179,744 research outputs found
An HMM-based Comparative Genomic Framework for Detecting Introgression in Eukaryotes
One outcome of interspecific hybridization and subsequent effects of
evolutionary forces is introgression, which is the integration of genetic
material from one species into the genome of an individual in another species.
The evolution of several groups of eukaryotic species has involved
hybridization, and cases of adaptation through introgression have been already
established. In this work, we report on a new comparative genomic framework for
detecting introgression in genomes, called PhyloNet-HMM, which combines
phylogenetic networks, that capture reticulate evolutionary relationships among
genomes, with hidden Markov models (HMMs), that capture dependencies within
genomes. A novel aspect of our work is that it also accounts for incomplete
lineage sorting and dependence across loci.
Application of our model to variation data from chromosome 7 in the mouse
(Mus musculus domesticus) genome detects a recently reported adaptive
introgression event involving the rodent poison resistance gene Vkorc1, in
addition to other newly detected introgression regions. Based on our analysis,
it is estimated that about 12% of all sites withinchromosome 7 are of
introgressive origin (these cover about 18 Mbp of chromosome 7, and over 300
genes). Further, our model detects no introgression in two negative control
data sets. Our work provides a powerful framework for systematic analysis of
introgression while simultaneously accounting for dependence across sites,
point mutations, recombination, and ancestral polymorphism
Data-driven network alignment
Biological network alignment (NA) aims to find a node mapping between
species' molecular networks that uncovers similar network regions, thus
allowing for transfer of functional knowledge between the aligned nodes.
However, current NA methods do not end up aligning functionally related nodes.
A likely reason is that they assume it is topologically similar nodes that are
functionally related. However, we show that this assumption does not hold well.
So, a paradigm shift is needed with how the NA problem is approached. We
redefine NA as a data-driven framework, TARA (daTA-dRiven network Alignment),
which attempts to learn the relationship between topological relatedness and
functional relatedness without assuming that topological relatedness
corresponds to topological similarity, like traditional NA methods do. TARA
trains a classifier to predict whether two nodes from different networks are
functionally related based on their network topological patterns. We find that
TARA is able to make accurate predictions. TARA then takes each pair of nodes
that are predicted as related to be part of an alignment. Like traditional NA
methods, TARA uses this alignment for the across-species transfer of functional
knowledge. Clearly, TARA as currently implemented uses topological but not
protein sequence information for this task. We find that TARA outperforms
existing state-of-the-art NA methods that also use topological information,
WAVE and SANA, and even outperforms or complements a state-of-the-art NA method
that uses both topological and sequence information, PrimAlign. Hence, adding
sequence information to TARA, which is our future work, is likely to further
improve its performance
BioWorkbench: A High-Performance Framework for Managing and Analyzing Bioinformatics Experiments
Advances in sequencing techniques have led to exponential growth in
biological data, demanding the development of large-scale bioinformatics
experiments. Because these experiments are computation- and data-intensive,
they require high-performance computing (HPC) techniques and can benefit from
specialized technologies such as Scientific Workflow Management Systems (SWfMS)
and databases. In this work, we present BioWorkbench, a framework for managing
and analyzing bioinformatics experiments. This framework automatically collects
provenance data, including both performance data from workflow execution and
data from the scientific domain of the workflow application. Provenance data
can be analyzed through a web application that abstracts a set of queries to
the provenance database, simplifying access to provenance information. We
evaluate BioWorkbench using three case studies: SwiftPhylo, a phylogenetic tree
assembly workflow; SwiftGECKO, a comparative genomics workflow; and RASflow, a
RASopathy analysis workflow. We analyze each workflow from both computational
and scientific domain perspectives, by using queries to a provenance and
annotation database. Some of these queries are available as a pre-built feature
of the BioWorkbench web application. Through the provenance data, we show that
the framework is scalable and achieves high-performance, reducing up to 98% of
the case studies execution time. We also show how the application of machine
learning techniques can enrich the analysis process
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