DeepTACT: predicting 3D chromatin contacts via bootstrapping deep learning.
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ABSTRACT:
SUBMITTER: Li W
PROVIDER: S-EPMC6547469 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
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Project description:Chromatin contacts between regulatory elements are of crucial importance for the interpretation of transcriptional regulation and the understanding of disease mechanisms. However, existing computational methods mainly focus on the prediction of interactions between enhancers and promoters, leaving enhancer-enhancer (E-E) interactions not well explored. In this work, we develop a novel deep learning approach, named Enhancer-enhancer contacts prediction (EnContact), to predict E-E contacts using genomic sequences as input. We statistically demonstrated the predicting ability of EnContact using training sets and testing sets derived from HiChIP data of seven cell lines. We also show that our model significantly outperforms other baseline methods. Besides, our model identifies finer-mapping E-E interactions from region-based chromatin contacts, where each region contains several enhancers. In addition, we identify a class of hub enhancers using the predicted E-E interactions and find that hub enhancers tend to be active across cell lines. We summarize that our EnContact model is capable of predicting E-E interactions using features automatically learned from genomic sequences.
| S-EPMC6746221 | biostudies-literature
Project description:BackgroundAccurate prediction of inter-residue contacts of a protein is important to calculating its tertiary structure. Analysis of co-evolutionary events among residues has been proved effective in inferring inter-residue contacts. The Markov random field (MRF) technique, although being widely used for contact prediction, suffers from the following dilemma: the actual likelihood function of MRF is accurate but time-consuming to calculate; in contrast, approximations to the actual likelihood, say pseudo-likelihood, are efficient to calculate but inaccurate. Thus, how to achieve both accuracy and efficiency simultaneously remains a challenge.ResultsIn this study, we present such an approach (called clmDCA) for contact prediction. Unlike plmDCA using pseudo-likelihood, i.e., the product of conditional probability of individual residues, our approach uses composite-likelihood, i.e., the product of conditional probability of all residue pairs. Composite likelihood has been theoretically proved as a better approximation to the actual likelihood function than pseudo-likelihood. Meanwhile, composite likelihood is still efficient to maximize, thus ensuring the efficiency of clmDCA. We present comprehensive experiments on popular benchmark datasets, including PSICOV dataset and CASP-11 dataset, to show that: i) clmDCA alone outperforms the existing MRF-based approaches in prediction accuracy. ii) When equipped with deep learning technique for refinement, the prediction accuracy of clmDCA was further significantly improved, suggesting the suitability of clmDCA for subsequent refinement procedure. We further present a successful application of the predicted contacts to accurately build tertiary structures for proteins in the PSICOV dataset.ConclusionsComposite likelihood maximization algorithm can efficiently estimate the parameters of Markov Random Fields and can improve the prediction accuracy of protein inter-residue contacts.
| S-EPMC6821021 | biostudies-literature
Project description:BackgroundRecent advances in genome analysis have established that chromatin has preferred 3D conformations, which bring distant loci into contact. Identifying these contacts is important for us to understand possible interactions between these loci. This has motivated the creation of the Hi-C technology, which detects long-range chromosomal interactions. Distance geometry-based algorithms, such as ChromSDE and ShRec3D, have been able to utilize Hi-C data to infer 3D chromosomal structures. However, these algorithms, being matrix-based, are space- and time-consuming on very large datasets. A human genome of 100 kilobase resolution would involve ∼30,000 loci, requiring gigabytes just in storing the matrices.ResultsWe propose a succinct representation of the distance matrices which tremendously reduces the space requirement. We give a complete solution, called SuperRec, for the inference of chromosomal structures from Hi-C data, through iterative solving the large-scale weighted multidimensional scaling problem.ConclusionsSuperRec runs faster than earlier systems without compromising on result accuracy. The SuperRec package can be obtained from http://www.cs.cityu.edu.hk/~shuaicli/SuperRec .
| S-EPMC6456969 | biostudies-literature
Project description:MOTIVATION:Alternative splicing generates multiple isoforms from a single gene, greatly increasing the functional diversity of a genome. Although gene functions have been well studied, little is known about the specific functions of isoforms, making accurate prediction of isoform functions highly desirable. However, the existing approaches to predicting isoform functions are far from satisfactory due to at least two reasons: (i) unlike genes, isoform-level functional annotations are scarce. (ii) The information of isoform functions is concealed in various types of data including isoform sequences, co-expression relationship among isoforms, etc. RESULTS:In this study, we present a novel approach, DIFFUSE (Deep learning-based prediction of IsoForm FUnctions from Sequences and Expression), to predict isoform functions. To integrate various types of data, our approach adopts a hybrid framework by first using a deep neural network (DNN) to predict the functions of isoforms from their genomic sequences and then refining the prediction using a conditional random field (CRF) based on co-expression relationship. To overcome the lack of isoform-level ground truth labels, we further propose an iterative semi-supervised learning algorithm to train both the DNN and CRF together. Our extensive computational experiments demonstrate that DIFFUSE could effectively predict the functions of isoforms and genes. It achieves an average area under the receiver operating characteristics curve of 0.840 and area under the precision-recall curve of 0.581 over 4184 GO functional categories, which are significantly higher than the state-of-the-art methods. We further validate the prediction results by analyzing the correlation between functional similarity, sequence similarity, expression similarity and structural similarity, as well as the consistency between the predicted functions and some well-studied functional features of isoform sequences. AVAILABILITY AND IMPLEMENTATION:https://github.com/haochenucr/DIFFUSE. SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.
| S-EPMC6612874 | biostudies-other
Project description:The packaging of DNA inside a nucleus shows complex structure stabilized by a host of DNA-bound factors. Both the distribution of these factors and the contacts between different genomic locations of the DNA can now be measured on a genome-wide scale. This has advanced the development of models aimed at predicting the conformation of DNA given only the locations of bound factors-the chromatin folding problem. Here we present a maximum-entropy model that is able to predict a contact map representation of structure given a sequence of bound factors. Non-local effects due to the sequence neighborhood around contacting sites are found to be important for making accurate predictions. Lastly, we show that the model can be used to infer a sequence of bound factors given only a measurement of structure. This opens up the possibility for efficiently predicting sequence regions that may play a role in generating cell-type specific structural differences.
| S-EPMC5814105 | biostudies-literature
Project description:MotivationPromoter-centered chromatin interactions, which include promoter-enhancer (PE) and promoter-promoter (PP) interactions, are important to decipher gene regulation and disease mechanisms. The development of next-generation sequencing technologies such as promoter capture Hi-C (pcHi-C) leads to the discovery of promoter-centered chromatin interactions. However, pcHi-C experiments are expensive and thus may be unavailable for tissues/cell types of interest. In addition, these experiments may be underpowered due to insufficient sequencing depth or various artifacts, which results in a limited finding of interactions. Most existing computational methods for predicting chromatin interactions are based on in situ Hi-C and can detect chromatin interactions across the entire genome. However, they may not be optimal for predicting promoter-centered chromatin interactions.ResultsWe develop a supervised multi-modal deep learning model, which utilizes a comprehensive set of features such as genomic sequence, epigenetic signal, anchor distance, evolutionary features and DNA structural features to predict tissue/cell type-specific PE and PP interactions. We further extend the deep learning model in a multi-task learning and a transfer learning framework and demonstrate that the proposed approach outperforms state-of-the-art deep learning methods. Moreover, the proposed approach can achieve comparable prediction performance using predefined biologically relevant tissues/cell types compared to using all tissues/cell types in the pretraining especially for predicting PE interactions. The prediction performance can be further improved by using computationally inferred biologically relevant tissues/cell types in the pretraining, which are defined based on the common genes in the proximity of two anchors in the chromatin interactions.Availability and implementationhttps://github.com/lichen-lab/DeepPHiC.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9825766 | biostudies-literature
Project description:In recent years, major advances have been made in various chromosome conformation capture technologies to further satisfy the needs of researchers for high-quality, high-resolution contact interactions. Discriminating the loops from genome-wide contact interactions is crucial for dissecting three-dimensional(3D) genome structure and function. Here, we present a deep learning method to predict genome-wide chromatin loops, called DLoopCaller, by combining accessible chromatin landscapes and raw Hi-C contact maps. Some available orthogonal data ChIA-PET/HiChIP and Capture Hi-C were used to generate positive samples with a wider contact matrix which provides the possibility to find more potential genome-wide chromatin loops. The experimental results demonstrate that DLoopCaller effectively improves the accuracy of predicting genome-wide chromatin loops compared to the state-of-the-art method Peakachu. Moreover, compared to two of most popular loop callers, such as HiCCUPS and Fit-Hi-C, DLoopCaller identifies some unique interactions. We conclude that a combination of chromatin landscapes on the one-dimensional genome contributes to understanding the 3D genome organization, and the identified chromatin loops reveal cell-type specificity and transcription factor motif co-enrichment across different cell lines and species.
| S-EPMC9581407 | biostudies-literature
Project description:Automated species classification from 3D point clouds is still a challenge. It is, however, an important task for laser scanning-based forest inventory, ecosystem models, and to support forest management. Here, we tested the performance of an image classification approach based on convolutional neural networks (CNNs) with the aim to classify 3D point clouds of seven tree species based on 2D representation in a computationally efficient way. We were particularly interested in how the approach would perform with artificially increased training data size based on image augmentation techniques. Our approach yielded a high classification accuracy (86%) and the confusion matrix revealed that despite rather small sample sizes of the training data for some tree species, classification accuracy was high. We could partly relate this to the successful application of the image augmentation technique, improving our result by 6% in total and 13, 14, and 24% for ash, oak and pine, respectively. The introduced approach is hence not only applicable to small-sized datasets, it is also computationally effective since it relies on 2D instead of 3D data to be processed in the CNN. Our approach was faster and more accurate when compared to the point cloud-based "PointNet" approach.
| S-EPMC7902704 | biostudies-literature
Project description:MotivationInter-protein (interfacial) contact prediction is very useful for in silico structural characterization of protein-protein interactions. Although deep learning has been applied to this problem, its accuracy is not as good as intra-protein contact prediction.ResultsWe propose a new deep learning method GLINTER (Graph Learning of INTER-protein contacts) for interfacial contact prediction of dimers, leveraging a rotational invariant representation of protein tertiary structures and a pretrained language model of multiple sequence alignments. Tested on the 13th and 14th CASP-CAPRI datasets, the average top L/10 precision achieved by GLINTER is 54% on the homodimers and 52% on all the dimers, much higher than 30% obtained by the latest deep learning method DeepHomo on the homodimers and 15% obtained by BIPSPI on all the dimers. Our experiments show that GLINTER-predicted contacts help improve selection of docking decoys.Availability and implementationThe software is available at https://github.com/zw2x/glinter. The datasets are available at https://github.com/zw2x/glinter/data.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC8796373 | biostudies-literature
Project description:Understanding 3D genome structure requires high throughput, genome-wide approaches. However, assays for all vs. all chromatin interaction mapping are expensive and time consuming, which severely restricts their usage for large-scale mutagenesis screens or for mapping the impact of sequence variants. Computational models sophisticated enough to grasp the determinants of chromatin folding provide a unique window into the functional determinants of 3D genome structure as well as the effects of genome variation. A chromatin interaction predictor should work at the base pair level but also incorporate large-scale genomic context to simultaneously capture the large scale and intricate structures of chromatin architecture. Similarly, to be a flexible and generalisable approach it should also be applicable to data it has not been explicitly trained on. To develop a model with these properties, we designed a deep neuronal network (deepC) that utilizes transfer learning to accurately predict chromatin interactions from DNA sequence at megabase scale. The model generalizes well to unseen chromosomes and works across cell types, Hi-C data resolutions and a range of sequencing depths. DeepC integrates DNA sequence context on an unprecedented scale, bridging the different levels of resolution from base pairs to TADs. We demonstrate how this model allows us to investigate sequence determinants of chromatin folding at genome-wide scale and to predict the importance of regulatory elements and the impact of sequence variations.
2020-07-08 | GSE137436 | GEO