scholarly journals Identifying highly-penetrant disease causal mutations using next generation sequencing: Guide to whole process

2014 ◽  
Author(s):  
Mesut Erzurumluoglu
Keyword(s):  
Complex Disorders ◽  
Mendelian Disorders ◽  
Whole Process ◽  
Analysis Process ◽  
Technological Advances ◽  
File Formats ◽  
Wide Range ◽  
Human Disorders ◽  
Analysis Schema ◽  
Generation Sequencing

Recent technological advances have created challenges for geneticists and a need to adapt to a wide range of new bioinformatics tools and an expanding wealth of publicly available data (e.g. mutation databases, software). This wide range of methods and a diversity of file formats used in sequence analysis is a significant issue, with a considerable amount of time spent before anyone can even attempt to analyse the genetic basis of human disorders. Another point to consider is although many possess "just enough" knowledge to analyse their data, they do not make full use of the tools and databases that are available and also do not know how their data was created. The primary aim of this review is to document some of the key approaches and provide an analysis schema to make the analysis process more efficient and reliable in the context of discovering highly penetrant causal mutations/genes. This review will also compare the methods used to identify highly penetrant variants when data is obtained from consanguineous individuals as opposed to non-consanguineous; and when Mendelian disorders are analysed as opposed to common-complex disorders.

scholarly journals Identifying Highly Penetrant Disease Causal Mutations Using Next Generation Sequencing: Guide to Whole Process

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
A. Mesut Erzurumluoglu ◽  
Santiago Rodriguez ◽  
Hashem A. Shihab ◽  
Denis Baird ◽  
Tom G. Richardson ◽  
...  
Keyword(s):  
Complex Disorders ◽  
Mendelian Disorders ◽  
Whole Process ◽  
Analysis Process ◽  
Technological Advances ◽  
File Formats ◽  
Wide Range ◽  
Human Disorders ◽  
Analysis Schema ◽  
Generation Sequencing

Recent technological advances have created challenges for geneticists and a need to adapt to a wide range of new bioinformatics tools and an expanding wealth of publicly available data (e.g., mutation databases, and software). This wide range of methods and a diversity of file formats used in sequence analysis is a significant issue, with a considerable amount of time spent before anyone can even attempt to analyse the genetic basis of human disorders. Another point to consider that is although many possess “just enough” knowledge to analyse their data, they do not make full use of the tools and databases that are available and also do not fully understand how their data was created. The primary aim of this review is to document some of the key approaches and provide an analysis schema to make the analysis process more efficient and reliable in the context of discovering highly penetrant causal mutations/genes. This review will also compare the methods used to identify highly penetrant variants when data is obtained from consanguineous individuals as opposed to nonconsanguineous; and when Mendelian disorders are analysed as opposed to common-complex disorders.

scholarly journals easyfm: An easy software suite for file manipulation of Next Generation Sequencing data on desktops

2021 ◽  
Author(s):  
Hyungtaek Jung ◽  
Brendan Jeon ◽  
Daniel Ortiz-Barrientos
Keyword(s):  
Next Generation Sequencing ◽  
Life Sciences ◽  
Next Generation Sequencing Data ◽  
Command Line ◽  
Next Generation ◽  
Web Based ◽  
File Formats ◽  
Wide Range ◽  
Ngs Data ◽  
Generation Sequencing

Storing and manipulating Next Generation Sequencing (NGS) file formats for understanding biological phenomena is an essential but difficult task in the life sciences. Yet, most methods for analysing NGS data require complex command-line tools in high-performance computing (HPC) or web-based servers and have not yet been implemented in comprehensive, easy-to-use software. Here we present easyfm (easy file manipulation), a free standalone Graphical User Interface (GUI) software with Python support that can be used to facilitate the rapid discovery of target sequences (or user’s interest) in NGS datasets for novice users (more accessible to biologists). It enables them to perform end-to-end reproducible data analyses using a desktop application (Windows, Mac and Linux). Unlike existing tools, the GUI-based easyfm is not dependent on any HPC system and can be operated without an internet connection. For user-friendliness and convenience, easyfm was developed with four work modules and a secondary GUI window, covering different aspects of NGS data analysis, including post-processing, filtering, format conversion, generating results, real-time log, and help. In combination with the executable tools (BLAST+ and BLAT) and Python, easyfm allows the user to set analysis parameters, select/extract regions of interest, examine the input and output results, and convert to a wide range of file formats. To help augment the functionality of existing web-based and command-line tools, easyfm, a self-contained program, comes with extensive documentation (https://github.com/TaekAndBrendan/easyfm). This specific benefit allows easyfm to seamlessly integrate visual and interactive representations of NGS files, supporting a wider scope of bioinformatics applications in the life sciences.

scholarly journals Comparative Metagenomic Analysis of Human Gut Microbiome Composition Using Two Different Bioinformatic Pipelines

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Valeria D’Argenio ◽  
Giorgio Casaburi ◽  
Vincenza Precone ◽  
Francesco Salvatore
Keyword(s):  
Microbial Community Composition ◽  
Diversity Analysis ◽  
Human Gut ◽  
Taxonomic Assignment ◽  
Microbiome Composition ◽  
Technological Advances ◽  
Wide Range ◽  
Family Level ◽  
Target Environment ◽  
Generation Sequencing

Technological advances in next-generation sequencing-based approaches have greatly impacted the analysis of microbial community composition. In particular, 16S rRNA-based methods have been widely used to analyze the whole set of bacteria present in a target environment. As a consequence, several specific bioinformatic pipelines have been developed to manage these data. MetaGenome Rapid Annotation using Subsystem Technology (MG-RAST) and Quantitative Insights Into Microbial Ecology (QIIME) are two freely available tools for metagenomic analyses that have been used in a wide range of studies. Here, we report the comparative analysis of the same dataset with both QIIME and MG-RAST in order to evaluate their accuracy in taxonomic assignment and in diversity analysis. We found that taxonomic assignment was more accurate with QIIME which, at family level, assigned a significantly higher number of reads. Thus, QIIME generated a more accurate BIOM file, which in turn improved the diversity analysis output. Finally, although informatics skills are needed to install QIIME, it offers a wide range of metrics that are useful for downstream applications and, not less important, it is not dependent on server times.

scholarly journals Re-Evaluation of the Podosphaera tridactyla Species Complex in Australia

2021 ◽  
Vol 7 (3) ◽  
pp. 171
Author(s):  
Reannon L. Smith ◽  
Tom W. May ◽  
Jatinder Kaur ◽  
Tim I. Sawbridge ◽  
Ross C. Mann ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Powdery Mildew ◽  
Species Complex ◽  
Taxonomic Revision ◽  
Stone Fruit ◽  
Prunus Species ◽  
Wide Range ◽  
Unidentified Species ◽  
The Rose ◽  
Generation Sequencing

The Podosphaera tridactyla species complex is highly variable morphologically and causes powdery mildew on a wide range of Prunus species, including stone fruit. A taxonomic revision of the Po. tridactyla species complex in 2020 identified 12 species, seven of which were newly characterised. In order to clarify which species of this complex are present in Australia, next generation sequencing was used to isolate the fungal ITS+28S and host matK chloroplast gene regions from 56 powdery mildew specimens of stone fruit and ornamental Prunus species accessioned as Po. tridactyla or Oidium sp. in Australian reference collections. The specimens were collected in Australia, Switzerland, Italy and Korea and were collected from 1953 to 2018. Host species were confirmed using matK phylogenetic analysis, which identified that four had been misidentified as Prunus but were actually Malusprunifolia. Podosphaera species were identified using ITS+28S phylogenetic analysis, recognising three Podosphaera species on stone fruit and related ornamental Prunus hosts in Australia. These were Po.pannosa, the rose powdery mildew, and two species in the Po. tridactyla species complex: Po. ampla, which was the predominant species, and a previously unidentified species from peach, which we describe here as Po. cunningtonii.

scholarly journals One4Two®: An Integrated Molecular Approach to Optimize Infertile Couples’ Journey

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 60
Author(s):  
Valeria D’Argenio ◽  
Federica Cariati ◽  
Rossella Tomaiuolo
Keyword(s):  
Disease Genes ◽  
Diagnostic Efficacy ◽  
Whole Process ◽  
Pathogenic Variants ◽  
Limiting Step ◽  
Number Of Genes ◽  
Infertile Couples ◽  
Next Generation Sequencing Ngs ◽  
And Diffusion ◽  
Generation Sequencing

The current diagnostic path of infertile couples is long lasting and often ineffective. Genetic tests, in particular, appear as a limiting step due to their jeopardized use on one side, and to the limited number of genes evaluated on the other. In this context, the development and diffusion, also in routine diagnostic settings, of next generation sequencing (NGS)-based methods for the analyses of several genes in multiple subjects at a time is improving the diagnostic sensitivity of molecular analyses. Thus, we developed One4Two®, a custom NGS panel to optimize the diagnostic journey of infertile couples. The panel validation was carried out in three steps analyzing a total of 83 subjects. Interestingly, all the previously identified variants were confirmed, assessing the analytic sensitivity of the method. Moreover, additional pathogenic variants have been identified underlying the diagnostic efficacy of the proposed method. One4Two® allows the simultaneous analysis of infertility-related genes, disease-genes of common inherited diseases, and of polymorphisms related to therapy outcome. Thus, One4Two® is able to improve the diagnostic journey of infertile couples by simplifying the whole process not only for patients, but also for laboratories and reproduction specialists moving toward an even more personalized medicine.

scholarly journals Exploring the physical controls of regional patterns of flow duration curves – Part 4: A synthesis of empirical analysis, process modeling and catchment classification

2012 ◽  
Vol 16 (11) ◽  
pp. 4483-4498 ◽  
Author(s):  
M. Yaeger ◽  
E. Coopersmith ◽  
S. Ye ◽  
L. Cheng ◽  
A. Viglione ◽  
...  
Keyword(s):  
Low Flow ◽  
Middle Portion ◽  
Qualitative Synthesis ◽  
Statistical Parameters ◽  
Regional Patterns ◽  
Flow Duration ◽  
Analysis Process ◽  
Wide Range ◽  
Physical Controls ◽  
Flow Duration Curves

Abstract. The paper reports on a four-pronged study of the physical controls on regional patterns of the flow duration curve (FDC). This involved a comparative analysis of long-term continuous data from nearly 200 catchments around the US, encompassing a wide range of climates, geology, and ecology. The analysis was done from three different perspectives – statistical analysis, process-based modeling, and data-based classification – followed by a synthesis, which is the focus of this paper. Streamflow data were separated into fast and slow flow responses, and associated signatures, and both total flow and its components were analyzed to generate patterns. Regional patterns emerged in all aspects of the study. The mixed gamma distribution described well the shape of the FDC; regression analysis indicated that certain climate and catchment properties were first-order controls on the shape of the FDC. In order to understand the spatial patterns revealed by the statistical study, and guided by the hypothesis that the middle portion of the FDC is a function of the regime curve (RC, mean within-year variation of flow), we set out to classify these catchments, both empirically and through process-based modeling, in terms of their regime behavior. The classification analysis showed that climate seasonality and aridity, either directly (empirical classes) or through phenology (vegetation processes), were the dominant controls on the RC. Quantitative synthesis of these results determined that these classes were indeed related to the FDC through its slope and related statistical parameters. Qualitative synthesis revealed much diversity in the shapes of the FDCs even within each climate-based homogeneous class, especially in the low-flow tails, suggesting that catchment properties may have become the dominant controls. Thus, while the middle portion of the FDC contains the average response of the catchment, and is mainly controlled by climate, the tails of the FDC, notably the low-flow tails, are mainly controlled by catchment properties such as geology and soils. The regime behavior explains only part of the FDC; to gain a deeper understanding of the physical controls on the FDC, these extremes must be analyzed as well. Thus, to completely separate the climate controls from the catchment controls, the roles of catchment properties such as soils, geology, topography etc. must be explored in detail.

THE SURGICAL MANAGEMENT OF PEDIATRIC HYDROCEPHALUS

Neurosurgery ◽  
2008 ◽  
Vol 62 (suppl_2) ◽  
pp. SHC633-SHC642 ◽  
Author(s):  
James M. Drake
Keyword(s):  
Surgical Management ◽  
Computer Models ◽  
Future Directions ◽  
Complex Disorders ◽  
Computed Tomographic ◽  
Pediatric Hydrocephalus ◽  
Past Generation ◽  
Current State ◽  
Technological Advances ◽  
Hydrocephalus Treatment

Abstract THE SURGICAL MANAGEMENT of hydrocephalus has undergone incredible changes over the past generation of neurosurgeons, including dramatic improvements in imaging, especially computed tomographic scanning and magnetic resonance imaging, and remarkably innovative advances in cerebrospinal fluid valve technology, complex computer models, and endoscopic equipment and techniques. In terms of overall patient outcomes, however, one could conclude that things are a little better, but “not much.” This frustrating yet fascinating dichotomy between technological advancements and clinical outcomes makes hydrocephalus, first described by the ancients, as one of the most understated and complex disorders that neurosurgeons treat. The challenge to the next generation of neurosurgeons is to solve this vexing problem through better understanding of the basic science, improved computer models, additional technological advances, and, most importantly, a broad-based, concerted multidisciplinary attack on this disorder. This review focuses on the evolution of surgery for hydrocephalus over the last 30 years, the current state of the art of hydrocephalus treatment, and what appear to be the most promising future directions.

scholarly journals What is Normalization? The Strategies Employed in Top-Down and Bottom-Up Proteome Analysis Workflows

Proteomes ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 29 ◽  
Author(s):  
Matthew B. O’Rourke ◽  
Stephanie E. L. Town ◽  
Penelope V. Dalla ◽  
Fiona Bicknell ◽  
Naomi Koh Belic ◽  
...  
Keyword(s):  
Normal State ◽  
Proteome Analysis ◽  
Biological Condition ◽  
Sample Handling ◽  
Analysis Process ◽  
Starting Point ◽  
Wide Range ◽  
Experimental Process ◽  
Definition Of ◽  
Accurate Quantification

The accurate quantification of changes in the abundance of proteins is one of the main applications of proteomics. The maintenance of accuracy can be affected by bias and error that can occur at many points in the experimental process, and normalization strategies are crucial to attempt to overcome this bias and return the sample to its regular biological condition, or normal state. Much work has been published on performing normalization on data post-acquisition with many algorithms and statistical processes available. However, there are many other sources of bias that can occur during experimental design and sample handling that are currently unaddressed. This article aims to cast light on the potential sources of bias and where normalization could be applied to return the sample to its normal state. Throughout we suggest solutions where possible but, in some cases, solutions are not available. Thus, we see this article as a starting point for discussion of the definition of and the issues surrounding the concept of normalization as it applies to the proteomic analysis of biological samples. Specifically, we discuss a wide range of different normalization techniques that can occur at each stage of the sample preparation and analysis process.

scholarly journals Whole exome sequencing in 17 consanguineous Iranian pedigrees expands the mutational spectrum of inherited retinal dystrophies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atta Ur Rehman ◽  
Neda Sepahi ◽  
Nicola Bedoni ◽  
Zeinab Ravesh ◽  
Arash Salmaninejad ◽  
...  
Keyword(s):  
Disease Genes ◽  
Homozygous State ◽  
Traditional Practice ◽  
Genomic Variants ◽  
Mutational Spectrum ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Whole Exome ◽  
Human Disorders ◽  
Generation Sequencing

AbstractInherited retinal dystrophies (IRDs) constitute one of the most heterogeneous groups of Mendelian human disorders. Using autozygome-guided next-generation sequencing methods in 17 consanguineous pedigrees of Iranian descent with isolated or syndromic IRD, we identified 17 distinct genomic variants in 11 previously-reported disease genes. Consistent with a recessive inheritance pattern, as suggested by pedigrees, variants discovered in our study were exclusively bi-allelic and mostly in a homozygous state (in 15 families out of 17, or 88%). Out of the 17 variants identified, 5 (29%) were never reported before. Interestingly, two mutations (GUCY2D:c.564dup, p.Ala189ArgfsTer130 and TULP1:c.1199G > A, p.Arg400Gln) were also identified in four separate pedigrees (two pedigrees each). In addition to expanding the mutational spectrum of IRDs, our findings confirm that the traditional practice of endogamy in the Iranian population is a prime cause for the appearance of IRDs.

scholarly journals Integration of image segmentation and fuzzy theory to improve the accuracy of damage detection areas in traffic accidents

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Majid Amirfakhrian ◽  
Mahboub Parhizkar
Keyword(s):  
Machine Learning ◽  
Image Processing ◽  
Machine Vision ◽  
Traffic Accidents ◽  
Fuzzy Theory ◽  
Machine Learning Techniques ◽  
Industrial Setting ◽  
Technological Advances ◽  
Learning Techniques ◽  
Wide Range

AbstractIn the next decade, machine vision technology will have an enormous impact on industrial works because of the latest technological advances in this field. These advances are so significant that the use of this technology is now essential. Machine vision is the process of using a wide range of technologies and methods in providing automated inspections in an industrial setting based on imaging, process control, and robot guidance. One of the applications of machine vision is to diagnose traffic accidents. Moreover, car vision is utilized for detecting the amount of damage to vehicles during traffic accidents. In this article, using image processing and machine learning techniques, a new method is presented to improve the accuracy of detecting damaged areas in traffic accidents. Evaluating the proposed method and comparing it with previous works showed that the proposed method is more accurate in identifying damaged areas and it has a shorter execution time.

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