scholarly journals BlastFrost: Fast querying of 100,000s of bacterial genomes in Bifrost graphs

2020 ◽  
Author(s):  
Nina Luhmann ◽  
Guillaume Holley ◽  
Mark Achtman
Keyword(s):  
Data Structure ◽  
Fluoroquinolone Resistance ◽  
Nucleotide Polymorphisms ◽  
Bacterial Genomes ◽  
Single Nucleotide ◽  
De Bruijn Graphs ◽  
Practical Applications ◽  
The Individual ◽  
Dynamic Data Structure ◽  
Genome Assemblies

AbstractBlastFrost is a highly efficient method for querying 100,000s of genome assemblies. It builds on Bifrost, a recently developed dynamic data structure for compacted and colored de Bruijn graphs from bacterial genomes. BlastFrost queries a Bifrost data structure for sequences of interest, and extracts local subgraphs, thereby enabling the efficient identification of the presence or absence of individual genes or single nucleotide sequence variants. Here we describe the algorithms and implementation of BlastFrost. We also present two exemplar practical applications. In the first, we determined the presence of the individual genes within the SPI-2 Salmonella pathogenicity island within a collection of 926 representative genomes in minutes. In the second application, we determined the existence of known single nucleotide polymorphisms associated with fluoroquinolone resistance in the genes gyrA, gyrB and parE among 190, 209 Salmonella genomes. BlastFrost is available for download at https://github.com/nluhmann/BlastFrost.

scholarly journals From raw reads to trees: Whole genome SNP phylogenetics across the tree of life

2015 ◽  
Author(s):  
Sanaa Afroz Ahmed ◽  
Chien-Chi Lo ◽  
Po-E Li ◽  
Karen W Davenport ◽  
Patrick S.G. Chain
Keyword(s):  
Ad Hoc ◽  
Phylogenetic Reconstruction ◽  
Clinical Samples ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Complex Samples ◽  
Phylogenetic Characterization ◽  
Genome Wide ◽  
Genome Assemblies

Next-generation sequencing is increasingly being used to examine closely related organisms. However, while genome-wide single nucleotide polymorphisms (SNPs) provide an excellent resource for phylogenetic reconstruction, to date evolutionary analyses have been performed using different ad hoc methods that are not often widely applicable across different projects. To facilitate the construction of robust phylogenies, we have developed a method for genome-wide identification/characterization of SNPs from sequencing reads and genome assemblies. Our phylogenetic and molecular evolutionary (PhaME) analysis software is unique in its ability to take reads and draft/complete genome(s) as input, derive core genome alignments, identify SNPs, construct phylogenies and perform evolutionary analyses. Several examples using genomes and read datasets for bacterial, eukaryotic and viral linages demonstrate the broad and robust functionality of PhaME. Furthermore, the ability to incorporate raw metagenomic reads from clinical samples with suspected infectious agents shows promise for the rapid phylogenetic characterization of pathogens within complex samples.

scholarly journals Metannot: A succinct data structure for compression of colors in dynamic de Bruijn graphs

2017 ◽  
Author(s):  
Harun Mustafa ◽  
André Kahles ◽  
Mikhail Karasikov ◽  
Gunnar Rätsch
Keyword(s):  
Data Structure ◽  
High Throughput Sequencing ◽  
Sequence Data ◽  
Data Sets ◽  
Sequencing Data ◽  
Dynamic Data ◽  
De Bruijn Graphs ◽  
Dna And Rna ◽  
Succinct Data Structure ◽  
Dynamic Data Structure

AbstractMuch of the DNA and RNA sequencing data available is in the form of high-throughput sequencing (HTS) reads and is currently unindexed by established sequence search databases. Recent succinct data structures for indexing both reference sequences and HTS data, along with associated metadata, have been based on either hashing or graph models, but many of these structures are static in nature, and thus, not well-suited as backends for dynamic databases.We propose a parallel construction method for and novel application of the wavelet trie as a dynamic data structure for compressing and indexing graph metadata. By developing an algorithm for merging wavelet tries, we are able to construct large tries in parallel by merging smaller tries constructed concurrently from batches of data.When compared against general compression algorithms and those developed specifically for graph colors (VARI and Rainbowfish), our method achieves compression ratios superior to gzip and VARI, converging to compression ratios of 6.5% to 2% on data sets constructed from over 600 virus genomes.While marginally worse than compression by bzip2 or Rainbowfish, this structure allows for both fast extension and query. We also found that additionally encoding graph topology metadata improved compression ratios, particularly on data sets consisting of several mutually-exclusive reference genomes.It was also observed that the compression ratio of wavelet tries grew sublinearly with the density of the annotation matrices.This work is a significant step towards implementing a dynamic data structure for indexing large annotated sequence data sets that supports fast query and update operations. At the time of writing, no established standard tool has filled this niche.

scholarly journals The role of genetic polymorphism in the formation of atherosclerosis in the vessels of lower extremities

2012 ◽  
Vol 93 (3) ◽  
pp. 513-516
Author(s):  
M N Katina ◽  
R F Gayfullina ◽  
V V Valiullin ◽  
A A Rizvanov ◽  
R F Khamitov ◽  
...  
Keyword(s):  
Human Genome ◽  
Literature Search ◽  
Lower Extremities ◽  
Disease Course ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Human Genes ◽  
Genomics And Proteomics ◽  
The Individual

Personalized medicine involves the use of methods of genomics and proteomics by physicians for early diagnosis, prediction of the nature of the disease course and the choice of medicines and their doses based on personalized characteristics of the individual patient. Advances in the study of the human genome make it possible to reveal the interrelation between the individual mutations in the human genes (polymorphisms) and predisposition to certain diseases. Currently there are more than 10 million single-nucleotide polymorphisms in the human genome, however their biological role remains poorly understood. On the basis of a literature search of electronic full-text and abstract-only versions of articles, which was conducted in the PUBMED, OMIM and GENE databases, collected was the information on genetic predisposition to systemic atherosclerosis. The review is dedicated to polymorphisms of the major genes that play a role in the pathophysiology of atherosclerosis of the lower extremities.

ABCB1, CYP3A5*3, and CYP3A4*1B SNPs and risk of toxicity with sunitinib treatment for mRCC.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 485-485
Author(s):  
Maria Bassanelli ◽  
Alessandra Felici ◽  
Michele Milella ◽  
Diana Giannarelli ◽  
Silvana Giacinti ◽  
...  
Keyword(s):  
Nucleotide Polymorphisms ◽  
Test Results ◽  
Chi Square ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Genes Encoding ◽  
Hand Foot Syndrome ◽  
Chi Square Test ◽  
Grade 3 ◽  
The Individual

485 Background: Currently there are no biomarkers to predict either toxicity or activity of targeted therapy in mRCC. The aim of this study was to correlate single nucleotide polymorphisms (SNPs) of genes encoding for efflux transporters and metabolizing enzymes with sunitinib toxicity in metastatic renal cell carcinoma (mRCC) patients (pts). Methods: We conducted an observational, retrospective analysis of 60 Caucasian pts who received sunitinib for mRCC from 2 Italian institutions. Correlation between adverse events (AE, according to CTCAE v.4.0) and 4 polymorphisms in 3 genes (ABCB1 [1236C>T, 3435C>T], CYP3A5*3 6986A>G, CYP3A4*1B-392A>G) was analyzed. SNPs were detected in blood samples using pyrosequencing technique. Association between SNPs and toxicities was evaluated using the Chi Square test. Results: 60pts (median age: 61 years; male: 63.3%) with mRCC (clear cell: 85%, other histologies: 15%) were treated with sunitinib (83.3% as first-line). The most common AE (any-grade) reported were: hypertension (85%), asthenia (83.3%), hypothyroidism (65%), anemia (61.6%), nausea/vomiting (60%), stomatitis (58.3%), diarrhoea (48.3%), neutropenia (48.3%), thrombocytopenia (46.7%), leukopenia (46.7%), hypertriglyceridemia (45%), hyperglycaemia (38.4%), hypercholesterolemia (35%), and hand-foot syndrome (35%). Treatment was discontinued and sunitinib dose was reduced due to AE in 28.3% and 61.7% of pts, respectively. The G/A-variant in CYP3A5*3 was associated with thrombocytopenia (any grade, p=0.03); homozygous C/C alleles in ABCB1 1236C>T significantly correlated with leukopenia (any grade, p=0.01), while the C/C genotype in ABCB1 3435C>T was associated with hypertension (grade≥3, p=0.05); hypertriglyceridemia showed a trend towards increased prevalence in the presence of the C allele (grade≥3, p=0.08). Conclusions: Polymorphisms in ABCB1 and CYP3A5*3 are predictive of toxicity, as hypertension, leukopenia, and thrombocytopenia in pts with mRCC treated with sunitinib. This analysis could support the selection of the more appropriate drug to the individual patient.

Single Nucleotide Polymorphisms (SNPs): History, Biotechnological Outlook and Practical Applications

2005 ◽  
Vol 3 (3) ◽  
pp. 237-245 ◽  
Author(s):  
Shelina Kassam ◽  
Peter Meyer ◽  
Anthony Corfield ◽  
Gregor Mikuz ◽  
Consolato Sergi
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Practical Applications

A practical parameterised algorithm for the individual haplotyping problem MLF

2010 ◽  
Vol 20 (5) ◽  
pp. 851-863 ◽  
Author(s):  
MINZHU XIE ◽  
JIANXIN WANG ◽  
JIANER CHEN
Keyword(s):  
Dna Sequence ◽  
Complex Disease ◽  
Disease Gene ◽  
Exact Algorithm ◽  
Biological Applications ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Disease Gene Mapping ◽  
A Genome ◽  
The Individual

Haplotypes are more useful in complex disease gene mapping than single-nucleotide polymorphisms (SNPs). However, haplotypes are difficult to obtain directly using biological experiments, which has prompted research into efficient computational methods for determining haplotypes. The individual haplotyping problem called Minimum Letter Flip (MLF) is a computational problem that, given a set of aligned DNA sequence fragment data of an individual, induces the corresponding haplotypes by flipping minimum SNPs. There has been no practical exact algorithm for solving the problem. Due to technical limits in DNA sequencing experiments, the maximum length of a fragment sequenced directly is about 1kb. In consequence, with a genome-average SNP density of 1.84 SNPs per 1 kb of DNA sequence, the maximum number k1 of SNP sites that a fragment covers is usually small. Moreover, in order to save time and money, the maximum number k2 of fragments that cover an SNP site is usually no more than 19. Building on these fragment data properties, the current paper introduces a new parameterised algorithm with running time O(nk22k2 + mlogm + mk1), where m is the number of fragments and n is the number of SNP sites. In practical biological applications, the algorithm solves the MLF problem efficiently even if m and n are large.

The Relationship of TLR2 Polymorphisms with Infectious Diseases

2021 ◽  
pp. 57-73
Author(s):  
Marcos Jessé Abrahão Silva ◽  
Marceli Batista Martins Lima ◽  
Karla Valéria Batista Lima ◽  
Luana Nepomuceno Gondim Costa Lima
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Cochrane Collaboration ◽  
Nucleotide Polymorphisms ◽  
Proinflammatory Response ◽  
Single Nucleotide ◽  
The Usa ◽  
The Individual ◽  
Relationship Of ◽  
The Relationship

The proinflammatory response induced by Toll-Like receptors (TLR) is considered the host's first defense line. Single nucleotide polymorphisms (SNPs) correspond to the most frequent type of variation in the human genome, and due to the importance of TLR2 in the immune response, SNPs in the TLR gene are related to susceptibility or resistance to various diseases. Thus, the objective of the present study was to identify the polymorphisms existing in the TLR2 gene that may cause susceptibility or protection against infectious diseases. We conducted a systematic review of the literature in the databases Science Direct, National Library of Medicine National Institutes of Health of the USA (PUBMED), Cochrane Collaboration and Medical Literature Analysis and Retrieval System Online (MEDLINE) between 2000 to 2020. The search resulted in 32 articles, all of which in English. Thus, it was demonstrated that the related polymorphisms are extremely important for the identification of related pathologies, whether for the susceptibility or protection of the individual to the diseases, also being essential for the mechanisms of signal generation and immune responses, and finally indicating that a balance between activation and inactivating these receptors to prevent an excessive inflammatory or immune response.

scholarly journals Nutrigenomics, individualism and public health

2004 ◽  
Vol 63 (1) ◽  
pp. 161-166 ◽  
Author(s):  
Ruth Chadwick
Keyword(s):  
Public Health ◽  
Genetic Variation ◽  
Functional Foods ◽  
Ethical Issues ◽  
Public Confidence ◽  
Nucleotide Polymorphisms ◽  
Dietary Recommendations ◽  
Single Nucleotide ◽  
The Individual ◽  
The Relationship

Issues arising in connection with genes and nutrition policy include both nutrigenomics and nutrigenetics. Nutrigenomics considers the relationship between specifc nutrients or diet and gene expression and, it is envisaged, will facilitate prevention of diet-related common diseases. Nutrigenetics is concerned with the effects of individual genetic variation (single nucleotide polymorphisms) on response to diet, and in the longer term may lead to personalised dietary recommendations. It is important also to consider the surrounding context of other issues such as novel and functional foods in so far as they are related to genetic modification. Ethical issues fall into a number of categories: (1) why nutrigenomics? Will it have important public health benefits? (2) questions about research, e.g. concerning the acquisition of information about individual genetic variation; (3) questions about who has access to this information, and its possible misuse; (4) the applications of this information in terms of public health policy, and the negotiation of the potential tension between the interests of the individual in relation to, for example, prevention of conditions such as obesity and allergy; (5) the appropriate ethical approach to the issues, e.g. the moral difference, if any, between therapy and enhancement in relation to individualised diets; whether the 'technological fix' is always appropriate, especially in the wider context of the purported lack of public confidence in science, which has special resonance in the sphere of nutrition.

Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation

Blood ◽  
2006 ◽  
Vol 107 (1) ◽  
pp. 118-125 ◽  
Author(s):  
Barbara Plaimauer ◽  
Jakob Fuhrmann ◽  
Gabriele Mohr ◽  
Waltraud Wernhart ◽  
Katharina Bruno ◽  
...  
Keyword(s):  
Amino Acid ◽  
Missense Mutation ◽  
Specific Activity ◽  
Phenotypic Expression ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Common Amino Acid ◽  
Sequence Variations ◽  
Adamts13 Deficiency ◽  
The Individual

Abstract Sequence analysis of the ADAMTS13 locus of 2 patients with hereditary thrombotic thrombocytopenic purpura (TTP) revealed the homozygous presence of 4 single nucleotide polymorphisms (SNPs) (R7W, Q448E, P618A, A732V) and a rare missense mutation (R1336W). Analysis of the individual effect of any amino acid exchanges showed that several sequence variations can interact with each other, thereby altering the phenotype of ADAMTS13 deficiency. Introduction of polymorphisms R7W, Q448E, and A732V had no or only minor effects on ADAMTS13 secretion. In contrast, P618A, R1336W, and the A732V-P618A combination strongly reduced ADAMTS13-specific activity and antigen levels. Surprisingly, R7W and Q448E were positive modifiers of ADAMTS13 secretion in the context of P618A and A732V but neither could rescue the severely reduced specific activity conferred by P618A. However, in the context of R1336W, polymorphisms R7W and Q448E enhanced the detrimental effect of the missense mutation and led to undetectable enzyme activity. We show that dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression. Our results might therefore be widely relevant to understanding the influence of polymorphisms on the phenotypic expression of complex diseases.

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