scholarly journals Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bénedith Oben ◽  
Guy Froyen ◽  
Kylee H. Maclachlan ◽  
Daniel Leongamornlert ◽  
Federico Abascal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Monoclonal Gammopathy ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Driver Genes ◽  
Smoldering Myeloma ◽  
Undetermined Significance

AbstractMultiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n = 15) are characterized by later initiation in the patient’s life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. This data provides evidence that WGS can be used to recognize two biologically and clinically distinct myeloma precursor entities that are either progressive or stable.

scholarly journals Whole genome sequencing provides evidence of two biologically and clinically distinct entities of asymptomatic monoclonal gammopathies: progressive versus stable myeloma precursor condition

2020 ◽  
Author(s):  
Bénedith Oben ◽  
Guy Froyen ◽  
Kylee H. Maclachlan ◽  
Daniel Leongamornlert ◽  
Federico Abascal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Monoclonal Gammopathy ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Driver Genes ◽  
Smoldering Myeloma ◽  
First Time ◽  
Undetermined Significance

AbstractMultiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate, for the first time, the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n=15) are characterized by later initiation in the patient’s life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. This data provides evidence that WGS can be used to recognize two biologically and clinically distinct myeloma precursor entities that are either progressive or stable.

scholarly journals Five-year Microevolution of a Multidrug-Resistant Mycobacterium Tuberculosis Strain within a Patient with Inadequate Compliance to Treatment.

2021 ◽  
Author(s):  
Dario Fernández Do Porto ◽  
Johana Monteserin ◽  
Josefina Campos ◽  
Ezequiel J Sosa ◽  
Mario Matteo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Treatment Compliance ◽  
Whole Genome Sequence ◽  
Intermittent Therapy ◽  
Whole Genome ◽  
Short Term ◽  
Depth Analysis

Abstract BackgroundWhole-genome sequencing has shown that the Mycobacterium tuberculosis infection process can be more heterogeneous than previously thought. Compartmentalized infections, exogenous reinfections, and microevolution are manifestations of this clonal complexity. The analysis of the mechanisms causing the microevolution —the genetic variability of M. tuberculosis at short time scales— of a parental strain into clonal variants with a patient is a relevant issue that has not been yet completely addressed. To our knowledge, a whole genome sequence microevolution analysis in a single patient with inadequate adherence to treatment has not been previously reported.Case Presentations In this work, we applied whole genome sequencing for a more in-depth analysis of the microevolution of a parental Mycobacterium tuberculosis strain into clonal variants within a patient with poor treatment compliance in Argentina. We analyzed the whole-genome sequence of 8 consecutive Mycobacterium. tuberculosis isolates obtained from a patient within 57-month of intermittent therapy. Nineteen mutations (9 short-term, 10 fixed variants) emerged, most of them associated with drug resistance. The first isolate was already resistant to isoniazid, rifampicin, and streptomycin, thereafter the strain developed resistance to fluoroquinolones and pyrazinamide. Surprisingly, isolates remained susceptible to the pro-drug ethionamide after acquiring a frameshift mutation in ethA, a gene required for its activation. We also found a novel variant, (T-54G), in the 5' untranslated region of whiB7 (T-54G), a region allegedly related to kanamycin resistance. Notably, discrepancies between canonical and phage-based susceptibility testing to kanamycin were previously found for the isolate harboring this mutation. In our patience, microevolution was mainly driven by drug selective pressure. Rare short-term mutations fixed together with resistance-conferring mutations during therapy.ConclusionsThis report highlights the relevance of whole-genome sequencing in the clinic for characterization of pre-XDR and MDR resistance profile, particularly in patients with incomplete and/or intermittent treatment.

scholarly journals Five-year microevolution of a multidrug-resistant Mycobacterium tuberculosis strain within a patient with inadequate compliance to treatment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Darío A. Fernandez Do Porto ◽  
Johana Monteserin ◽  
Josefina Campos ◽  
Ezequiel J. Sosa ◽  
Mario Matteo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Whole Genome Sequence ◽  
Intermittent Therapy ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Short Term ◽  
Depth Analysis

Abstract Background Whole-genome sequencing has shown that the Mycobacterium tuberculosis infection process can be more heterogeneous than previously thought. Compartmentalized infections, exogenous reinfections, and microevolution are manifestations of this clonal complexity. The analysis of the mechanisms causing the microevolution —the genetic variability of M. tuberculosis at short time scales— of a parental strain into clonal variants with a patient is a relevant issue that has not been yet completely addressed. To our knowledge, a whole genome sequence microevolution analysis in a single patient with inadequate adherence to treatment has not been previously reported. Case presentation In this work, we applied whole genome sequencing analysis for a more in-depth analysis of the microevolution of a parental Mycobacterium tuberculosis strain into clonal variants within a patient with poor treatment compliance in Argentina. We analyzed the whole-genome sequence of 8 consecutive Mycobacterium tuberculosis isolates obtained from a patient within 57-months of intermittent therapy. Nineteen mutations (9 short-term, 10 fixed variants) emerged, most of them associated with drug resistance. The first isolate was already resistant to isoniazid, rifampicin, and streptomycin, thereafter the strain developed resistance to fluoroquinolones and pyrazinamide. Surprisingly, isolates remained susceptible to the pro-drug ethionamide after acquiring a frameshift mutation in ethA, a gene required for its activation. We also found a novel variant, (T-54G), in the 5′ untranslated region of whiB7 (T-54G), a region allegedly related to kanamycin resistance. Notably, discrepancies between canonical and phage-based susceptibility testing to kanamycin were previously found for the isolate harboring this mutation. In our patient, microevolution was mainly driven by drug selective pressure. Rare short-term mutations fixed together with resistance-conferring mutations during therapy. Conclusions This report highlights the relevance of whole-genome sequencing analysis in the clinic for characterization of pre-XDR and MDR resistance profile, particularly in patients with incomplete and/or intermittent treatment.

scholarly journals Whole-Genome Sequence of Streptococcus tigurinus Strain osk_001, Isolated from Postmortem Material

2017 ◽  
Vol 5 (35) ◽  
Author(s):  
Hidenori Yoshizawa ◽  
Daisuke Motooka ◽  
Ryuichi Katada ◽  
Yuki Matsumoto ◽  
Shota Nakamura ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Novel Species ◽  
Infected Tissue ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Virulent Strains ◽  
Highly Virulent

ABSTRACT Streptococcus tigurinus was recently described as a novel species, and some strains are highly virulent. We detected S. tigurinus in infected tissue sampled by necropsy. In order to characterize and confirm the virulence of this species, whole-genome sequencing of the pure cultured bacterium was performed. We found that the strain has specific and unique genetic elements contained in highly virulent strains of S. tigurinus.

scholarly journals Whole-Genome Sequence of the Mycoplasma mucosicanis Type Strain

2019 ◽  
Vol 8 (41) ◽  
Author(s):  
Rebecca L. Tallmadge ◽  
Patrick K. Mitchell ◽  
Renee Anderson ◽  
Rebecca Franklin-Guild ◽  
Laura B. Goodman
Keyword(s):  
Whole Genome Sequencing ◽  
Clinical Significance ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Diagnostic Tests ◽  
Type Strain ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type

Whole-genome sequencing of Mycoplasma mucosicanis type strain 1642 was performed to support efforts to better understand the clinical significance of Mycoplasma infection in canine health. The availability of this sequence will also further the development of highly specific diagnostic tests.

scholarly journals Advanced whole genome sequencing and analysis of fetal genomes from amniotic fluid

2017 ◽  
Author(s):  
Qing Mao ◽  
Robert Chin ◽  
Weiwei Xie ◽  
Yuqing Deng ◽  
Huixin Xu ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Amniotic Fluid ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Chromosomal Abnormalities ◽  
Autism Spectrum ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
First Time

Amniocentesis is typically performed to identify large chromosomal abnormalities within the fetus. Here we demonstrate that it is feasible to generate an accurate whole genome sequence (WGS) of a fetus from an amniotic sample. DNA from cells and the amniotic fluid were isolated and sequenced from 31 amniocenteses. Concordance of variant calls between the two DNA sources and with parental libraries was high. Two fetal genomes were found to harbor potentially detrimental variants in CHD8 and LRP1, variations in these genes have been associated with Autism Spectrum Disorder (ASD) and Keratosis pilaris atrophicans, respectively. We also discovered drug sensitivities and carrier information of fetuses for a variety of diseases. In this study, we demonstrate for the first time the sequencing of the whole genome of fetuses from amniotic fluid and show that much more information than large chromosomal abnormalities can be gained from an amniocentesis.

scholarly journals Whole-Genome Sequencing of Pantoea sp. Strain RIT388, a Potential Oral Opportunistic Pathogen Isolated from a Chewing Stick (Distemonanthus benthamianus)

2020 ◽  
Vol 9 (9) ◽  
Author(s):  
Han Ming Gan ◽  
Anutthaman Parthasarathy ◽  
Kurtis R. Henry ◽  
Michael A. Savka ◽  
Bolaji N. Thomas ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Antibacterial Properties ◽  
Opportunistic Pathogen ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Chewing Sticks

In this study, we report the isolation, identification, characterization, and whole-genome sequence of the endophyte Pantoea sp. strain RIT388, isolated from Distemonanthus benthamianus, a plant known for its antifungal and antibacterial properties that is commonly used for chewing sticks.

scholarly journals A Deep-Sequencing Workflow for the Fast and Efficient Generation of High-Quality African Swine Fever Virus Whole-Genome Sequences

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 846 ◽  
Author(s):  
Jan Forth ◽  
Leonie Forth ◽  
Jacqueline King ◽  
Oxana Groza ◽  
Alexandra Hübner ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Genome Sequences ◽  
High Quality

African swine fever (ASF) is a severe disease of suids caused by African swine fever virus (ASFV). Its dsDNA genome (170–194 kbp) is scattered with homopolymers and repeats as well as inverted-terminal-repeats (ITR), which hamper whole-genome sequencing. To date, only a few genome sequences have been published and only for some are data on sequence quality available enabling in-depth investigations. Especially in Europe and Asia, where ASFV has continuously spread since its introduction into Georgia in 2007, a very low genetic variability of the circulating ASFV-strains was reported. Therefore, only whole-genome sequences can serve as a basis for detailed virus comparisons. Here, we report an effective workflow, combining target enrichment, Illumina and Nanopore sequencing for ASFV whole-genome sequencing. Following this approach, we generated an improved high-quality ASFV Georgia 2007/1 whole-genome sequence leading to the correction of 71 sequencing errors and the addition of 956 and 231 bp at the respective ITRs. This genome, derived from the primary outbreak in 2007, can now serve as a reference for future whole-genome analyses of related ASFV strains and molecular approaches. Using both workflow and the reference genome, we generated the first ASFV-whole-genome sequence from Moldova, expanding the sequence knowledge from Eastern Europe.

scholarly journals Whole-Genome Sequence of Chryseobacterium oranimense, a Colistin-Resistant Bacterium Isolated from a Cystic Fibrosis Patient in France

2015 ◽  
Vol 59 (3) ◽  
pp. 1696-1706 ◽  
Author(s):  
Poonam Sharma ◽  
Sushim Kumar Gupta ◽  
Seydina M. Diene ◽  
Jean-Marc Rolain
Keyword(s):  
Cystic Fibrosis ◽  
Antibiotic Resistance ◽  
Whole Genome Sequencing ◽  
Cystic Fibrosis Patient ◽  
Genome Sequencing ◽  
Genome Sequence ◽  
Resistant Bacterium ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type

ABSTRACTFor the first time, we report the whole-genome sequence analysis ofChryseobacterium oranimenseG311, a multidrug-resistant bacterium, from a cystic fibrosis patient in France, including resistance to colistin. Whole-genome sequencing ofC. oranimenseG311 was performed using Ion Torrent PGM, and RAST, the EMBL-EBI server, and the Antibiotic Resistance Gene-ANNOTation (ARG-ANNOT) database were used for annotation of all genes, including antibiotic resistance (AR) genes. General features of theC. oranimenseG311 draft genome were compared to the other available genomes ofChryseobacterium gleumandChryseobacteriumsp. strain CF314.C. oranimenseG311 was found to be resistant to all β-lactams, including imipenem, and to colistin. The genome size ofC. oranimenseG311 is 4,457,049 bp in length, with 37.70% GC content. We found 27 AR genes in the genome, including β-lactamase genes which showed little similarity to the known β-lactamase genes and could likely be novel. We found the type I polyketide synthase operon followed by a zeaxanthin glycosyltransferase gene in the genome, which could impart the yellow pigmentation of the isolate. We located the O-antigen biosynthesis cluster, and we also discovered a novel capsular polysaccharide biosynthesis cluster. We also found known mutations in the orthologs of thepmrA(E8D),pmrB(L208F and P360Q), andlpxA(G68D) genes. We speculate that the presence of the capsular cluster and mutations in these genes could explain the resistance of this bacterium to colistin. We demonstrate that whole-genome sequencing was successfully applied to decipher the resistome of a multidrug resistance bacterium associated with cystic fibrosis patients.

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