Prediction of Molecular Properties Using Molecular Topographic Map.
Ontology highlight
ABSTRACT:
SUBMITTER: Yoshimori A
PROVIDER: S-EPMC8348331 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: Numerous methods have been developed over the last decade to predict allelic identity at unobserved loci between pairs of chromosome segments along the genome. These loci are often unobserved positions tested for the presence of quantitative trait loci (QTL). The main objective of this study was to understand from a theoretical standpoint the relation between linkage disequilibrium (LD) and allelic identity prediction when using haplotypes for fine mapping of QTL. In addition, six allelic identity predictors (AIP) were also compared in this study to determine which one performed best in theory and application. RESULTS: A criterion based on a simple measure of matrix distance was used to study the relation between LD and allelic identity prediction when using haplotypes. The consistency of this criterion with the accuracy of QTL localization, another criterion commonly used to compare AIP, was evaluated on a set of real chromosomes. For this set of chromosomes, the criterion was consistent with the mapping accuracy of a simulated QTL with either low or high effect. As measured by the matrix distance, the best AIP for QTL mapping were those that best captured LD between a tested position and a QTL. Moreover the matrix distance between a tested position and a QTL was shown to decrease for some AIP when LD increased. However, the matrix distance for AIP with continuous predictions in the [0,1] interval was algebraically proven to decrease less rapidly up to a lower bound with increasing LD in the simplest situations, than the discrete predictor based on identity by state between haplotypes (IBS hap), for which there was no lower bound. The expected LD between haplotypes at a tested position and alleles at a QTL is a quantity that increases naturally when the tested position gets closer to the QTL. This behavior was demonstrated with pig and unrelated human chromosomes. CONCLUSIONS: When the density of markers is high, and therefore LD between adjacent loci can be assumed to be high, the discrete predictor IBS hap is recommended since it predicts allele identity correctly when taking LD into account.
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Project description:Discovering new drugs for disease treatment is challenging, requiring a multidisciplinary effort as well as time, and resources. With a view to improving hit discovery and lead compound identification, machine learning (ML) approaches are being increasingly used in the decision-making process. Although a number of ML-based studies have been published, most studies only report fragments of the wider range of bioactivities wherein each model typically focuses on a particular disease. This study introduces FP-MAP, an extensive atlas of fingerprint-based prediction models that covers a diverse range of activities including neglected tropical diseases (caused by viral, bacterial and parasitic pathogens) as well as other targets implicated in diseases such as Alzheimer's. To arrive at the best predictive models, performance of ≈4,000 classification/regression models were evaluated on different bioactivity data sets using 12 different molecular fingerprints. The best performing models that achieved test set AUC values of 0.62-0.99 have been integrated into an easy-to-use graphical user interface that can be downloaded from https://gitlab.com/vishsoft/fpmap.
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Project description:Geographical research using historical maps has progressed considerably as the digitalization of topological maps across years provides valuable data and the advancement of AI machine learning models provides powerful analytic tools. Nevertheless, analysis of historical maps based on supervised learning can be limited by the laborious manual map annotations. In this work, we propose a semi-supervised learning method that can transfer the annotation of maps across years and allow map comparison and anthropogenic studies across time. Our novel two-stage framework first performs style transfer of topographic map across years and versions, and then supervised learning can be applied on the synthesized maps with annotations. We investigate the proposed semi-supervised training with the style-transferred maps and annotations on four widely-used deep neural networks (DNN), namely U-Net, fully-convolutional network (FCN), DeepLabV3, and MobileNetV3. The best performing network of U-Net achieves [Formula: see text] and [Formula: see text] trained on style-transfer synthesized maps, which indicates that the proposed framework is capable of detecting target features (bridges) on historical maps without annotations. In a comprehensive comparison, the [Formula: see text] of U-Net trained on Contrastive Unpaired Translation (CUT) generated dataset ([Formula: see text]) achieves 57.3 % than the comparative score ([Formula: see text]) of the least valid configuration (MobileNetV3 trained on CycleGAN synthesized dataset). We also discuss the remaining challenges and future research directions.
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Project description:BackgroundAssessing the nucleosome-forming potential of specific DNA sequences is important for understanding complex chromatin organization. Methods for predicting nucleosome positioning include bioinformatics and biophysical approaches. An advantage of bioinformatics methods, which are based on in vivo nucleosome maps, is the use of natural sequences that may contain previously unknown elements involved in nucleosome positioning in vivo. The accuracy of such prediction attempts reflects the genomic coordinate resolution of the nucleosome maps applied. Nucleosome maps are constructed using micrococcal nuclease digestion followed by high-throughput sequencing (MNase-seq). However, as MNase has a strong preference for A/T-rich sequences, MNase-seq may not be appropriate for this purpose. In addition to MNase-seq-based maps, base pair-resolution chemical maps of in vivo nucleosomes from three different species (budding and fission yeasts, and mice) are currently available. However, these chemical maps have yet to be integrated into publicly available computational methods.ResultsWe developed a Bioconductor package (named nuCpos) to demonstrate the superiority of chemical maps in predicting nucleosome positioning. The accuracy of chemical map-based prediction in rotational settings was higher than that of the previously developed MNase-seq-based approach. With our method, predicted nucleosome occupancy reasonably matched in vivo observations and was not affected by A/T nucleotide frequency. Effects of genetic alterations on nucleosome positioning that had been observed in living yeast cells could also be predicted. nuCpos calculates individual histone binding affinity (HBA) scores for given 147-bp sequences to examine their suitability for nucleosome formation. We also established local HBA as a new parameter to predict nucleosome formation, which was calculated for 13 overlapping nucleosomal DNA subsequences. HBA and local HBA scores for various sequences agreed well with previous in vitro and in vivo studies. Furthermore, our results suggest that nucleosomal subsegments that are disfavored in different rotational settings contribute to the defined positioning of nucleosomes.ConclusionsOur results demonstrate that chemical map-based statistical models are beneficial for studying nucleosomal DNA features. Studies employing nuCpos software can enhance understanding of chromatin regulation and the interpretation of genetic alterations and facilitate the design of artificial sequences.
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Project description:BackgroundMost genomic prediction applications in animal breeding use genotypes with tens of thousands of single nucleotide polymorphisms (SNPs). However, modern sequencing technologies and imputation algorithms can generate ultra-high-density genotypes (including millions of SNPs) at an affordable cost. Empirical studies have not produced clear evidence that using ultra-high-density genotypes can significantly improve prediction accuracy. However, (whole-genome) prediction accuracy is not very informative about the ability of a model to capture the genetic signals from specific genomic regions. To address this problem, we propose a simple methodology that detects chromosome regions for which a specific model (e.g., single-step genomic best linear unbiased prediction (ssGBLUP)) may fail to fully capture the genetic signal present in such segments-a phenomenon that we refer to as signal leakage. We propose to detect regions with evidence of signal leakage by testing the association of residuals from a pedigree or a genomic model with SNP genotypes. We discuss how this approach can be used to map regions with signals that are poorly captured by a model and to identify strategies to fix those problems (e.g., using a different prior or increasing marker density). Finally, we explored the proposed approach to scan for signal leakage of different models (pedigree-based, ssGBLUP, and various Bayesian models) applied to growth-related phenotypes (average daily gain and backfat thickness) in pigs.ResultsWe report widespread evidence of signal leakage for pedigree-based models. Including a percentage of animals with SNP data in ssGBLUP reduced the extent of signal leakage. However, local peaks of missed signals remained in some regions, even when all animals were genotyped. Using variable selection priors solves leakage points that are caused by excessive shrinkage of marker effects. Nevertheless, these models still miss signals in some regions due to low linkage disequilibrium between the SNPs on the array used and causal variants. Thus, we discuss how such problems could be addressed by adding sequence SNPs from those regions to the prediction model.ConclusionsResidual single-marker regression analysis is a simple approach that can be used to detect regional genomic signals that are poorly captured by a model and to indicate ways to fix such problems.
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