scholarly journals Probabilistic recovery of cryptic haplotypes from metagenomic data

2017 ◽  
Author(s):  
Samuel M. Nicholls ◽  
Wayne Aubrey ◽  
Kurt de Grave ◽  
Leander Schietgat ◽  
Christopher J. Creevey ◽  
...  
Keyword(s):  
Microbial Communities ◽  
A Priori ◽  
Probabilistic Approach ◽  
Region Of Interest ◽  
Difficult Problem ◽  
Genomic Region ◽  
Metagenomic Data ◽  
Alignment Error ◽  
Hiv 1

AbstractThe cryptic diversity of microbial communities represent an untapped biotechnological resource for biomining, biorefining and synthetic biology. Revealing this information requires the recovery of the exact sequence of DNA bases (or “haplotype”) that constitutes the genes and genomes of every individual present. This is a computationally difficult problem complicated by the requirement for environmental sequencing approaches (metagenomics) due to the resistance of the constituent organisms to culturing in vitro.Haplotypes are identified by their unique combination of DNA variants. However, standard approaches for working with metagenomic data require simplifications that violate assumptions in the process of identifying such variation. Furthermore, current haplotyping methods lack objective mechanisms for choosing between alternative haplotype reconstructions from microbial communities.To address this, we have developed a novel probabilistic approach for reconstructing haplotypes from complex microbial communities and propose the “metahaplome” as a definition for the set of haplotypes for any particular genomic region of interest within a metagenomic dataset. Implemented in the twin software tools Hansel and Gretel, the algorithm performs incremental probabilistic haplotype recovery using Naive Bayes — an efficient and effective technique.Our approach is capable of reconstructing the haplotypes with the highest likelihoods from metagenomic datasets without a priori knowledge or making assumptions of the distribution or number of variants. Additionally, the algorithm is robust to sequencing and alignment error without altering or discarding observed variation and uses all available evidence from aligned reads. We validate our approach using synthetic metahaplomes constructed from sets of real genes, and demonstrate its capability using metagenomic data from a complex HIV-1 strain mix. The results show that the likelihood framework can allow recovery from microbial communities of cryptic functional isoforms of genes with 100% accuracy.

scholarly journals Advances in the recovery of haplotypes from the metagenome

2016 ◽  
Author(s):  
Samuel M. Nicholls ◽  
Wayne Aubrey ◽  
Kurt de Grave ◽  
Leander Schietgat ◽  
Christopher J. Creevey ◽  
...  
Keyword(s):  
Sequence Variation ◽  
A Priori ◽  
Region Of Interest ◽  
Genomic Region ◽  
Metagenomic Data ◽  
Proof Of Concept ◽  
Data Set ◽  
Single Organism ◽  
High Throughput Dna Sequencing ◽  
Concept Framework

AbstractHigh-throughput DNA sequencing has enabled us to look beyond consensus reference sequences to the variation observed in sequences within organisms; their haplotypes. Recovery, or assembly of haplotypes has proved computationally difficult and there exist many probabilistic heuristics that attempt to recover the original haplotypes for a single organism of known ploidy. However, existing approaches make simplifications or assumptions that are easily violated when investigating sequence variation within a metagenome.We propose the metahaplome as the set of haplotypes for any particular genomic region of interest within a metagenomic data set and present Hansel and Gretel, a data structure and algorithm that together provide a proof of concept framework for the recovery of true haplotypes from a metagenomic data set. The algorithm performs incremental haplotype recovery, using smoothed Naive Bayes — a simple, efficient and effective method.Hansel and Gretel pose several advantages over existing solutions: the framework is capable of recovering haplotypes from metagenomes, does not require a priori knowledge about the input data, makes no assumptions regarding the distribution of alleles at variant sites, is robust to error, and uses all available evidence from aligned reads, without altering or discarding observed variation. We evaluate our approach using synthetic metahaplomes constructed from sets of real genes and show that up to 99% of SNPs on a haplotype can be correctly recovered from short reads that originate from a metagenomic data set.

DEVELOPMENT OF APPROACHES FOR DETECTION OF GENOME-INTEGRATED PROVIRAL DNA OF THE HUMAN IMMUNODEFICIENCY VIRUS (HIV-1) IN ULTRA LOW CONCENTRATIONS USING THE CRISPR/CAS SYSTEM

2020 ◽  
Author(s):  
M.A. Tyumentseva ◽  
◽  
A.I. Tyumentsev ◽  
V.G. Akimkin ◽  
◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Health Monitoring ◽  
Biological Samples ◽  
Proviral Dna ◽  
Guide Rnas ◽  
Ribonucleoprotein Complexes ◽  
Low Concentrations ◽  
Immunodeficiency Virus ◽  
Hiv 1

For the effective functioning of supervisory and health monitoring services, it is necessary to introduce modern molecular technologies into their practice. Therefore, the task of developing new effective methods for detecting pathogen, for example HIV, based on CRISPR/CAS genome editing systems, remains urgent. In the present work, guide RNAs and specific oligonucleotides were developed for preliminary amplification of highly conserved regions of the HIV-1 genome. The developed guide RNAs make it possible to detect single copies of HIV-1 proviral DNA in vitro as part of CRISPR/CAS ribonucleoprotein complexes in biological samples after preliminary amplification.

In vitro binding activity between HCK SH3 domain and HIV-1 Nef protein

2011 ◽  
Vol 31 (3) ◽  
pp. 262-265
Author(s):  
Xiao-lin QIN ◽  
Chao-qi LIU ◽  
Dong-ming REN ◽  
Yong-qin ZHOU
Keyword(s):  
Sh3 Domain ◽  
Binding Activity ◽  
Hiv 1

Anti HIV-1 Agents 7. Discovery of 1-Hydroxy-4-chloro-9,10-anthraquinone Derivatives as New HIV-1 Inhibitors in Vitro

2011 ◽  
Vol 8 (7) ◽  
pp. 602-605
Author(s):  
Ning Huang ◽  
Qin Wang ◽  
Liu-Meng Yang ◽  
Hui Xu ◽  
Yong-Tang Zheng
Keyword(s):  
Anthraquinone Derivatives ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals 1592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity.

1997 ◽  
Vol 41 (5) ◽  
pp. 1082-1093 ◽  
Author(s):  
S M Daluge ◽  
S S Good ◽  
M B Faletto ◽  
W H Miller ◽  
M H St Clair ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Oral Bioavailability ◽  
Human Peripheral Blood ◽  
Cross Resistance ◽  
Immunodeficiency Virus ◽  
Carbocyclic Nucleoside ◽  
Hiv 1 ◽  
In Cells

1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclo pentene-1-methanol, is a carbocyclic nucleoside with a unique biological profile giving potent, selective anti-human immunodeficiency virus (HIV) activity. 1592U89 was selected after evaluation of a wide variety of analogs containing a cyclopentene substitution for the 2'-deoxyriboside of natural deoxynucleosides, optimizing in vitro anti-HIV potency, oral bioavailability, and central nervous system (CNS) penetration. 1592U89 was equivalent in potency to 3'-azido-3'-deoxythymidine (AZT) in human peripheral blood lymphocyte (PBL) cultures against clinical isolates of HIV type 1 (HIV-1) from antiretroviral drug-naive patients (average 50% inhibitory concentration [IC50], 0.26 microM for 1592U89 and 0.23 microM for AZT). 1592U89 showed minimal cross-resistance (approximately twofold) with AZT and other approved HIV reverse transcriptase (RT) inhibitors. 1592U89 was synergistic in combination with AZT, the nonnucleoside RT inhibitor nevirapine, and the protease inhibitor 141W94 in MT4 cells against HIV-1 (IIIB). 1592U89 was anabolized intracellularly to its 5'-monophosphate in CD4+ CEM cells and in PBLs, but the di- and triphosphates of 1592U89 were not detected. The only triphosphate found in cells incubated with 1592U89 was that of the guanine analog (-)-carbovir (CBV). However, the in vivo pharmacokinetic, distribution, and toxicological profiles of 1592U89 were distinct from and improved over those of CBV, probably because CBV itself was not appreciably formed from 1592U89 in cells or animals (<2%). The 5'-triphosphate of CBV was a potent, selective inhibitor of HIV-1 RT, with Ki values for DNA polymerases (alpha, beta, gamma, and epsilon which were 90-, 2,900-, 1,200-, and 1,900-fold greater, respectively, than for RT (Ki, 21 nM). 1592U89 was relatively nontoxic to human bone marrow progenitors erythroid burst-forming unit and granulocyte-macrophage CFU (IC50s, 110 microM) and human leukemic and liver tumor cell lines. 1592U89 had excellent oral bioavailability (105% in the rat) and penetrated the CNS (rat brain and monkey cerebrospinal fluid) as well as AZT. Having demonstrated an excellent preclinical profile, 1592U89 has progressed to clinical evaluation in HIV-infected patients.

In vitro synthesis of enzymatically active HIV-1 protease for rapid phenotypic resistance profiling

2005 ◽  
Vol 32 (4) ◽  
pp. 294-299 ◽  
Author(s):  
Dieter Hoffmann ◽  
Bernd Buchberger ◽  
Cordula Nemetz
Keyword(s):  
In Vitro Synthesis ◽  
Phenotypic Resistance ◽  
Hiv 1

scholarly journals In silico design and in vitro expression of novel multiepitope DNA constructs based on HIV-1 proteins and Hsp70 T-cell epitopes

2021 ◽  
Author(s):  
Elahe Akbari ◽  
Kimia Kardani ◽  
Ali Namvar ◽  
Soheila Ajdary ◽  
Esmat Mirabzadeh Ardakani ◽  
...  
Keyword(s):  
T Cell ◽  
In Silico ◽  
T Cell Epitopes ◽  
In Vitro Expression ◽  
In Silico Design ◽  
Hiv 1
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