MOLKERN: A library of software components for molecular modeling programs

The library of software components MOLKERN is designed to construct efficient programs (with linear computational complexity) for modeling, optimization, and analysis of spatial structures of proteins, cofactors, ligands, and their complexes and computation of their physical properties. The interactions between atoms and molecules are taken into account within the force field method. The library is realized in C++ using static polymorphism technology. The library utilizes STL and BOOST libraries and contains a number of software components for parallel computation using the MPI technology. The library can be used under Windows and Linux.     

An improved de novo genome assembly of the common marmoset genome yields improved contiguity and increased mapping rates of sequence data

Background

DNA methylation is a crucial epigenomic mechanism in various biological processes. Using whole-genome bisulfite sequencing (WGBS) technology, methylated cytosine sites can be revealed at the single nucleotide level. However, the WGBS data analysis process is usually complicated and challenging.

Results

To alleviate the associated difficulties, we integrated the WGBS data processing steps and downstream analysis into a two-phase approach. First, we set up the required tools in Galaxy and developed workflows to calculate the methylation level from raw WGBS data and generate a methylation status summary, the mtable. This computation environment is wrapped into the Docker container image DocMethyl, which allows users to rapidly deploy an executable environment without tedious software installation and library dependency problems. Next, the mtable files were uploaded to the web server EpiMOLAS_web to link with the gene annotation databases that enable rapid data retrieval and analyses.

Conclusion

To our knowledge, the EpiMOLAS framework, consisting of DocMethyl and EpiMOLAS_web, is the first approach to include containerization technology and a web-based system for WGBS data analysis from raw data processing to downstream analysis. EpiMOLAS will help users cope with their WGBS data and also conduct reproducible analyses of publicly available data, thereby gaining insights into the mechanisms underlying complex biological phenomenon. The Galaxy Docker image DocMethyl is available at https://hub.docker.com/r/lsbnb/docmethyl/.

EpiMOLAS_web is publicly accessible at http://symbiosis.iis.sinica.edu.tw/epimolas/.

     

A spatio-temporal mining approach towards summarizing and analyzing protein folding trajectories

This paper presents a software library, nicknamed BATS, for some basic sequence analysis tasks. Namely, local alignments, via approximate string matching, and global alignments, via longest common subsequence and alignments with affine and concave gap cost functions. Moreover, it also supports filtering operations to select strings from a set and establish their statistical significance, via z-score computation. None of the algorithms is new, but although they are generally regarded as fundamental for sequence analysis, they have not been implemented in a single and consistent software package, as we do here. Therefore, our main contribution is to fill this gap between algorithmic theory and practice by providing an extensible and easy to use software library that includes algorithms for the mentioned string matching and alignment problems. The library consists of C/C++ library functions as well as Perl library functions. It can be interfaced with Bioperl and can also be used as a stand-alone system with a GUI. The software is available at http://www.math.unipa.it/~raffaele/BATS/ under the GNU GPL.     

Media optimization for SHuffle T7 Escherichia coli expressing SUMO-Lispro proinsulin by response surface methodology

Background

The present study intends to optimize the processing technology for the wine-processing of Rhizoma Coptidis, using alkaloids as indicators.

Method

In the present study, the Box–Behnken design method was adopted to optimize the processing technology for Rhizoma Coptidis, using the alkaloid component quantities as the index. 100 g of Rhizoma Coptidis slices and 12.5 g of Rhizoma Coptidis wine were used. After full mixing, box-Behnken design method was used to optimize the processing time, processing temperature and processing time of coptis chinensis by taking alkaloid content as index. After mixing well, these components were fried in a container at 125 °C for 6 min and exhibited good parallelism.

Results

The content of alkaloids in coptis chinensis was the highest after roasting at 125 °C for 6 min. The characteristic components were berberine hydrochloride, and the relative content was about 15.96%. And showed good parallelism. The effective components of Rhizoma Coptidis were primarily alkaloids.

Conclusion

The optimized processing technology for Rhizoma Coptidis is good.

     

AUDIO COMPUTERS—THEORY OF OPERATION AND GUIDELINES FOR SELECTION OF SYSTEMS AND COMPONENTS

ABSTRACT

Computers are available that can store, synthesize and replay sounds using digital technology. I describe the major components of audio computers, the principles of digital sound acquisition and playback, and information and caveats for scientists interested in acquiring an audio computer system for their own use. A tutorial on analog filter application is also included as well as a diagnostic procedure and a buyer's check list.     

Parameterization of mechanistic models from qualitative data using an efficient optimal scaling approach

Quantitative dynamical models facilitate the understanding of biological processes and the prediction of their dynamics. These models usually comprise unknown parameters, which have to be inferred from experimental data. For quantitative experimental data, there are several methods and software tools available. However, for qualitative data the available approaches are limited and computationally demanding. Here, we consider the optimal scaling method which has been developed in statistics for categorical data and has been applied to dynamical systems. This approach turns qualitative variables into quantitative ones, accounting for constraints on their relation. We derive a reduced formulation for the optimization problem defining the optimal scaling. The reduced formulation possesses the same optimal points as the established formulation but requires less degrees of freedom. Parameter estimation for dynamical models of cellular pathways revealed that the reduced formulation improves the robustness and convergence of optimizers. This resulted in substantially reduced computation times. We implemented the proposed approach in the open-source Python Parameter EStimation TOolbox (pyPESTO) to facilitate reuse and extension. The proposed approach enables efficient parameterization of quantitative dynamical models using qualitative data.

     

Synthesis of Polyaminooligonucleotides and Their Combinatorial Libraries

Abstract

A synthesis of phosphoramidites of 2′-deoxyadenosine and 2′-deoxyguanosine carrying a protected spermine moiety at N-6 and N-2 positions respectively is described. An approach to analyse properties of polyaminooligonucleotides using their synthetic combinatorial libraries is described and discussed. A synthesis of a polyaminooligonucleotide combinatorial library was carried out and the analysis of the library clearly showed that the presence of spermine moieties in oligodeoxyribonucleotides increases stability of their complexes.     

Establishment of genomic library technology mediated by non-homologous end joining mechanism in Yarrowia lipolytica

Genomic variants libraries are conducive to obtain dominant strains with desirable phenotypic traits. The non-homologous end joining (NHEJ), which enables foreign DNA fragments to be randomly integrated into different chromosomal sites, shows prominent capability in genomic libraries construction. In this study, we established an efficient NHEJ-mediated genomic library technology in Yarrowia lipolytica through regulation of NHEJ repair process, employment of defective Ura marker and optimization of iterative transformations, which enhanced genes integration efficiency by 4.67, 22.74 and 1.87 times, respectively. We further applied this technology to create high lycopene producing strains by multi-integration of heterologous genes of CrtE, CrtB and CrtI, with 23.8 times higher production than rDNA integration through homologous recombination (HR). The NHEJ-mediated genomic library technology also achieved random and scattered integration of loxP and vox sites, with the copy number up to 65 and 53, respectively, creating potential for further application of recombinase mediated genome rearrangement in Y. lipolytica. This work provides a high-efficient NHEJ-mediated genomic library technology, which enables random and scattered genomic integration of multiple heterologous fragments and rapid generation of diverse strains with superior phenotypes within 96 h. This novel technology also lays an excellent foundation for the development of other genetic technologies in Y. lipolytica.

     

Isolation of Functional RNA from Periderm Tissue of Potato Tubers and Sweet Potato Storage Roots

A reliable and efficient protocol is given for the isolation of mRNA from the periderm of potato tubers and sweet potato storage roots. The method relies on a urea-based lysis buffer and lithium chloride to concentrate total RNA away from most of the cytoplasmic components and to prevent oxidation of phenolic complexes. To enhance the physical separation of the RNA from other macromolecular components, the RNA fraction was incubated in the presence of the cationic surfactant Catrimox-14. Poly(A)⁺ mRNA was separated from total RNA and other contaminants by using Promega's MagneSphere technology. The mRNA was suitable for cDNA library construction and RNA fingerprinting.     

Blue light emission spectra of popular mobile devices: The extent of user protection against melatonin suppression by built-in screen technology and light filtering software systems

ABSTRACT

Blue light, with wavelengths shorter than 440–450 nm, is the most energetic radiation of the visible spectrum for the human eye, and its possible multiple effects on the human nervous and other systems have become a line of research by many investigators. The use of mobile devices whose screens emit various amounts of blue light is common nowadays. This study evaluated the efficiency of the blue light screen and control software technologies of eight different mobile devices. Emitted screen spectra of the different mobile devices according to different conditions of blue light emission software control were obtained using a spectrograph, and the derived spectra were compared with the melatonin suppression action spectrum. The amount of blue light emission and predicted melatonin suppression varied according to the unique software control and screen technology of each device. AMOLED screen technology, compared with other screen technologies, achieved better control of blue light emission. The effect of blue light filters depends on the screen technology; however, the melatonin suppression index of mobile devices is not reduced sufficiently by the use of blue light-attenuating software.     

A COMPUTER-BASED TECHNIQUE FOR THE QUANTITATIVE ANALYSIS OF ANIMAL SOUNDS

ABSTRACT

The method usually used to identify different sounds or divisions of sounds is to compare sonagrams visually. There have been some attempts to reduce the subjectivity and increase the repeatability of this approach, for example by tracing the sonagrams onto paper and examining the areas of overlap and mismatch, the use of multi-variate statistics and digitising tablets. Digital recording of sounds has allowed sounds to be input directly into computers which can be used to display sounds and facilitate measurement. To date there has been little attempt at their use for analysis. We outline a series of programs which have been developed to compare statistically any unit of a sound with a pre-recorded library of similar units. The creation of such a library allows the rapid and objective categorisation of large numbers of sounds. These programs have been used to analyse songs recorded from wrens Troglodytes troglodytes and house crickets Acheta domesticus. Potential applications of this software to the field of bioacoustic investigation are discussed.     

Marathon: An Open Source Software Library for the Analysis of Markov-Chain Monte Carlo Algorithms

We present the software library marathon, which is designed to support the analysis of sampling algorithms that are based on the Markov-Chain Monte Carlo principle. The main application of this library is the computation of properties of so-called state graphs, which represent the structure of Markov chains. We demonstrate applications and the usefulness of marathon by investigating the quality of several bounding methods on four well-known Markov chains for sampling perfect matchings and bipartite graphs. In a set of experiments, we compute the total mixing time and several of its bounds for a large number of input instances. We find that the upper bound gained by the famous canonical path method is often several magnitudes larger than the total mixing time and deteriorates with growing input size. In contrast, the spectral bound is found to be a precise approximation of the total mixing time.     

Process simulation and gate-to-gate life cycle assessment of hydrometallurgical refractory gold concentrate processing

Purpose

Currently, almost all cyanide-free gold leaching processes are still in the development stage. Proactively investigating their environmental impacts prior to commercialization is of utmost importance. In this study, a detailed refractory gold concentrate process simulation with mass and energy balance was built for state-of-the-art technology with (i) pressure oxidation followed by cyanidation and, compared to alternative cyanide-free technology, with (ii) pressure oxidation followed by halogen leaching. Subsequently, the simulated mass balance was used as life cycle inventory data in order to evaluate the environmental impacts of the predominant cyanidation process and a cyanide-free alternative.

Methods

The environmental indicators for each scenario are based on the mass balance produced with HSC Sim steady-state simulation. The simulated mass balances were evaluated to identify the challenges in used technologies. The HSC Sim software is compatible with the GaBi LCA software, where LCI data from HSC-Sim is directly exported to. The simulation produces a consistent life cycle inventory (LCI). In GaBi LCA software, the environmental indicators of global warming potential (GWP), acidification potential (AP), terrestrial eutrophication potential (EP), and water depletion (Water) are estimated.

Results and discussion

The life cycle assessment revealed that the GWP for cyanidation was 10.1 t CO₂-e/kg Au, whereas the halogen process indicated a slightly higher GWP of 12.6 t CO₂-e/kg Au. The difference is partially explained by the fact that the footprint is calculated against produced units of Au; total recovery by the halogen leaching route for gold was only 87.3%, whereas the cyanidation route could extract as much as 98.5% of gold. The addition of a second gold recovery unit to extract gold also from the washing water in the halogen process increased gold recovery up to 98.5%, decreasing the GWP of the halogen process to 11.5 t CO₂-e/kg Au. However, both evaluated halogen processing scenarios indicated a slightly higher global warming potential when compared to the dominating cyanidation technology.

Conclusions

The estimated environmental impacts predict that the development-stage cyanide-free process still has some challenges compared to cyanidation; as in the investigated scenarios, the environmental impacts were generally higher for halogen leaching. Further process improvements, for example in the form of decreased moisture in the feed for halide leaching, and the adaptation of in situ gold recovery practices in chloride leaching may give the cyanide-free processing options a competitive edge.

     

Developing a Model Driven Approach for engineering applications based on mOSAIC

In many scientific and engineering areas there are emerging software services available over the Web. The reason for deploying such services in the Cloud is either to reduce the operational costs or to support the peaks in their usage profiles. The algorithms employed in such services are usually result of a long term research and technology development work, so it is beneficial to reuse those critical application parts when developing new Cloud applications. This paper investigates the possibilities to introduce a Model Driven Architecture (MDA) for the Cloud computing domain, which would support composition, customization, flexibility, maintenance and reusability of Cloud application components in the particular case of scientific and engineering applications. The underlying middleware technology of choice is the mOSAIC Platform as a Service (PaaS) solution. This choice is motivated by the fact that in mOSAIC a Cloud application consists of loosely coupled components, which are either generic and provide for key resource types needed by an application (computation, storage, communication) or custom made, e.g. based on existing legacy software. The MDA approach is illustrated through the design and operation of an application for analysis of structures under static loading. It is shown that a relatively simple design can be used to address two application bottlenecks: the varying number of users and the computational complexity of the given problem. The design reduces the necessary application development efforts and the key components can be reused for similar applications.     

PD5: A General Purpose Library for Primer Design Software

Background

Complex PCR applications for large genome-scale projects require fast, reliable and often highly sophisticated primer design software applications. Presently, such applications use pipelining methods to utilise many third party applications and this involves file parsing, interfacing and data conversion, which is slow and prone to error. A fully integrated suite of software tools for primer design would considerably improve the development time, the processing speed, and the reliability of bespoke primer design software applications.

Results

The PD5 software library is an open-source collection of classes and utilities, providing a complete collection of software building blocks for primer design and analysis. It is written in object-oriented C⁺⁺ with an emphasis on classes suitable for efficient and rapid development of bespoke primer design programs. The modular design of the software library simplifies the development of specific applications and also integration with existing third party software where necessary. We demonstrate several applications created using this software library that have already proved to be effective, but we view the project as a dynamic environment for building primer design software and it is open for future development by the bioinformatics community. Therefore, the PD5 software library is published under the terms of the GNU General Public License, which guarantee access to source-code and allow redistribution and modification.

Conclusions

The PD5 software library is downloadable from Google Code and the accompanying Wiki includes instructions and examples: http://code.google.com/p/primer-design     

元江普通野生稻叶片cDNA文库的构建及部分基因片段分析

首次利用SMARTTM技术构建了中国普通野生稻中最原始类型——元江普通野生稻生长旺盛时期叶片的cDNA文库。该cDNA文库未扩增和扩增后的滴度分别为1.1×10⁶ pfu/mL和3.98×10⁷ pfu/mL, 重组率为91%, 插入片段大小为500～2 000 bp。测定的部分cDNA序列进行BLAST比较, 发现这些cDNA片段与日本晴栽培稻同源性很高, 达到98%以上。本研究为进一步分析这些cDNA片段的结构、功能和探讨元江普通野生稻在栽培稻演化中的地位奠定了基础。     

GITAR: An Open Source Tool for Analysis and Visualization of Hi-C Data

Interactions between chromatin segments play a large role in functional genomic assays and developments in genomic interaction detection methods have shown interacting topological domains within the genome. Among these methods, Hi-C plays a key role. Here, we present the Genome Interaction Tools and Resources (GITAR), a software to perform a comprehensive Hi-C data analysis, including data preprocessing, normalization, and visualization, as well as analysis of topologically-associated domains (TADs). GITAR is composed of two main modules: (1) HiCtool, a Python library to process and visualize Hi-C data, including TAD analysis; and (2) processed data library, a large collection of human and mouse datasets processed using HiCtool. HiCtool leads the user step-by-step through a pipeline, which goes from the raw Hi-C data to the computation, visualization, and optimized storage of intra-chromosomal contact matrices and TAD coordinates. A large collection of standardized processed data allows the users to compare different datasets in a consistent way, while saving time to obtain data for visualization or additional analyses. More importantly, GITAR enables users without any programming or bioinformatic expertise to work with Hi-C data. GITAR is publicly available at http://genomegitar.org as an open-source software.     

落叶型大丽轮枝菌T-DNA插入突变体库的构建

采用ATMT技术建立大丽轮枝菌落叶型菌株XJ2008菌株的T-DNA插入突变体文库,共获得6 043个突变体。从中随机挑选104个突变体,以野生型XJ2008菌株为参照,评价其致病性、菌落生长速率、分生孢子及微菌核的产生能力等。结果表明,有12.5%的突变体丧失产孢能力,4.8%的突变体的生长速率显著减慢,8.7%的突变体的生长速率显著加快,12.5%的突变体丧失产生微菌核的能力,47.1%的突变体的致病性显著低于野生型菌株XJ2008,且突变体2-736、2-740、2-745的病情指数分别约为野生型菌株XJ2008的0.184、0.168和0.197倍。该突变体库突变体遗传稳定性好,性状多样性丰富。     

mrMLM v4.0.2:An R Platform for Multi-locus Genome-wide Association Studies

Previous studies have reported that some important loci are missed in single-locus genome-wide association studies (GWAS), especially because of the large phenotypic error in field experiments. To solve this issue, multi-locus GWAS methods have been recommended. However, only a few software packages for multi-locus GWAS are available. Therefore, we developed an R software named mrMLM v4.0.2. This software integrates mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB, pKWmEB, and ISIS EM-BLASSO methods developed by our lab. There are four components in mrMLM v4.0.2, including dataset input, parameter setting, software running, and result output. The fread function in data.table is used to quickly read datasets, especially big datasets, and the doParallel package is used to conduct parallel computation using multiple CPUs. In addition, the graphical user interface software mrMLM.GUI v4.0.2, built upon Shiny, is also available. To confirm the correctness of the aforementioned programs, all the methods in mrMLM v4.0.2 and three widely-used methods were used to analyze real and simulated datasets. The results confirm the superior performance of mrMLM v4.0.2 to other methods currently available. False positive rates are effectively controlled, albeit with a less stringent significance threshold. mrMLM v4.0.2 is publicly available at BioCode (https://bigd.big.ac.cn/biocode/tools/BT007077) or R (https://cran.r-project.org/web/packages/mrMLM.GUI/index.html) as an open-source software.