scholarly journals Estimating DNA-DNA interaction frequency from Hi-C data at restriction-fragment resolution

2018 ◽  
Author(s):  
Christopher JF Cameron ◽  
Josée Dostie ◽  
Mathieu Blanchette
Keyword(s):  
Restriction Fragment ◽  
Cross Validation ◽  
Three Dimensional ◽  
Dna Interaction ◽  
Interaction Frequency ◽  
Chromosome Conformation ◽  
Restriction Fragments ◽  
Regulatory Interactions ◽  
Topologically Associating Domains ◽  
Validation Experiments

AbstractHi-C is a popular technique to map three-dimensional chromosome conformation. In principle, Hi-C’s resolution is only limited by the size of restriction fragments. However, insufficient sequencing depth forces researchers to artificially reduce the resolution of Hi-C matrices at a loss of biological interpretability. We present the Hi-C Interaction Frequency Inference (HIFI) algorithms that accurately estimate restriction-fragment resolution Hi-C matrices by exploiting dependencies between neighboring fragments. Cross-validation experiments and comparisons to 5C data and known regulatory interactions demonstrate HIFI’s superiority to existing approaches. In addition, HIFI’s restriction-fragment resolution reveals a new role for active regulatory regions in structuring topologically associating domains.Availability: https://github.com/BlanchetteLab/HIFI

scholarly journals Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF

2021 ◽  
Author(s):  
Abrar Aljahani ◽  
Peng Hua ◽  
Magdalena A. Karpinska ◽  
Kimberly Quililan ◽  
James O. J. Davies ◽  
...  
Keyword(s):  
Large Scale ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Interaction Data ◽  
Chromosome Conformation ◽  
Regulatory Interactions ◽  
Nano Scale ◽  
Topologically Associating Domains ◽  
Scale Structures ◽  
Local Insulation

Enhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated by cohesin and CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale and to what extent fine-scale regulatory interactions depend on loop extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, which has enabled us to generate the most detailed local interaction data to date and precisely investigate the effects of cohesin and CTCF depletion on chromatin architecture. Our data reveal that cis-regulatory elements have distinct internal nano-scale structures, within which local insulation is dependent on CTCF, but which are independent of cohesin. In contrast, we find that depletion of cohesin causes a subtle reduction in longer-range enhancer-promoter interactions and that CTCF depletion can cause rewiring of regulatory contacts. Together, our data show that loop extrusion is not essential for enhancer-promoter interactions, but contributes to their robustness and specificity and to precise regulation of gene expression.

scholarly journals Towards computer-aided severity assessment via deep neural networks for geographic and opacity extent scoring of SARS-CoV-2 chest X-rays

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. Wong ◽  
Z. Q. Lin ◽  
L. Wang ◽  
A. G. Chung ◽  
B. Shen ◽  
...  
Keyword(s):  
Neural Networks ◽  
Monte Carlo ◽  
Lung Disease ◽  
Disease Severity ◽  
Deep Neural Networks ◽  
Cross Validation ◽  
X Rays ◽  
Computer Aided ◽  
Monte Carlo Cross Validation ◽  
Validation Experiments

AbstractA critical step in effective care and treatment planning for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause for the coronavirus disease 2019 (COVID-19) pandemic, is the assessment of the severity of disease progression. Chest x-rays (CXRs) are often used to assess SARS-CoV-2 severity, with two important assessment metrics being extent of lung involvement and degree of opacity. In this proof-of-concept study, we assess the feasibility of computer-aided scoring of CXRs of SARS-CoV-2 lung disease severity using a deep learning system. Data consisted of 396 CXRs from SARS-CoV-2 positive patient cases. Geographic extent and opacity extent were scored by two board-certified expert chest radiologists (with 20+ years of experience) and a 2nd-year radiology resident. The deep neural networks used in this study, which we name COVID-Net S, are based on a COVID-Net network architecture. 100 versions of the network were independently learned (50 to perform geographic extent scoring and 50 to perform opacity extent scoring) using random subsets of CXRs from the study, and we evaluated the networks using stratified Monte Carlo cross-validation experiments. The COVID-Net S deep neural networks yielded R$$^2$$ 2 of $$0.664 \pm 0.032$$ 0.664 ± 0.032 and $$0.635 \pm 0.044$$ 0.635 ± 0.044 between predicted scores and radiologist scores for geographic extent and opacity extent, respectively, in stratified Monte Carlo cross-validation experiments. The best performing COVID-Net S networks achieved R$$^2$$ 2 of 0.739 and 0.741 between predicted scores and radiologist scores for geographic extent and opacity extent, respectively. The results are promising and suggest that the use of deep neural networks on CXRs could be an effective tool for computer-aided assessment of SARS-CoV-2 lung disease severity, although additional studies are needed before adoption for routine clinical use.

scholarly journals Interclass Interference Suppression in Multi-Class Problems

2021 ◽  
Vol 11 (1) ◽  
pp. 450
Author(s):  
Jinfu Liu ◽  
Mingliang Bai ◽  
Na Jiang ◽  
Ran Cheng ◽  
Xianling Li ◽  
...  
Keyword(s):  
Classification Accuracy ◽  
Cross Validation ◽  
Selection Process ◽  
Interference Suppression ◽  
Generalization Ability ◽  
Suppression Effect ◽  
Binary Classifiers ◽  
The One ◽  
Fold Cross Validation ◽  
Validation Experiments

Multi-classifiers are widely applied in many practical problems. But the features that can significantly discriminate a certain class from others are often deleted in the feature selection process of multi-classifiers, which seriously decreases the generalization ability. This paper refers to this phenomenon as interclass interference in multi-class problems and analyzes its reason in detail. Then, this paper summarizes three interclass interference suppression methods including the method based on all-features, one-class classifiers and binary classifiers and compares their effects on interclass interference via the 10-fold cross-validation experiments in 14 UCI datasets. Experiments show that the method based on binary classifiers can suppress the interclass interference efficiently and obtain the best classification accuracy among the three methods. Further experiments were done to compare the suppression effect of two methods based on binary classifiers including the one-versus-one method and one-versus-all method. Results show that the one-versus-one method can obtain a better suppression effect on interclass interference and obtain better classification accuracy. By proposing the concept of interclass inference and studying its suppression methods, this paper significantly improves the generalization ability of multi-classifiers.

The eruptive regime of mass-transfer-driven Rayleigh–Marangoni convection

2016 ◽  
Vol 791 ◽  
Author(s):  
Thomas Köllner ◽  
Karin Schwarzenberger ◽  
Kerstin Eckert ◽  
Thomas Boeck
Keyword(s):  
Concentration Distribution ◽  
Marangoni Convection ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Boussinesq Equations ◽  
Navier Stokes ◽  
Flow Structures ◽  
Rayleigh Convection ◽  
Marangoni Effects ◽  
Validation Experiments

The transfer of an alcohol, 2-propanol, from an aqueous to an organic phase causes convection due to density differences (Rayleigh convection) and interfacial tension gradients (Marangoni convection). The coupling of the two types of convection leads to short-lived flow structures called eruptions, which were reported in several previous experimental studies. To unravel the mechanism underlying these patterns, three-dimensional direct numerical simulations and corresponding validation experiments were carried out and compared with each other. In the simulations, the Navier–Stokes–Boussinesq equations were solved with a plane interface that couples the two layers including solutal Marangoni effects. Our simulations show excellent agreement with the experimentally observed patterns. On this basis, the origin of the eruptions is explained by a two-step process in which Rayleigh convection continuously produces a concentration distribution that triggers an opposing Marangoni flow.

scholarly journals Reorganization of chromosome architecture in replicative cellular senescence

2016 ◽  
Vol 2 (2) ◽  
pp. e1500882 ◽  
Author(s):  
Steven W. Criscione ◽  
Marco De Cecco ◽  
Benjamin Siranosian ◽  
Yue Zhang ◽  
Jill A. Kreiling ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Structural Model ◽  
Three Dimensional ◽  
Chromatin Accessibility ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
Topologically Associated Domains ◽  
Chromosomal Architecture ◽  
Fundamental Biological Process ◽  
3D Architecture

Replicative cellular senescence is a fundamental biological process characterized by an irreversible arrest of proliferation. Senescent cells accumulate a variety of epigenetic changes, but the three-dimensional (3D) organization of their chromatin is not known. We applied a combination of whole-genome chromosome conformation capture (Hi-C), fluorescence in situ hybridization, and in silico modeling methods to characterize the 3D architecture of interphase chromosomes in proliferating, quiescent, and senescent cells. Although the overall organization of the chromatin into active (A) and repressive (B) compartments and topologically associated domains (TADs) is conserved between the three conditions, a subset of TADs switches between compartments. On a global level, the Hi-C interaction matrices of senescent cells are characterized by a relative loss of long-range and gain of short-range interactions within chromosomes. Direct measurements of distances between genetic loci, chromosome volumes, and chromatin accessibility suggest that the Hi-C interaction changes are caused by a significant reduction of the volumes occupied by individual chromosome arms. In contrast, centromeres oppose this overall compaction trend and increase in volume. The structural model arising from our study provides a unique high-resolution view of the complex chromosomal architecture in senescent cells.

scholarly journals Technologies to study spatial genome organization: beyond 3C

2019 ◽  
Author(s):  
Nadine Übelmesser ◽  
Argyris Papantonis
Keyword(s):  
Genome Organization ◽  
Nuclear Organization ◽  
Three Dimensional ◽  
Nuclear Space ◽  
Chromosome Conformation ◽  
Novel Variants ◽  
Cell Processes ◽  
Systematic Biases ◽  
And Function ◽  
Spatial Genome Organization

Abstract The way that chromatin is organized in three-dimensional nuclear space is now acknowledged as a factor critical for the major cell processes, like transcription, replication and cell division. Researchers have been armed with new molecular and imaging technologies to study this structure-to-function link of genomes, spearheaded by the introduction of the ‘chromosome conformation capture’ technology more than a decade ago. However, this technology is not without shortcomings, and novel variants and orthogonal approaches are being developed to overcome these. As a result, the field of nuclear organization is constantly fueled by methods of increasing resolution and/or throughput that strive to eliminate systematic biases and increase precision. In this review, we attempt to highlight the most recent advances in technology that promise to provide novel insights on how chromosomes fold and function.

scholarly journals OnTAD: hierarchical domain structure reveals the divergence of activity among TADs and boundaries

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Lin An ◽  
Tao Yang ◽  
Jiahao Yang ◽  
Johannes Nuebler ◽  
Guanjue Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Domain Structure ◽  
High Frequency ◽  
Spatial Organization ◽  
Structural Units ◽  
Regulatory Interactions ◽  
Link Type ◽  
Topologically Associating Domains

AbstractThe spatial organization of chromatin in the nucleus has been implicated in regulating gene expression. Maps of high-frequency interactions between different segments of chromatin have revealed topologically associating domains (TADs), within which most of the regulatory interactions are thought to occur. TADs are not homogeneous structural units but appear to be organized into a hierarchy. We present OnTAD, an optimized nested TAD caller from Hi-C data, to identify hierarchical TADs. OnTAD reveals new biological insights into the role of different TAD levels, boundary usage in gene regulation, the loop extrusion model, and compartmental domains. OnTAD is available at https://github.com/anlin00007/OnTAD.

scholarly journals The DLO Hi-C Tool for Digestion-Ligation-Only Hi-C Chromosome Conformation Capture Data Analysis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 289 ◽  
Author(s):  
Ping Hong ◽  
Hao Jiang ◽  
Weize Xu ◽  
Da Lin ◽  
Qian Xu ◽  
...  
Keyword(s):  
Target Genes ◽  
High Efficiency ◽  
New Technology ◽  
Three Dimensional ◽  
Large Data ◽  
Regulatory Elements ◽  
Chromosome Conformation Capture ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
3D Genome

It is becoming increasingly important to understand the mechanism of regulatory elements on target genes in long-range genomic distance. 3C (chromosome conformation capture) and its derived methods are now widely applied to investigate three-dimensional (3D) genome organizations and gene regulation. Digestion-ligation-only Hi-C (DLO Hi-C) is a new technology with high efficiency and cost-effectiveness for whole-genome chromosome conformation capture. Here, we introduce the DLO Hi-C tool, a flexible and versatile pipeline for processing DLO Hi-C data from raw sequencing reads to normalized contact maps and for providing quality controls for different steps. It includes more efficient iterative mapping and linker filtering. We applied the DLO Hi-C tool to different DLO Hi-C datasets and demonstrated its ability in processing large data with multithreading. The DLO Hi-C tool is suitable for processing DLO Hi-C and in situ DLO Hi-C datasets. It is convenient and efficient for DLO Hi-C data processing.

scholarly journals The three-dimensional genome organization of Drosophila melanogaster through data integration

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Qingjiao Li ◽  
Harianto Tjong ◽  
Xiao Li ◽  
Ke Gong ◽  
Xianghong Jasmine Zhou ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Data Integration ◽  
Genome Organization ◽  
Genome Structure ◽  
Three Dimensional ◽  
Structural Features ◽  
Embryonic Cells ◽  
Data Types ◽  
Chromosome Conformation ◽  
Topological Domains

Abstract Background Genome structures are dynamic and non-randomly organized in the nucleus of higher eukaryotes. To maximize the accuracy and coverage of three-dimensional genome structural models, it is important to integrate all available sources of experimental information about a genome’s organization. It remains a major challenge to integrate such data from various complementary experimental methods. Here, we present an approach for data integration to determine a population of complete three-dimensional genome structures that are statistically consistent with data from both genome-wide chromosome conformation capture (Hi-C) and lamina-DamID experiments. Results Our structures resolve the genome at the resolution of topological domains, and reproduce simultaneously both sets of experimental data. Importantly, this data deconvolution framework allows for structural heterogeneity between cells, and hence accounts for the expected plasticity of genome structures. As a case study we choose Drosophila melanogaster embryonic cells, for which both data types are available. Our three-dimensional genome structures have strong predictive power for structural features not directly visible in the initial data sets, and reproduce experimental hallmarks of the D. melanogaster genome organization from independent and our own imaging experiments. Also they reveal a number of new insights about genome organization and its functional relevance, including the preferred locations of heterochromatic satellites of different chromosomes, and observations about homologous pairing that cannot be directly observed in the original Hi-C or lamina-DamID data. Conclusions Our approach allows systematic integration of Hi-C and lamina-DamID data for complete three-dimensional genome structure calculation, while also explicitly considering genome structural variability.

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