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作者： Andrew Dhawan

Competing endogenous RNA (ceRNA) molecules have emerged as key players in regulating gene expression, increasing the complexity of the range of possible dynamics within a cell. The actions of competing RNA typically are sponging behaviors, in a manner that fine-tunes gene expression, but there are particular network structures that may show destabilization due to ceRNA interactions. In this chapter, we discuss how these interactions can be modeled and probed from a mathematical, first-principles perspective. less

关键词： Mathematical Modeling Approximate Bayesian Computation Python programming language MicroRNAs Non-coding RNA Pseudogene Network modeling ceRNAs

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Protocol for Epistasis Detection with Machine Learning Using GenEpi Package

Protocol for Epistasis Detection with Machine Learning Using...

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作者： Olutomilayo Olayemi Petinrin Ka-Chun Wong

To develop medical treatments and prevention, the association between disease and genetic variants needs to be identified. The main goal of genome-wide association study (GWAS) is to discover the underlying reason for vulnerability to disease and utilize this knowledge for the development of prevention and treatment against these diseases. Given the methods available to address the scientific problems involved in the search for epistasis, there is not any standard for detecting epistasis, and this remains a problem due to limited statistical power. The GenEpi package is a Python package that uses a two-level workflow machine learning model to detect within-gene and cross-gene epistasis. This protocol chapter shows the usage of GenEpi with example data. The package uses a three-step procedure to reduce dimensionality, select the within-gene epistasis, and select the cross-gene epistasis. The package also provides a medium to build prediction models with the combination of genetic features and environmental influences.

关键词： Machine Learning Genome-Wide Association Study Gene Prediction Python programming language Homo sapiens Epistasis Genotype SNP Phenotype GenEpi

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Computational Antigen Discovery for Eukaryotic Pathogens Using

Computational Antigen Discovery for Eukaryotic Pathogens Usi...

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作者： Stephen J. Goodswen Paul J. Kennedy John T. Ellis

Bioinformatics programs have been developed that exploit informative signals encoded within protein sequences to predict protein characteristics. Unfortunately, there is no program as yet that can predict whether a protein will induce a protective immune response to a pathogen. Nonetheless, predicting those pathogen proteins most likely from those least likely to induce an immune response is feasible when collectively using predicted protein characteristics. Vacceed is a computational pipeline that manages different standalone bioinformatics programs to predict various protein characteristics, which offer supporting evidence on whether a protein is secreted or membrane -associated. A set of machine learning algorithms predicts the most likely pathogen proteins to induce an immune response given the supporting evidence. This chapter provides step by step descriptions of how to configure and operate Vacceed for a eukaryotic pathogen of the user’s choice. less

关键词： Machine Learning programming language Vacceed In silico vaccine discovery Computational antigen discovery Eukaryotic pathogen

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High-resolution structural and functional deep brain imaging using adaptive optics three-photon microscopy

High-resolution structural and functional deep brain imaging...

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作者： Lina Streich Juan Carlos Boffi Ling Wang Khaleel Alhalaseh Matteo Barbieri Ronja Rehm Senthilkumar Deivasigamani Cornelius T. Gross Amit Agarwal Robert Prevedel

Multiphoton microscopy has become a powerful tool with which to visualize the morphology and function of neural cells and circuits in the intact mammalian brain. However, tissue scattering, optical aberrations and motion artifacts degrade the imaging performance at depth. Here we describe a minimally invasive intravital imaging methodology based on three-photon excitation, indirect adaptive optics (AO) and active electrocardiogram gating to advance deep-tissue imaging. Our modal-based, sensorless AO approach is robust to low signal-to-noise ratios as commonly encountered in deep scattering tissues such as the mouse brain, and permits AO correction over large axial fields of view. We demonstrate near-diffraction-limited imaging of deep cortical spines and (sub)cortical dendrites up to a depth of 1.4 mm (the edge of the mouse CA1 hippocampus). In addition, we show applications to deep-layer calcium imaging of astrocytes, including fibrous astrocytes that reside in the highly scattering corpus callosum. less

关键词： Calcium Imaging Fluorescence Microscopy Multiphoton Microscopy Microscopy Brain Slice Preparation Electrocardiogram MATLAB Affinity Chromatography Titration Real-time PCR Surgery In Vivo Imaging Machine Learning Adaptive optics Intravital Microscopy programming language Glial biology

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3D Printing of Functionally Graded Films by Controlling Process Parameters

3D Printing of Functionally Graded Films by Controlling Proc...

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作者： Alessandra Bonfanti Loris Domenicale Atul Bhaskar

Scaffolds are often used in bioengineering to replace damaged tissues. They promote cell ingrowth and provide mechanical support until cells regenerate. Such scaffolds are often made using the additive manufacturing process, given its ability to create complex shapes, affordability, and the potential for patient-specific solutions. The success of the implant is closely related to the match of the scaffold mechanical properties to those of the host tissue. Many biological tissues show properties that vary in space. Therefore, the aim is to manufacture materials with variable properties, commonly referred to as functionally graded materials. Here we present a novel technique used to manufacture porous films with functionally graded properties using 3D printers. Such an approach exploits the control of a process parameter, without any hardware modification. The mechanical properties of the manufactured films have been experimentally tested and analytically characterized. less

关键词： Extrusion programming language Additive manufacturing Functionally graded material Graded films G-code Process parameter

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Estimating Global Methylation and Erasure Using Low-Coverage Whole-Genome Bisulfite SequencingBisulfite sequencing (BS-Seq) (WGBS Whole-genome bisulfite sequencing (WGBS) )

Estimating Global Methylation and Erasure Using Low-Coverage...

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作者： Oscar Ortega-Recalde Julian R. Peat Donna M. Bond Timothy A. Hore

Whole-genome bisulfite sequencing (WGBS) is a popular method for characterizing cytosine methylation because it is fully quantitative and has base-pair resolution. While WGBS is prohibitively expensive for experiments involving many samples, low-coverage WGBS can accurately determine global methylation and erasure at similar cost to high-performance liquid chromatography (HPLC) or enzyme-linked immunosorbent assays (ELISA). Moreover, low-coverage WGBS has the capacity to distinguish between methylation in different cytosine contexts (e.g., CG, CHH, and CHG), can tolerate low-input material (<100 cells), and can detect the presence of overrepresented DNA originating from mitochondria or amplified ribosomal DNA. In addition to describing a WGBS library construction and quantitation approach, here we detail computational methods to predict the accuracy of low-coverage WGBS using empirical bootstrap samplers and theoretical estimators similar to those used in election polling. Using examples, we further demonstrate how non-independent sampling of cytosines can alter the precision of error calculation and provide methods to improve this. less

关键词： Bisulfite Sequencing Library Preparation HPLC High-Throughput Sequencing Cell Lysis DNA Purification DNA Extraction PCR programming language DNA methylation Epigenetics Methylation erasure Post-bisulfite adaptor tagging Bootstrap sampling Asymptotic estimator

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High-Resolution ChIP-MNaseChIP-MNase Mapping of Nucleosome Positions at Selected Genomic Loci and Alleles

High-Resolution ChIP-MNaseChIP-MNase Mapping of Nucleosome P...

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作者： Dominic van Essen Agata Oruba Simona Saccani

The positioning of nucleosomes regulates the accessibility of genomic DNA and can impact the activities of functional elements. Nucleosome positioning is highly consistent at each genomic location in any particular cell-type, but can vary in an orchestrated fashion between different cell-types and between genomic loci according to their activities. Here, we describe a technique—“ChIP-MNase” (chromatin immunoprecipitation linked to micrococcal nuclease mapping)—to determine nucleosome positions at chosen sets of genomic features that can be defined by their molecular composition and recovered by chromatin immunoprecipitation. ChIP-MNase enables high-resolution analysis of nucleosome positioning at genomic regions-of-interest and can allow differential analysis of alleles undergoing distinct molecular processes. less

关键词： ChIP Assay Cell And Tissue Culture Cross-linking Titration Capillary Electrophoresis (CE) Sonication Freeze-thaw Method Immunoprecipitation High-Throughput Sequencing PCR Capillary Gel Electrophoresis Library Preparation Genome Visualization DNA Purification Gel Electrophoresis Bowtie Data analysis bedtools programming language Nucleosomes Chromatin Chromatin accessibility Micrococcal nuclease

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Programmers do not favor lambda expressions for concurrent object-oriented code

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EMPIRICAL SOFTWARE ENGINEERING 2019年第1期24卷 103-138页

作者： Nielebock, Sebastian Heumueller, Robert Ortmeier, Frank Otto von Guericke Univ Chair Software Engn Fac Comp Sci Magdeburg Germany

Lambda expressions have long been state-of-the-art in the functional programming paradigm. Especially with regard to the use of higher-order functions, they provide developers with a means of defining predicate or projection functions locally, which greatly increases the comprehensibility of the resulting source code. This benefit has motivated language designers to also incorporate lambda expressions into object-oriented (OO) programming languages. In particular, they are claimed to facilitate concurrent programming. One likely reason for this assumption is their purity: pure lambda expressions are free of side effects, and therefore cannot cause, e.g., race conditions. In this paper, we present the first empirical analysis of whether or not this claim is true for OO projects. For this purpose, we investigated the application of lambda expressions in 2923 open-source projects, implemented in one of the most common OO programming languages: C#, C++, and Java. We present three major findings. First, the majority of lambda expressions are not applied in concurrent code and most concurrent code does not make use of lambda expressions. Second, for all three of the languages, we observed that developers compromise their code by applying a significantly higher number of impure, capturing lambda expressions, which are capable of causing race conditions. Finally, we explored further use cases of lambda expressions and found out that testing, algorithmic implementation, and UI are far more common use-cases for the application of lambda expressions. Our results encourage to investigate in more detail the reasons that hinder programmers to apply lambda expressions in concurrent programming and to support developers, e.g., by providing automatic refactorings.

关键词： Lambda expression Concurrency Object-orientation programming language

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Lightweight Named Object: An ICN-Based Abstraction for IoT Device programming and Management

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IEEE INTERNET OF THINGS JOURNAL 2019年第3期6卷 5029-5039页

作者： Bracciale, Lorenzo Loreti, Pierpaolo Detti, Andrea Paolillo, Riccardo Melazzi, Nicola Blefari Univ Roma Tor Vergata Dept Elect Engn I-00133 Rome Italy Consorzio Nazl Interuniv Telecomunicaz UDR Roma Tor Vergata I-00133 Rome Italy

The expected dramatic growth of connected things raises the issue of how to efficiently organize them, in order to monitor and manage functions and interactions. Information centric networking (ICN) is a communication paradigm that provides content-oriented functionality in the network and at the network level, including content routing, caching, multicast, mobility, data-centric security, and a flexible namespace. Thus, it is a viable solution for supporting Internet of Things (IoT) services without requiring any centralized entity. In this paper, we introduce the lightweight named object solution: a convenient way to represent physical IoT objects in a derived name space, exploiting ICN. We show that this abstraction can: 1) increase the programming simplicity;2) offer extended functionality, such as augmentation and upgrading, to cope with the "software erosion," and 3) implement a common interaction logic involving mutual function invocation. We present some proof-of-concept implementations of the proposed abstraction dealing with challenging IoT test cases;we also carry out a performance evaluation in a simulated network scenario.

关键词： Augmentation data-centric security distributed objects information centric networking (ICN) Internet of Things (IoT) named data networking (NDN) naming programming language

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Chromatin Immunoprecipitation Followed by Next-Generation Sequencing (ChIP-Seq) Analysis in Ewing Sarcoma

Chromatin Immunoprecipitation Followed by Next-Generation Se...

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作者： Gwenneg Kerdivel Valentina Boeva

ChIP-seq is the method of choice for profiling protein–DNA interactions, and notably for characterizing the landscape of transcription factor binding and histone modifications. This technique has been widely used to study numerous aspects of tumor biology and led to the development of several promising cancer therapies. In Ewing sarcoma research, ChIP-seq provided important insights into the mechanism of action of the major oncogenic fusion protein EWSR1-FLI1 and related epigenetic and transcriptional changes. In this chapter, we provide a detailed pipeline to analyze ChIP-seq experiments from the preprocessing of raw data to tertiary analysis of detected binding sites. We also advise on best practice to prepare tumor samples prior to sequencing. less

关键词： ChIP-seq ChIP Assay Peak Calling Library Preparation Immunoprecipitation Variant Calling PCR Genome Visualization RNA-seq Statistical Calculation Genome Assembly Genomics programming language Transcription factors Binding sites Histone modifications Ewing sarcoma Motif analysis

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