5,621 research outputs found
Protein multi-scale organization through graph partitioning and robustness analysis: Application to the myosin-myosin light chain interaction
Despite the recognized importance of the multi-scale spatio-temporal
organization of proteins, most computational tools can only access a limited
spectrum of time and spatial scales, thereby ignoring the effects on protein
behavior of the intricate coupling between the different scales. Starting from
a physico-chemical atomistic network of interactions that encodes the structure
of the protein, we introduce a methodology based on multi-scale graph
partitioning that can uncover partitions and levels of organization of proteins
that span the whole range of scales, revealing biological features occurring at
different levels of organization and tracking their effect across scales.
Additionally, we introduce a measure of robustness to quantify the relevance of
the partitions through the generation of biochemically-motivated surrogate
random graph models. We apply the method to four distinct conformations of
myosin tail interacting protein, a protein from the molecular motor of the
malaria parasite, and study properties that have been experimentally addressed
such as the closing mechanism, the presence of conserved clusters, and the
identification through computational mutational analysis of key residues for
binding.Comment: 13 pages, 7 Postscript figure
Efficient seeding techniques for protein similarity search
We apply the concept of subset seeds proposed in [1] to similarity search in
protein sequences. The main question studied is the design of efficient seed
alphabets to construct seeds with optimal sensitivity/selectivity trade-offs.
We propose several different design methods and use them to construct several
alphabets.We then perform an analysis of seeds built over those alphabet and
compare them with the standard Blastp seeding method [2,3], as well as with the
family of vector seeds proposed in [4]. While the formalism of subset seed is
less expressive (but less costly to implement) than the accumulative principle
used in Blastp and vector seeds, our seeds show a similar or even better
performance than Blastp on Bernoulli models of proteins compatible with the
common BLOSUM62 matrix
Latent tree models
Latent tree models are graphical models defined on trees, in which only a
subset of variables is observed. They were first discussed by Judea Pearl as
tree-decomposable distributions to generalise star-decomposable distributions
such as the latent class model. Latent tree models, or their submodels, are
widely used in: phylogenetic analysis, network tomography, computer vision,
causal modeling, and data clustering. They also contain other well-known
classes of models like hidden Markov models, Brownian motion tree model, the
Ising model on a tree, and many popular models used in phylogenetics. This
article offers a concise introduction to the theory of latent tree models. We
emphasise the role of tree metrics in the structural description of this model
class, in designing learning algorithms, and in understanding fundamental
limits of what and when can be learned
Efficient seeding techniques for protein similarity search
We apply the concept of subset seeds proposed in [1] to similarity search in
protein sequences. The main question studied is the design of efficient seed
alphabets to construct seeds with optimal sensitivity/selectivity trade-offs.
We propose several different design methods and use them to construct several
alphabets.We then perform an analysis of seeds built over those alphabet and
compare them with the standard Blastp seeding method [2,3], as well as with the
family of vector seeds proposed in [4]. While the formalism of subset seed is
less expressive (but less costly to implement) than the accumulative principle
used in Blastp and vector seeds, our seeds show a similar or even better
performance than Blastp on Bernoulli models of proteins compatible with the
common BLOSUM62 matrix
Automatic identification of highly conserved family regions and relationships in genome wide datasets including remote protein sequences
Identifying shared sequence segments along amino acid sequences generally requires a collection of closely related proteins, most often curated manually from the sequence datasets to suit the purpose at hand. Currently developed statistical methods are strained, however, when the collection contains remote sequences with poor alignment to the rest, or sequences containing multiple domains. In this paper, we propose a completely unsupervised and automated method to identify the shared sequence segments observed in a diverse collection of protein sequences including those present in a smaller fraction of the sequences in the collection, using a combination of sequence alignment, residue conservation scoring and graph-theoretical approaches. Since shared sequence fragments often imply conserved functional or structural attributes, the method produces a table of associations between the sequences and the identified conserved regions that can reveal previously unknown protein families as well as new members to existing ones. We evaluated the biological relevance of the method by clustering the proteins in gold standard datasets and assessing the clustering performance in comparison with previous methods from the literature. We have then applied the proposed method to a genome wide dataset of 17793 human proteins and generated a global association map to each of the 4753 identified conserved regions. Investigations on the major conserved regions revealed that they corresponded strongly to annotated structural domains. This suggests that the method can be useful in predicting novel domains on protein sequences
Probabilistic Clustering of Time-Evolving Distance Data
We present a novel probabilistic clustering model for objects that are
represented via pairwise distances and observed at different time points. The
proposed method utilizes the information given by adjacent time points to find
the underlying cluster structure and obtain a smooth cluster evolution. This
approach allows the number of objects and clusters to differ at every time
point, and no identification on the identities of the objects is needed.
Further, the model does not require the number of clusters being specified in
advance -- they are instead determined automatically using a Dirichlet process
prior. We validate our model on synthetic data showing that the proposed method
is more accurate than state-of-the-art clustering methods. Finally, we use our
dynamic clustering model to analyze and illustrate the evolution of brain
cancer patients over time
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