To view the poster abstracts, click here.
Computational identification of microRNAs and their targets
Dr. Volker Brendel
miRNAs (microRNAs) are small non-coding RNAs that regulate mRNA
degradation
through complementary base pairing with specific target mRNAs. In
recent
years, more than 300 miRNAs have been identified in animals and plants
using a combination of cloning and computational approaches. Using
comparative genomics, it should be possible to identify the complete set
of
miRNAs in a genome. I will review several such studies involving RNA
fold
prediction and sequence property and similarity measures and report on
our
own results predicting miRNA genes in Arabidopsis thaliana and rice.
Pseudogenes and Gene Conversion
Dr. Todd E. Scheetz
Pseudogenes are prevalent throughout the human genome, as well as most
higher
eukaryotes. They are duplications of existing genes that have
accumulated disabling mutations due to lack of evolutionary pressure to
remain
functional.
They are thought to play a role in evolution, providing a source from
which sequence can be "borrowed" to build a new gene or alter an
existing gene's function. However a similar process, gene conversion, is
known to play a role in the development of several diseases.
A previous study performed at the EMBL identified over 19,000
pseudogenes. Our own investigation has identified additional pseudogenes
within the
human genome. Annotation and prioritization of these pseudogenes is
currently underway in our lab, specifically focusing on the issues of
expression and gene conversion.
Metabolic Flux Maps of Central Carbon Metabolism in Plants
Dr. Jacqueline V. Shanks
Metabolic flux quantification is important in the detailed understanding of metabolism. Since fluxes provide a quantitative depiction of carbon flow through competing metabolic pathways, they are an important physiological characteristic akin to levels of transcripts, proteins, and metabolites. However, flux measurements are nontrivial to obtain on a systematic level, especially in plants. We have developed a tool, NMR2Flux, for metabolic flux analysis of soybean embryos and
C. roseus root tissues. This tool combines NMR analysis of biosynthetically derived fractional 13C labeling of proteinogenic amino acids and starch with metabolite balance models. It provides solutions for carbon fluxes through primary metabolic pathways in the cytoplasm, mitochondria and plastids essential for protein, oil, and starch synthesis. The technology is extremely powerful because it considers all of intermediary metabolism - glycolysis, pyruvate metabolism, pentose phosphate pathway, tricarboxylic acid sycle and C1 metabolism.
Phylogenomic analyses of the origins and evolution of meiosis
Dr. John Logsdon
Our ongoing bioinformatic inventory of meiotic genes in eukaryotic genomes indicates that numerous genes-many of which are meiosis-specific-are found among diverse eukaryotic lineages. Our analyses include a variety of protists, including some species thought to be both early-diverging and asexual. Giardia, for example, contains at least five meiosis-specific genes in addition to many other genes
implicated in both meiosis and DNA repair. The evolutionary relationships of these genes have been validated with rigorous phylogenetic analyses. These results
suggest that meiosis evolved early in eukaryotic evolution and that organisms previously thought to be primitively asexual may be capable of meiotic sexual reproduction.
Virus dynamics and evolution during persistent lentivirus infection
Dr. Susan Carpenter
Lentiviruses exist in vivo as a population of related, non-identical genotypes,
commonly referred to as a quasispecies. The quasispecies structure is characteristic of complex adaptive systems and contributes to the high rate of evolution
in lentiviruses that confounds efforts to develop effective vaccines and antiviral therapies. Experimental infection of horses with equine infectious anemia virus (EIAV) provides a unique system for longitudinal studies of lentivirus-host
interactions during stages of clinical disease and clinical quiescence. We will discuss how computational approaches have aided our understanding of EIAV dynamics and evolution in vivo.
Selection of 5' ESTs for full-insert sequencing
Dr. Thomas Bair
We have developed a system for prioritizing the selection of full-lengt
h inserts from 5 prime-end EST sequenced cDNA libraries. The selected c
lones are full-insert sequenced and assembled to high quality standards
-- an expensive process that increases the importance of selecting a m
inimal number of clone candidates, which do not include the true 5' end
of the native transcript. It is also important however, to include as
much diversity in the selection as possible. Our clones, when selected,
are deposited into the Mammalian Gene Collection (MGC) -- a collection
of over 13,000 freely available mouse clones (http:// mgc.nci.nih.gov/
). To date we have submitted 1585 clones to the MGC project, while this
is a small fraction of the total, our submissions comprise the majorit
y of the longer transcripts with transcripts in the 5-7 kb size range c
oming mostly from our group.
Our system has evolved from initially finding clones homologous to know
n and predicted genes and proteins, to consideration of intrinsic chara
cteristics of 5' EST sequences, such as the start codon, quality of a K
ozak consensus sequence, length of the open reading frame etc., to our
latest system that considers these features in addition to the genomic
context. For example, our selections are enhanced by observing other ESTs and gene predictions in the same genomic location, as well as using finished genomic sequence rather than the typically more error filled ESTs. These details are fed into a decision tree machine learning system to pick clones, which then enter our full-insert sequencing pipeline.
We have analyzed the success and utility of the various methods and will present
a summary of effective metrics as well as a comparison of "genomic" clustering vs. a more traditional EST similarity-based approach (UI-cluster) and analyze trends in the two methods of clustering