scholarly journals BPscore: an effective metric for meaningful comparisons of structural chromosome segmentations

2018 ◽  
Author(s):  
Rafal Zaborowski ◽  
Bartek Wilczyński
Keyword(s):  
Experimental Data ◽  
Rapid Development ◽  
3D Structure ◽  
Jaccard Coefficient ◽  
Chromosome Conformation ◽  
Bipartite Matching ◽  
Chromosomal Structure ◽  
Topologically Associating Domains ◽  
Local Variant ◽  
Sound Metric

AbstractStudying the 3D structure of chromosomes is an emerging field flourishing in recent years because of rapid development of experimental approaches for studying chromosomal contacts. This has led to numerous studies providing results of segmentation of chromosome sequences of different species into so called Topologically Associating Domains (TADs). As the number of such studies grows steadily and many of them make claims about the perceived differences between TAD structures observed in different conditions, there is a growing need for good measures of similarity (or dissimilarity) between such segmentations. We provide here a BP score, which is a relatively simple distance metric based on the bipartite matching between two segmentations. In this paper, we provide the rationale behind choosing specifically this function and show its results on several different datasets, both simulated and experimental. We show that not only the BP score is a proper metric satisfying the triangle inequality, but that it is providing good granularity of scores for typical situations occuring between different TAD segmentations. We also introduce local variant of the BP metric and show that in actual comparisons between experimental datasets, the local BP score is correlating with the observed changes in gene expression and genome methylation. In summary, we consider the BP score a good foundation for analysing the dynamics of chromosome structures. The methodology we present in this work could be used by many researchers in their ongoing analyses making it a popular and useful tool.Author summaryMany researchers are interested in the chromosomal structure, its function and dynamics. Over the recent years, chromosome conformation capture (3C) methods have become the main source of experimental data on the subject and the Topologically Associating Domains (TADs) have become the de-facto standard unit of chromosomal structure. Many methods have been developed for TAD calling and the 3C experiments have been done in multiple conditions giving us a multitude of chromosomal segmentations describing the most atomic differences in chromosomal structure between conditions. Until now, such segmentations were compared mostly by very rough measures, such as the Jaccard coefficient or TAD overlaps or very general metrics like the variation of information coefficient. This has limited the researchers in the analysis of differential TAD segmentations, and practically prevented any proper analysis of TAD dynamics between conditions. Our approach has the potential to facilitate such analyses by providing researchers with mathematically sound metric that is designed specifically for the purpose and tested on both simulated and experimental data. Additionally, we provide a local variant of our measure that is a natural derivative of the BP score that can indicate which parts of the chromosomes are undergoing the most significant structural reorganizations.

scholarly journals An Overview of Multimodal Biometrics Using the Face and Ear

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Yichao Ma ◽  
Zengxi Huang ◽  
Xiaoming Wang ◽  
Kai Huang
Keyword(s):  
Rapid Development ◽  
3D Structure ◽  
Fusion Rule ◽  
Identification System ◽  
Multimodal Biometrics ◽  
Adaptive Fusion ◽  
The Face ◽  
Physiological Structure ◽  
Biometric Quality ◽  
Improved Accuracy

In the recent years, we have witnessed the rapid development of face recognition, though it is still plagued by variations such as facial expressions, pose, and occlusion. In contrast to the face, the ear has a stable 3D structure and is nearly unaffected by aging and expression changes. Both the face and ear can be captured from a distance and in a nonintrusive manner, which makes them applicable to a wider range of application domains. Together with their physiological structure and location, the ear can readily serve as supplement to the face for biometric recognition. It has been a trend to combine the face and ear to develop nonintrusive multimodal recognition for improved accuracy, robustness, and security. However, when either the face or the ear suffers from data degeneration, if the fusion rule is fixed or with inferior flexibility, a multimodal system may perform worse than the unimodal system using only the modality with better quality sample. The biometric quality-based adaptive fusion is an avenue to address this issue. In this paper, we present an overview of the literature about multimodal biometrics using the face and ear. All the approaches are classified into categories according to their fusion levels. In the end, we pay particular attention to an adaptive multimodal identification system, which adopts a general biometric quality assessment (BQA) method and dynamically integrates the face and ear via sparse representation. Apart from a refinement of the BQA and fusion weights selection, we extend the experiments for a more thorough evaluation by using more datasets and more types of image degeneration.

Towards A 3D Chromosome Shape Alphabet

2020 ◽  
Author(s):  
Carlos Soto ◽  
Darshan Bryner ◽  
Nicola Neretti ◽  
Anuj Srivastava
Keyword(s):  
Structural Biology ◽  
3D Structure ◽  
Proof Of Concept ◽  
3D Structures ◽  
3 Dimensional ◽  
Topologically Associating Domains ◽  
Independent Test ◽  
Sequence Logos ◽  
Shape Data

AbstractThe study of the 3-dimensional (3D) structure of chromosomes – the largest macromolecules in biology – is one of the most challenging to date in structural biology. Here, we develop a novel representation of chromosomes, as sequences of shape letters from a finite shape alphabet, which provides a compact and efficient way to analyze ensembles of chromosome shape data, akin to the analysis of texts in a language by using letters. We construct a Chromosome Shape Alphabet (CSA) from an ensemble of chromosome 3D structures inferred from Hi-C data – via SIMBA3D or other methods – by segmenting curves based on topologically associating domains (TADs) boundaries, and by clustering all TADs’ 3D structures into groups of similar shapes. The median shapes of these groups, with some pruning and processing, form the Chromosome Shape Letters (CSLs) of the alphabet. We provide a proof-of-concept for these CSLs by reconstructing independent test curves using only CSLs (and corresponding transformations) and comparing these reconstructions with the original curves. Finally, we demonstrate how CSLs can be used to summarize the variability of shapes in an ensemble of chromosome 3D structures using generalized sequence logos.

scholarly journals Spatial genome architecture and the emergence of malignancy

2020 ◽  
Vol 29 (R2) ◽  
pp. R197-R204 ◽  
Author(s):  
Adi Danieli ◽  
Argyris Papantonis
Keyword(s):  
Cell Cycle Progression ◽  
Specific Gene ◽  
Nucleotide Polymorphisms ◽  
Drug Target Discovery ◽  
Single Nucleotide ◽  
Chromosome Conformation ◽  
Chromosomal Structure ◽  
Coding Regions ◽  
Cell Type Specific ◽  
Cancer Types

Abstract Human chromosomes are large spatially and hierarchically structured entities, the integrity of which needs to be preserved throughout the lifespan of the cell and in conjunction with cell cycle progression. Preservation of chromosomal structure is important for proper deployment of cell type-specific gene expression programs. Thus, aberrations in the integrity and structure of chromosomes will predictably lead to disease, including cancer. Here, we provide an updated standpoint with respect to chromatin misfolding and the emergence of various cancer types. We discuss recent studies implicating the disruption of topologically associating domains, switching between active and inactive compartments, rewiring of promoter–enhancer interactions in malignancy as well as the effects of single nucleotide polymorphisms in non-coding regions involved in long-range regulatory interactions. In light of these findings, we argue that chromosome conformation studies may now also be useful for patient diagnosis and drug target discovery.

scholarly journals Effect of Weightlessness on the 3D Structure Formation and Physiologic Function of Human Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Zheng-Yang Chen ◽  
Song Guo ◽  
Bin-Bin Li ◽  
Nan Jiang ◽  
Ao Li ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Space Exploration ◽  
Rapid Development ◽  
3D Structure ◽  
Cell Aggregation ◽  
Migration Ability ◽  
Human Cancer Cells ◽  
Cell Cycle Inhibition ◽  
And Function

With the rapid development of modern medical technology and the deterioration of living environments, cancer, the most important disease that threatens human health, has attracted increasing concerns. Although remarkable achievements have been made in tumor research during the past several decades, a series of problems such as tumor metastasis and drug resistance still need to be solved. Recently, relevant physiological changes during space exploration have attracted much attention. Thus, space exploration might provide some inspiration for cancer research. Using on ground different methods in order to simulate microgravity, structure and function of cancer cells undergo many unique changes, such as cell aggregation to form 3D spheroids, cell-cycle inhibition, and changes in migration ability and apoptosis. Although numerous better experiments have been conducted on this subject, the results are not consistent. The reason might be that different methods for simulation have been used, including clinostats, random positioning machine (RPM) and rotating wall vessel (RWV) and so on. Therefore, we review the relevant research and try to explain novel mechanisms underlying tumor cell changes under weightlessness.

Highlighting of Critical Experimental Data for SOFC Modeling That is Missing From the Literature and Potential of N-IR Thermography for SOFC Study

2012 ◽  
Vol 9 (2) ◽  
Author(s):  
V. Lawlor
Keyword(s):  
Experimental Data ◽  
Solid Oxide Fuel Cells ◽  
Material Characterization ◽  
Electrochemical Reaction ◽  
Rapid Development ◽  
Hydrocarbon Fuel ◽  
Solid Oxide ◽  
Fundamental Operation ◽  
Ir Thermography ◽  
Fuel Reformation

Within the following brief is the researched conclusion that there is a lack of fundamental experimental data available to the scientific community detailing the temperature profile through the cathode/electrolyte/anode assembly section of Solid Oxide Fuel Cells (SOFC). Within these electrochemical reaction driving deceives, heat may be generated and diminished by several means. For example, heat is generally considered to be generated locally; as a result of the reactor’s fundamental operation. Furthermore, heat is generally considered to be generated and/or diminished, depending on the reforming method used, when the anode executes hydrocarbon fuel reformation. Not continually developing and/or utilizing novel experimental techniques, often developed for other fields, in order to provide fundamentally elucidating experimental data regarding SOFC operation is counter-intuitive. To date, the high temperature fuel cell field has not fully adopted the potential of thermography in order to study SOFC internal operation and indeed material characterization. This may be caused by the recent rapid development of the technology, which has reduced its cost while increasing its scope. This technical brief aims to highlight missing experimental data and suggest a technology and approach that may be able to address the issue.

scholarly journals Cohesin disrupts polycomb-dependent chromosome interactions

2019 ◽  
Author(s):  
JDP Rhodes ◽  
A Feldmann ◽  
B Hernández-Rodríguez ◽  
N Díaz ◽  
JM Brown ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Gene Repression ◽  
Chromosome Conformation ◽  
Regulate Gene Expression ◽  
Topologically Associating Domains ◽  
Chromosome Organisation ◽  
Regulate Gene

AbstractHow chromosome organisation is related to genome function remains poorly understood. Cohesin, loop-extrusion, and CTCF have been proposed to create structures called topologically associating domains (TADs) to regulate gene expression. Here, we examine chromosome conformation in embryonic stem cells lacking cohesin and find as in other cell types that cohesin is required to create TADs and regulate A/B compartmentalisation. However, in the absence of cohesin we identify a series of long-range chromosomal interactions that persist. These correspond to regions of the genome occupied by the polycomb repressive system, depend on PRC1, and we discover that cohesin counteracts these interactions. This disruptive activity is independent of CTCF and TADs, and regulates gene repression by the polycomb system. Therefore, in contrast to the proposal that cohesin creates structure in chromosomes, we discover a new role for cohesin in disrupting polycomb-dependent chromosome interactions to regulate gene expression.

scholarly journals Modeling Amantadine Treatment of Inuenza A Virus In Vitro

2021 ◽  
Author(s):  
Catherine A. A. Beauchemin ◽  
James J. McSharry ◽  
George L. Drusano ◽  
Jack T. Nguyen ◽  
Gregory T. Went ◽  
...  
Keyword(s):  
Experimental Data ◽  
Viral Infection ◽  
Mathematical Models ◽  
Influenza A ◽  
Mdck Cells ◽  
Rapid Development ◽  
Human Model ◽  
Parameter Estimates

We analyzed the dynamics of an influenza A/Albany/1/98 (H3N2) viral infection, using a set of mathematical models highlighting the differences between in vivo and in vitro infection. For example, we found that including virion loss due to cell entry was critical for the in vitro model but not for the in vivo model. Experiments were performed on influenza virus-infected MDCK cells in vitro inside a hollow-fiber (HF) system, which was used to continuously deliver the drug amantadine. The HF system captures the dynamics of an influenza infection, and is a controlled environment for producing experimental data which lend themselves well to mathematical modeling. The parameter estimates obtained from fitting our mathematical models to the HF experimental data are consistent with those obtained earlier for a primary infection in a human model. We found that influenza A/Albany/1/98 (H3N2) virions under normal experimental conditions at 37°C rapidly lose infectivity with a half-life of ~ 6.6 ± 0.2 h, and that the lifespan of productively infected MDCK cells is ~ 13 h. Finally, using our models we estimated that the maximum efficacy of amantadine in blocking viral infection is ~ 74%, and showed that this low maximum efficacy is likely due to the rapid development of drug resistance.

scholarly journals Data mining and machine learning methods for chromosome conformation data analysis

2019 ◽  
Author(s):  
◽  
Oluwatosin Oluwadare
Keyword(s):  
Data Analysis ◽  
Human Genome ◽  
Structure Prediction ◽  
Learning Algorithm ◽  
3D Structure ◽  
Three Dimensional ◽  
Gene Clusters ◽  
Research Field ◽  
Chromosome Conformation ◽  
Graphical Tool

Sixteen years after the sequencing of the human genome, the Human Genome Project (HGP), and 17 years after the introduction of Chromosome Conformation Capture (3C) technologies, three-dimensional (3-D) inference and big data remains problematic in the field of genomics, and specifically, in the field of 3C data analysis. Three-dimensional inference involves the reconstruction of a genome's 3D structure or, in some cases, ensemble of structures from contact interaction frequencies extracted from a variant of the 3C technology called the Hi-C technology. Further questions remain about chromosome topology and structure; enhancer-promoter interactions; location of genes, gene clusters, and transcription factors; the relationship between gene expression and epigenetics; and chromosome visualization at a higher scale, among others. In this dissertation, four major contributions are described, first, 3DMax, a tool for chromosome and genome 3-D structure prediction from H-C data using optimization algorithm, second, GSDB, a comprehensive and common repository that contains 3D structures for Hi-C datasets from novel 3D structure reconstruction tools developed over the years, third, ClusterTAD, a method for topological associated domains (TAD) extraction from Hi-C data using unsupervised learning algorithm. Finally, we introduce a tool called, GenomeFlow, a comprehensive graphical tool to facilitate the entire process of modeling and analysis of 3D genome organization. It is worth noting that GenomeFlow and GSDB are the first of their kind in the 3D chromosome and genome research field. All the methods are available as software tools that are freely available to the scientific community.

scholarly journals HBP: an integrative and flexible pipeline for the interaction analysis of Hi-C dataset

2016 ◽  
Author(s):  
Chao He ◽  
Ping Li ◽  
Minglei Shi ◽  
Yan Zhang ◽  
Bingyu Ye ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Molecular Mechanisms ◽  
Gene Expression Regulation ◽  
Interaction Analysis ◽  
Rapid Development ◽  
3D Structure ◽  
Biological Significance ◽  
Sequencing Data ◽  
Chromatin Interactions ◽  
Wide Range

AbstractBackgroundThe spatial organization of interphase chromatin in the nucleus play an important role in gene expression regulation and function. With the rapid development of revolutionized chromosome conformation capture technology and its genome-wide derivatives such as Hi-C, investigation of the genome folding becomes more efficient and convenient. How to robustly deal with these massive datasets and infer accurate 3D model and within-nucleus compartmentalization of chromosomes becomes a new challenge.ResultThe implemented pipeline HBP (Hi-C BED file analysis Pipeline) integrates existing pipelines focusing on individual steps of Hi-C data processing into an all-in-one package with adjustable parameters to infer the consensus 3D structure of genome from raw Hi-C sequencing data. What’s more, HBP could assign statistical confidence estimation for chromatin interactions, and clustering interaction loci according to enrichment tracks or topological structure automatically.ConclusionThe freely available HBP is an optimized and flexible pipeline for analyzing the folding of whole chromosome and interactions between some specific sites from the Hi-C raw sequencing reads to the partially processed datasets. The other complex genetic and epigenetic datasets from public sources such as GWAS, ENCODE consortiums etc. will also easily be integrated into HBP, hence the final output results of HBP could provide a comprehensive in-depth understanding for the specific chromatin interactions, potential molecular mechanisms and biological significance. We believe that HBP is a reliable tool for the rapidly analysis of Hi-C data and will be very useful for a wide range of researchers, particularly those who lack of background in computational biology. HBP is freely accessible at https://github.com/hechao0407/HBP/blob/master/HBP_1.0.tar.gz.

scholarly journals A chromosome folding intermediate at the condensin-to-cohesin transition during telophase

2019 ◽  
Author(s):  
Kristin Abramo ◽  
Anne-Laure Valton ◽  
Sergey V. Venev ◽  
Hakan Ozadam ◽  
A. Nicole Fox ◽  
...  
Keyword(s):  
Mitotic Chromosome ◽  
Chromatin Binding ◽  
Folding Intermediate ◽  
Binding Assays ◽  
Interphase Chromosome ◽  
Chromosome Conformation ◽  
Topologically Associating Domains ◽  
Late Telophase ◽  
Nested Loop ◽  
Inactive Chromatin

SummaryChromosome folding is extensively modulated as cells progress through the cell cycle. During mitosis, condensin complexes fold chromosomes in helically arranged nested loop arrays. In interphase, the cohesin complex generates loops that can be stalled at CTCF sites leading to positioned loops and topologically associating domains (TADs), while a separate process of compartmentalization drives the spatial segregation of active and inactive chromatin domains. We used synchronized cell cultures to determine how the mitotic chromosome conformation is transformed into the interphase state. Using Hi-C, chromatin binding assays, and immunofluorescence we show that by telophase condensin-mediated loops are lost and a transient folding intermediate devoid of most loops forms. By late telophase, cohesin-mediated CTCF-CTCF loops and positions of TADs start to emerge rapidly. Compartment boundaries are also established in telophase, but long-range compartmentalization is a slow process and proceeds for several hours after cells enter G1. Our results reveal the kinetics and order of events by which the interphase chromosome state is formed and identify telophase as a critical transition between condensin and cohesin driven chromosome folding.

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