426 research outputs found
Topological network alignment uncovers biological function and phylogeny
Sequence comparison and alignment has had an enormous impact on our
understanding of evolution, biology, and disease. Comparison and alignment of
biological networks will likely have a similar impact. Existing network
alignments use information external to the networks, such as sequence, because
no good algorithm for purely topological alignment has yet been devised. In
this paper, we present a novel algorithm based solely on network topology, that
can be used to align any two networks. We apply it to biological networks to
produce by far the most complete topological alignments of biological networks
to date. We demonstrate that both species phylogeny and detailed biological
function of individual proteins can be extracted from our alignments.
Topology-based alignments have the potential to provide a completely new,
independent source of phylogenetic information. Our alignment of the
protein-protein interaction networks of two very different species--yeast and
human--indicate that even distant species share a surprising amount of network
topology with each other, suggesting broad similarities in internal cellular
wiring across all life on Earth.Comment: Algorithm explained in more details. Additional analysis adde
Global Network Alignment
Motivation: High-throughput methods for detecting molecular interactions have lead to a plethora of biological network data with much more yet to come, stimulating the development of techniques for biological network alignment. Analogous to sequence alignment, efficient and reliable network alignment methods will improve our understanding of biological systems. Network alignment is computationally hard. Hence, devising efficient network alignment heuristics is currently one of the foremost challenges in computational biology. 

Results: We present a superior heuristic network alignment algorithm, called Matching-based GRAph ALigner (M-GRAAL), which can process and integrate any number and type of similarity measures between network nodes (e.g., proteins), including, but not limited to, any topological network similarity measure, sequence similarity, functional similarity, and structural similarity. This is efficient in resolving ties in similarity measures and in finding a combination of similarity measures yielding the largest biologically sound alignments. When used to align protein-protein interaction (PPI) networks of various species, M-GRAAL exposes the largest known functional and contiguous regions of network similarity. Hence, we use M-GRAAL’s alignments to predict functions of un-annotated proteins in yeast, human, and bacteria _C. jejuni_ and _E. coli_. Furthermore, using M-GRAAL to compare PPI networks of different herpes viruses, we reconstruct their phylogenetic relationship and our phylogenetic tree is the same as sequenced-based one
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
SANA NetGO: A combinatorial approach to using Gene Ontology (GO) terms to score network alignments
Gene Ontology (GO) terms are frequently used to score alignments between
protein-protein interaction (PPI) networks. Methods exist to measure the GO
similarity between two proteins in isolation, but pairs of proteins in a
network alignment are not isolated: each pairing is implicitly dependent upon
every other pairing via the alignment itself. Current methods fail to take into
account the frequency of GO terms across the networks, and attempt to account
for common GO terms in an ad hoc fashion by imposing arbitrary rules on when to
"allow" GO terms based on their location in the GO hierarchy, rather than using
readily available frequency information in the PPI networks themselves. Here we
develop a new measure, NetGO, that naturally weighs infrequent, informative GO
terms more heavily than frequent, less informative GO terms, without requiring
arbitrary cutoffs. In particular, NetGO down-weights the score of frequent GO
terms according to their frequency in the networks being aligned. This is a
global measure applicable only to alignments, independent of pairwise GO
measures, in the same sense that the edge-based EC or S3 scores are global
measures of topological similarity independent of pairwise topological
similarities. We demonstrate the superiority of NetGO by creating alignments of
predetermined quality based on homologous pairs of nodes and show that NetGO
correlates with alignment quality much better than any existing GO-based
alignment measures. We also demonstrate that NetGO provides a measure of
taxonomic similarity between species, consistent with existing taxonomic
measures--a feature not shared with existing GO-based network alignment
measures. Finally, we re-score alignments produced by almost a dozen aligners
from a previous study and show that NetGO does a better job than existing
measures at separating good alignments from bad ones
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