A maximum likelihood method for detecting directional evolution in protein sequences and its application to influenza A virus.
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ABSTRACT:
SUBMITTER: Kosakovsky Pond SL
PROVIDER: S-EPMC2515872 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:MotivationThe task of reconstructing a genomic sequence from a particular species is gaining more and more importance in the light of the rapid development of high-throughput sequencing technologies and their limitations. Applications include not only compensation for missing data in unsequenced genomic regions and the design of oligonucleotide primers for target genes in species with lacking sequence information but also the preparation of customized queries for homology searches.ResultsWe introduce the maxAlike algorithm, which reconstructs a genomic sequence for a specific taxon based on sequence homologs in other species. The input is a multiple sequence alignment and a phylogenetic tree that also contains the target species. For this target species, the algorithm computes nucleotide probabilities at each sequence position. Consensus sequences are then reconstructed based on a certain confidence level. For 37 out of 44 target species in a test dataset, we obtain a significant increase of the reconstruction accuracy compared to both the consensus sequence from the alignment and the sequence of the nearest phylogenetic neighbor. When considering only nucleotides above a confidence limit, maxAlike is significantly better (up to 10%) in all 44 species. The improved sequence reconstruction also leads to an increase of the quality of PCR primer design for yet unsequenced genes: the differences between the expected T(m) and real T(m) of the primer-template duplex can be reduced by ~26% compared with other reconstruction approaches. We also show that the prediction accuracy is robust to common distortions of the input trees. The prediction accuracy drops by only 1% on average across all species for 77% of trees derived from random genomic loci in a test dataset.AvailabilitymaxAlike is available for download and web server at: http://rth.dk/resources/maxAlike.
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Project description:DNA methylation is a reaction that results in the formation of 5-methylcytosine when a methyl group is added to the cytosine’s C5 position. As organisms age, DNA methylation patterns change in a reproducible fashion. This phenomenon has established DNA methylation as a valuable biomarker in aging studies. Epigenetic clocks based on weighted combinations of methylation sites have been developed to accurately predict the age of an individual from their methylome. However, many epigenetic clocks, particularly those that utilize penalized regression, model the changes in methylation linearly with age. Moreover, these models, which use methylation levels as features, are not robust to missing data and do not account for the count-based nature of bisulfite sequence data. Additionally, the models are generally not interpretable. To overcome these challenges, we present BayesAge, an extension of the previously developed scAge approach that was developed for the analysis of single cell DNA methylation datasets. BayesAge utilizes maximum likelihood estimation (MLE) to infer ages, models count data using binomial distributions, and uses LOWESS smoothing to capture the non-linear dynamics between methylation and age. Our approach is designed for use with bulk bisulfite sequencing datasets. BayesAge outperforms scAge in several respects. Specifically, BayesAge’s age residuals are not age associated, thus providing a less biased representation of epigenetic age variation across populations. Moreover, BayesAge enables the estimation of error bounds on age inference and, when run on downsampled data, its coefficient of determination between predicted and actual ages surpasses both scAge and penalized regression.
2024-03-20 | GSE261769 | GEO
Project description:The evolution of spliceosomal introns remains poorly understood. Although many approaches have been used to infer intron evolution from the patterns of intron position conservation, the results to date have been contradictory. In this paper, we address the problem using a novel maximum likelihood method, which allows estimation of the frequency of intron insertion target sites, together with the rates of intron gain and loss. We analyzed the pattern of 10,044 introns (7,221 intron positions) in the conserved regions of 684 sets of orthologs from seven eukaryotes. We determined that there is an average of one target site per 11.86 base pairs (bp) (95% confidence interval, 9.27 to 14.39 bp). In addition, our results showed that: (i) overall intron gains are approximately 25% greater than intron losses, although specific patterns vary with time and lineage; (ii) parallel gains account for approximately 18.5% of shared intron positions; and (iii) reacquisition following loss accounts for approximately 0.5% of all intron positions. Our results should assist in resolving the long-standing problem of inferring the evolution of spliceosomal introns.
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Project description:Polyploidisation is a key source of diversification and speciation in plants. Most researchers consider sexual polyploidisation leading to unreduced gamete as its main origin. Unreduced gametes are useful in several crop breeding schemes. Their formation mechanism, i.e., First-Division Restitution (FDR) or Second-Division Restitution (SDR), greatly impacts the gametic and population structures and, therefore, the breeding efficiency. Previous methods to identify the underlying mechanism required the analysis of a large set of markers over large progeny. This work develops a new maximum-likelihood method to identify the unreduced gamete formation mechanism both at the population and individual levels using independent centromeric markers. Knowledge of marker-centromere distances greatly improves the statistical power of the comparison between the SDR and FDR hypotheses. Simulating data demonstrated the importance of selecting markers very close to the centromere to obtain significant conclusions at individual level. This new method was used to identify the meiotic restitution mechanism in nineteen mandarin genotypes used as female parents in triploid citrus breeding. SDR was identified for 85.3% of 543 triploid hybrids and FDR for 0.6%. No significant conclusions were obtained for 14.1% of the hybrids. At population level SDR was the predominant mechanisms for the 19 parental mandarins.
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Project description:Estimating fitness differences between allelic variants is a central goal of experimental evolution. Current methods for inferring such differences from allele frequency time series typically assume that the effects of selection can be described by a fixed selection coefficient. However, fitness is an aggregate of several components including mating success, fecundity, and viability. Distinguishing between these components could be critical in many scenarios. Here, we develop a flexible maximum likelihood framework that can disentangle different components of fitness from genotype frequency data, and estimate them individually in males and females. As a proof-of-principle, we apply our method to experimentally evolved cage populations of Drosophila melanogaster, in which we tracked the relative frequencies of a loss-of-function and wild-type allele of yellow This X-linked gene produces a recessive yellow phenotype when disrupted and is involved in male courtship ability. We find that the fitness costs of the yellow phenotype take the form of substantially reduced mating preference of wild-type females for yellow males, together with a modest reduction in the viability of yellow males and females. Our framework should be generally applicable to situations where it is important to quantify fitness components of specific genetic variants, including quantitative characterization of the population dynamics of CRISPR gene drives.
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Project description:The Global Navigation Satellite System is vulnerable to interference signals that can potentially disable the system, because the signal strength tends to be very weak. Interference such as jamming, which disables the receiver via excessively high signal strength in the satellite navigation frequency band, and spoofing, which induces the receiver to output erroneous position and time data via signals similar to actual navigation signals, disrupt satellite navigation systems. As the threat of interference is increasing, considerable research effort has been expended in an attempt to deal with it in various ways. Spoofing attacks are especially difficult to detect. This paper deals with a technique to detect a spoofing signal and to mitigate attacks on satellite navigation systems. The satellite navigation signal is influenced by the navigation satellite itself and errors due to environmental factors, and spoofing signal detection should be well reflected in the navigation signal. Especially, in the case of mobile receivers, it is not easy to detect a spoofing signal because the exact position of the receiver cannot be known. To detect a spoofing signal, additional hardware may be required; in some cases, heterogeneous sensors, such as inertial sensors, may be used. The technique introduced in this paper effectively discriminates spoofing signals based only on receiver measurements, without the need for additional devices. It generates test statistics based on the pseudorange, which is the measured value of the receiver position, and detects spoofing signals by setting the monitoring interval according to a "sliding window". Because the proposed method uses output data and measurements obtained from the receiver, it can be applied to general receivers at low cost.
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Project description:A penalized maximum likelihood method has been proposed as an important approach to the detection of epistatic quantitative trait loci (QTL). However, this approach is not optimal in two special situations: (1) closely linked QTL with effects in opposite directions and (2) small-effect QTL, because the method produces downwardly biased estimates of QTL effects. The present study aims to correct the bias by using correction coefficients and shifting from the use of a uniform prior on the variance parameter of a QTL effect to that of a scaled inverse chi-square prior. The results of Monte Carlo simulation experiments show that the improved method increases the power from 25 to 88% in the detection of two closely linked QTL of equal size in opposite directions and from 60 to 80% in the identification of QTL with small effects (0.5% of the total phenotypic variance). We used the improved method to detect QTL responsible for the barley kernel weight trait using 145 doubled haploid lines developed in the North American Barley Genome Mapping Project. Application of the proposed method to other shrinkage estimation of QTL effects is discussed.
| S-EPMC3313049 | biostudies-literature
Project description:The crystallographic reliability index [Formula: see text] is based on a method proposed more than two decades ago. Because its calculation is computationally expensive its use did not spread into the crystallographic community in favor of the cross-validation method known as [Formula: see text]. The importance of [Formula: see text] has grown beyond a pure validation tool. However, its application requires a sufficiently large dataset. In this work we assess the reliability of [Formula: see text] and we compare it with k-fold cross-validation, bootstrapping, and jackknifing. As opposed to proper cross-validation as realized with [Formula: see text], [Formula: see text] relies on a method of reducing bias from the structural model. We compare two different methods reducing model bias and question the widely spread notion that random parameter shifts are required for this purpose. We show that [Formula: see text] has as little statistical bias as [Formula: see text] with the benefit of a much smaller variance. Because the calculation of [Formula: see text] is based on the entire dataset instead of a small subset, it allows the estimation of maximum likelihood parameters even for small datasets. [Formula: see text] enables maximum likelihood-based refinement to be extended to virtually all areas of crystallographic structure determination including high-pressure studies, neutron diffraction studies, and datasets from free electron lasers.
| S-EPMC4517205 | biostudies-literature
Project description:A likelihood-based approach to density modification is developed that can be applied to a wide variety of cases where some information about the electron density at various points in the unit cell is available. The key to the approach consists of developing likelihood functions that represent the probability that a particular value of electron density is consistent with prior expectations for the electron density at that point in the unit cell. These likelihood functions are then combined with likelihood functions based on experimental observations and with others containing any prior knowledge about structure factors to form a combined likelihood function for each structure factor. A simple and general approach to maximizing the combined likelihood function is developed. It is found that this likelihood-based approach yields greater phase improvement in model and real test cases than either conventional solvent flattening and histogram matching or a recent reciprocal-space solvent-flattening procedure [Terwilliger (1999), Acta Cryst. D55, 1863-1871].
| S-EPMC2792768 | biostudies-literature
Project description:BACKGROUND: The abundance of new genomic data provides the opportunity to map the location of gene duplication and loss events on a species phylogeny. The first methods for mapping gene duplications and losses were based on a parsimony criterion, finding the mapping that minimizes the number of duplication and loss events. Probabilistic modeling of gene duplication and loss is relatively new and has largely focused on birth-death processes. RESULTS: We introduce a new maximum likelihood model that estimates the speciation and gene duplication and loss events in a gene tree within a species tree with branch lengths. We also provide an, in practice, efficient algorithm that computes optimal evolutionary scenarios for this model. We implemented the algorithm in the program DrML and verified its performance with empirical and simulated data. CONCLUSIONS: In test data sets, DrML finds optimal gene duplication and loss scenarios within minutes, even when the gene trees contain sequences from several hundred species. In many cases, these optimal scenarios differ from the lca-mapping that results from a parsimony gene tree reconciliation. Thus, DrML provides a new, practical statistical framework on which to study gene duplication.
| S-EPMC3044269 | biostudies-literature