Search arXivSearch

arXiv · 1805.09884

Ridge Regression Estimated Linear Probability Model Predictions of O-glycosylation in Proteins with Structural and Sequence Data

Abstract

The likelihood of O-GlcNAc glycosylation in human proteins is predicted using the ridge regression estimated linear probability model (LPM). To achieve this, sequences from three similar post-translational modifications (PTMs) of proteins occurring at, or very near, the S or T site are analyzed: N-glycosylation, O-mucin type (O-GalNAc) glycosylation, and phosphorylation. Results found include: 1) The consensus composite sequon for O-glycosylation does NOT have W on either side of the glycosylation site. 2) The same holds for the consensus sequon for phosphorylation. 3) For LPM estimation, N-glycosylated sequences are found to be good approximations to non-O-glycosylatable sequences. 4) The selective positioning of an amino acid along the sequence, differentiates the PTMs of proteins. 5) Some N-glycosylated sequences are also phosphorylated at the S or T site. 6) ASA values for N-glycosylated sequences are stochastically larger than those for O-GlcNAc glycosylated sequences. 7) Structural attributes (beta turn II, II', helix, beta bridges, beta hairpin, and the phi angle) are significant LPM predictors of O-GlcNAc glycosylation. The LPM with sequence and structural data as explanatory variables yields a Kolmogorov-Smirnov (KS) statistic value of 99%. 8) With only sequence data, the KS statistic erodes to 80%, underscoring the germaneness of structural information, which is sparse on O-glycosylated sequences. With 50% as the cutoff probability for predicting O-GlcNAc glycosylation, this LPM mispredicts 21% of out-of-sample O-GlcNAc glycosylated sequences as not being glycosylated. The 95% confidence interval around this mispredictions rate is 16% to 26%

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Rajaram Gana, Sona Vasudevan. 2019-02-16. Ridge Regression Estimated Linear Probability Model Predictions of O-glycosylation in Proteins with Structural and Sequence Data. https://doi.org/10.1186/s12860-019-0200-9

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

Lightning-fast adaptive immune receptor similarity search by symmetric deletion lookup

An individual's adaptive immune receptor (AIR) repertoire records immune history due to the receptors' antigen specificity. Reading this record requires computational approaches for inferring receptor function from sequence, as the diversity of possible receptor-antigen pairs vastly outstrips experimental knowledge. Identification of AIRs with similar sequence and thus putatively similar function is a common performance bottleneck in these approaches. Here, we benchmark the runtime scaling of five algorithmic approaches to radius-based search for Levenshtein neighbors. We show that a symmetric deletion lookup approach, originally proposed for spell-checking, is particularly scalable. We introduce SymScan and XTNeighbor, optimized CPU and GPU software implementing a parallelized variant of the algorithm. For one million input sequences, these tools identify all sequence pairs that differ by one or two edits in seconds, orders of magnitude faster than existing approaches. We demonstrate how symmetric deletion lookup can be integrated as a pre-filtering step in T cell receptor metaclone discovery and B cell receptor lineage identification. Our contribution is poised to greatly accelerate existing analysis pipelines and enable processing of immunosequencing data at scale.

q-bio.QM

Implication of modelling choices on connectivity estimation: A comparative analysis

Landscape connectivity is an important field with important conservation implications. Connectivity modelling is a useful tool to inform and guide landscape planning. However, it involves assumptions and methodological decisions which ultimately impact connectivity outcomes. In order to understand the implications of modelling choices on final connectivity estimations, we compare two landscape characterisation approaches - expert knowledge and species distribution models - and three movements models - least-cost paths, circuit theory and an individual-based movement simulator. The implementation of the models and the construction of the analyses scope highlighted conceptual and methodological differences that made the comparison difficult. Landscape characterisation appears as the principal factor determining connectivity outcomes. Therefore, the confrontation between expert knowledge and species distribution models is critical to leverage points of convergence and complementarity between these two approaches. Conceptual differences between movement models are reported on connectivity map and habitat patch contribution estimations. In the want of data and protocol design specifically to validate connectivity models, approaches that integrate stochastic and behavioural processes, bring a more realistic perspective to connectivity estimation.

q-bio.QM

Triplication: an important component of the modern scientific method

A scientific-study protocol (defined) is designed to deliver results from which inductive inference is allowed. In the nineteenth century, triplication was introduced into the plant sciences and Fisher's p<0.05 rule (1925) incorporated into triple-result protocols designed to counter random/systematic errors which contribute to real-world variability. The aims of the present study were to: (1) classify replication protocols; (2) assess their prevalence in plant-science studies (published during one twenty-first-century year; for defined variable construct); (3) explore triplication rationale. Methods: a plant-sciences protocol-prevalence report was produced; experimental/associational-study proportions analyzed; and real-world-data proxies used to show confidence-interval-width patterns with increasing replicate number. Results: 25% plant-science studies analyzed showed triplication, including 11% triple-result protocols (including greater replicate numbers: 48%;17%, respectively). Theoretical considerations indicated that even if systematic errors predominate, (previously-known) square-root rules sometimes apply, contributing to triplication importance (exemplified by real-world-data proxies). Conclusions: The defined protocols, with minor modifications, should provide the means for assessment of most sciences. Triplication was extensively applied in studies analysed and there are strong methodological reasons why triplication, rather than duplication/quadruplication, is the appropriate standard: triple-result protocols: (a) effectively reduce false positives to acceptable levels; (b) give qualitatively-different information (shape) from duplication; (c) have a large efficiency advantage (concerning confidence-interval widths) over quadruplication. The application of batch replication is not, primarily, a statistical problem and cannot effectively be replaced by simulation.

q-bio.QM