Using Gaussian model to improve biological sequence comparison.
Ontology highlight
ABSTRACT:
SUBMITTER: Dai Q
PROVIDER: S-EPMC7166749 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:MotivationGaussian network model (GNM) is widely adopted to analyze and understand protein dynamics, function and conformational changes. The existing GNM-based approaches require atomic coordinates of the corresponding protein and cannot be used when only the sequence is known.ResultsWe report, first of its kind, GNM model that allows modeling using the sequence. Our linear regression-based, parameter-free, sequence-derived GNM (L-pfSeqGNM) uses contact maps predicted from the sequence and models local, in the sequence, contact neighborhoods with the linear regression. Empirical benchmarking shows relatively high correlations between the native and the predicted with L-pfSeqGNM B-factors and between the cross-correlations of residue fluctuations derived from the structure- and the sequence-based GNM models. Our results demonstrate that L-pfSeqGNM is an attractive platform to explore protein dynamics. In contrast to the highly used GNMs that require protein structures that number in thousands, our model can be used to study motions for the millions of the readily available sequences, which finds applications in modeling conformational changes, protein-protein interactions and protein functions.
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2017-10-08 | GSE104714 | GEO
Project description:Biological networks provide additional information for the analysis of human diseases, beyond the traditional analysis that focuses on single variables. Gaussian graphical model (GGM), a probability model that characterizes the conditional dependence structure of a set of random variables by a graph, has wide applications in the analysis of biological networks, such as inferring interaction or comparing differential networks. However, existing approaches are either not statistically rigorous or are inefficient for high-dimensional data that include tens of thousands of variables for making inference. In this study, we propose an efficient algorithm to implement the estimation of GGM and obtain p-value and confidence interval for each edge in the graph, based on a recent proposal by Ren et al., 2015. Through simulation studies, we demonstrate that the algorithm is faster by several orders of magnitude than the current implemented algorithm for Ren et al. without losing any accuracy. Then, we apply our algorithm to two real data sets: transcriptomic data from a study of childhood asthma and proteomic data from a study of Alzheimer's disease. We estimate the global gene or protein interaction networks for the disease and healthy samples. The resulting networks reveal interesting interactions and the differential networks between cases and controls show functional relevance to the diseases. In conclusion, we provide a computationally fast algorithm to implement a statistically sound procedure for constructing Gaussian graphical model and making inference with high-dimensional biological data. The algorithm has been implemented in an R package named "FastGGM".
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Project description:With the development of high-throughput sequencing technology, biological sequence data reflecting life information becomes increasingly accessible. Particularly on the background of the COVID-19 pandemic, biological sequence data play an important role in detecting diseases, analyzing the mechanism and discovering specific drugs. In recent years, pretraining models that have emerged in natural language processing have attracted widespread attention in many research fields not only to decrease training cost but also to improve performance on downstream tasks. Pretraining models are used for embedding biological sequence and extracting feature from large biological sequence corpus to comprehensively understand the biological sequence data. In this survey, we provide a broad review on pretraining models for biological sequence data. Moreover, we first introduce biological sequences and corresponding datasets, including brief description and accessible link. Subsequently, we systematically summarize popular pretraining models for biological sequences based on four categories: CNN, word2vec, LSTM and Transformer. Then, we present some applications with proposed pretraining models on downstream tasks to explain the role of pretraining models. Next, we provide a novel pretraining scheme for protein sequences and a multitask benchmark for protein pretraining models. Finally, we discuss the challenges and future directions in pretraining models for biological sequences.
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Project description:An assessment of the equilibrium dynamics of biomolecular systems, and in particular their most cooperative fluctuations accessible under native state conditions, is a first step towards understanding molecular mechanisms relevant to biological function. We present a web-based system, oGNM that enables users to calculate online the shape and dispersion of normal modes of motion for proteins, oligonucleotides and their complexes, or associated biological units, using the Gaussian Network Model (GNM). Computations with the new engine are 5-6 orders of magnitude faster than those using conventional normal mode analyses. Two cases studies illustrate the utility of oGNM. The first shows that the thermal fluctuations predicted for 1250 non-homologous proteins correlate well with X-ray crystallographic data over a broad range [7.3-15 A] of inter-residue interaction cutoff distances and the correlations improve with increasing observation temperatures. The second study, focused on 64 oligonucleotides and oligonucleotide-protein complexes, shows that good agreement with experiments is achieved by representing each nucleotide by three GNM nodes (as opposed to one-node-per-residue in proteins) along with uniform interaction ranges for all components of the complexes. These results open the way to a rapid assessment of the dynamics of DNA/RNA-containing complexes. The server can be accessed at http://ignm.ccbb.pitt.edu/GNM_Online_Calculation.htm.
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