™ Analysis Centre provides array design
information, probe sequence and functional annotation for faster translation
of array data to biological stories. Further statistical evaluation and
biological interpretation can be achieved through a number of GeneChip®
compatible third-party software providers. Affymetrix continues to support
academic and third-party software developers to further evolve ways for
exploring Exon array data.

2.00 George Nicholson (Dept Statistics): A robust statistical method for the
detection of alternatively spliced mRNAs from Affymetrix exon arrays It is
estimated that as many as 75% of genes in the human genome engage in
production of multiple alternative splice variants (mRNA isoforms) from the
same base sequence. Knowledge of which isoforms are created on specific
physiological, genetic and environmental backgrounds will expedite the
discovery of novel associations - as well as the characterisation of known
ones - between genetic polymorphism and disease, and is also an important
step in the integration of transcriptomics and proteomics.
The development of microarray technology over the past decade has permitted
the study of mRNA transcript abundance on a genome-wide scale. It is now
feasible to assess simultaneously the level of expression at all known exons
in the human genome, using the Affymetrix Exon 1.0 ST Array platform.
Statistical methodology for extracting informative signal from such a wealth
of data is required. Here we describe a statistical method for the robust
discovery of novel splice variants; the method is designed to attain a low
rate of false discoveries.

2.25 Claire Vandiedonck (WTCHG): Mapping haplotype-specific gene expression
and alternative splicing in the human Major Histocompatibility Complex
The human Major Histocompatibility Complex (MHC) has been a paradigm for
genomics and disease association mapping. This is the most gene dense and
polymorphic region in the genome with nearly half of known genes involved in
the immune response. The region is associated with many diseases, notably
autoimmune disorders, and recently the MHC was entirely re-sequenced for
frequent haplotypes associated with common autoimmune diseases. Little is
known about splicing in the MHC, but alternative splicing is predicted to
play a major role in the immune system. Here, using an original hybrid
array, including both a tiling path
for the discovery of new transcripts and splicing probes to monitor every
known or predicted splicing events, we draw the first transcriptional map of
the MHC in the context of immune related haplotypes in lymphoblastoid cell
lines. This study is the initial step of our attempt to map MHC expression
and splicing QTLs which should facilitate fine mapping and functional
analysis of genetic polymorphisms for future population-based association
studies.

2.50 -3.30 BREAK

3.30 Rune Lyngsø (Dept. Statistics): How many transcripts does it take to
reconstruct the splice graph?
Alternative splicing has emerged as an important biological process which
increases the number of transcripts obtainable from a gene. Given a sample
of transcripts, the alternative splicing graph (ASG) can be constructed-a
mathematical object minimally explaining these transcripts. Most research
has so far been devoted to the reconstruction of ASGs from a sample of
transcripts, but little has been done on the confidence we can have in these
ASGs providing the full picture of alternative splicing. There is evidence
of a stochastic element to splicing events, so we introduce probabilistic
models of transcript generation, under which growth of the inferred ASG is
investigated. These models are used in novel methods to determine the nature
of the collection of real transcripts from which the ASG was derived. 

3.55 Gromak (Dunn School of Pathology): Co-transcriptional cleavage of
intronic RNAs as a mechanism of eukaryotic gene regulation 
Most human genes contain relatively short exons separated by long tracts of
non-coding intronic sequences. Transcription of these long introns can
result in the accumulation of vast amounts of pre-mRNA near the site of
transcription which might interfere with the ability of the splicing
machinery to find the correct splice sites. Therefore, removal of long
introns from the nascent pre-mRNA transcript is likely to be a critical
process requiring careful regulation. Our previous studies have demonstrated
that exons of the nascent pre-mRNA are tethered to the elongating RNA
polymerase II transcription complex, and that the continuity of the nascent
intronic sequences is not essential for efficient constitutive splicing.
Here we show that intronic cleavage can modulate alternative splicing if it
is positioned between the exon and its intronic regulatory sequences. We
speculate that many human introns contain naturally occurring target
sequences for endonucleolytic cotranscriptional cleavage activity.

4.20 Eleanor Whitfield (EMBL-EBI, UK): The Alternative Splicing and
Transcript Diversity Database
The Alternative Splicing and Transcript Diversity (ASTD) database is a new
database available at the European Bioinformatics Institute. This database
is a result of the merging, continuation and improvement of the Alternative
Splicing Database (ASD) and the Alternative Transcript Diversity database
(ATD), previously maintained at the EBI.
The ASTD database has genome wide alternative splicing data for human, mouse
and rat. The aim of the database is to predict full-length transcripts for
all three species using all publically available EST and mRNA data. Pairwise
comparison of transcripts for each gene, allows us to display alternative
splice events within the transcriptome. Transcripts are annotated for
alternative transcription start sites, alternative polyadenylation sites,
splice events, SNPs and splice site conservation information between
orthologous species. eVOC annotations for each transcript also allows us to
display potential expression patterns. Translations are derived for each
transcript where possible, and, if relevant, are tagged as potential
candidates for nonsense-mediated RNA decay.



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