scholarly journals panModule: detecting conserved modules in the variable regions of a pangenome graph

2021 ◽  
Author(s):  
Adelme Bazin ◽  
Claudine Medigue ◽  
David Vallenet ◽  
Alexandra Calteau

The recent years have seen the rise of pangenomes as comparative genomic tools to better understand the evolution of gene content among microbial genomes in close phylogenetic groups such as species. While the core or persistent genome is often well-known as it includes essential or ubiquitous genes, the variable genome is usually less characterized and includes many genes with unknown functions even among the most studied organisms. It gathers important genes for strain adaptation that are acquired by horizontal gene transfer. Here, we introduce panModule, an original method to identify conserved modules in pangenome graphs built from thousands of microbial genomes. These modules correspond to synteny blocks composed of consecutive genes that are conserved in a subset of the compared strains. Identifying conserved modules can provide insights on genes involved in the same functional processes, and as such is a very helpful tool to facilitate the understanding of genomic regions with complex evolutionary histories. The panModule method was benchmarked on a curated dataset of conserved modules in Escherichia coli genomes. Its use was illustrated through a study of a high pathogenicity island in Klebsiella pneumoniae that allowed a better understanding of this region. panModule is freely available and accessible through the PPanGGOLiN software suite (https://github.com/labgem/PPanGGOLiN).

2017 ◽  
Author(s):  
Wei Zhou ◽  
Nicole Gay ◽  
Julia Oh

AbstractBackgroundProfiling of shotgun metagenomic samples is hindered by a lack of unified microbial reference genome databases that i) assemble genomic information from all open access microbial genomes, ii) have relatively small sizes, and iii) are compatible to various metagenomic read mapping tools. Moreover, computational tools to rapidly compile and update such databases to accommodate the rapid increase in new reference genomes do not exist. As a result, database-guided analyses often fail to profile a substantial fraction of metagenomic shotgun sequencing reads from complex microbiomes.ResultsWe report pipelines that efficiently traverse all open access microbial genomes and assemble non-redundant genomic information. The pipelines result in two species-resolution microbial reference databases of relatively small sizes: reprDB, which assembles microbial representative or reference genomes, and panDB, for which we developed a novel iterative alignment algorithm to identify and assemble non-redundant genomic regions in multiple sequenced strains. With the databases, we managed to assign taxonomic labels and genome positions to the majority of metagenomic reads from human skin and gut microbiomes, demonstrating a significant improvement over a previous database-guided analysis on the same datasets.ConclusionsreprDB and panDB leverage the rapid increases in the number of open access microbial genomes to more fully profile metagenomic samples. Additionally, the databases exclude redundant sequence information to avoid inflated storage or memory space and indexing or analyses time. Finally, the novel iterative alignment algorithm significantly increases efficiency in pan-genome identification and can be useful in comparative genomic analyses.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Miao-Miao Zhang ◽  
Jun-Wei Zhao ◽  
Zhan-Qiang Sun ◽  
Jun Liu ◽  
Xiao-Kui Guo ◽  
...  

Comparative genomic studies have identified severalMycobacterium tuberculosis-specific genomic regions of difference (RDs) which are absent in the vaccine strains ofMycobacterium bovisBCG and which may be useful in the specific diagnosis of tuberculosis (TB). In this study, all encoded proteins from DNA segment RD5 ofMycobacterium tuberculosis, that is, Rv3117–Rv3121, were recombined and evaluated by enzyme-linked immunosorbent assays for antibody reactivity with sera from HIV-negative pulmonary TB patients (n=60) and healthy controls (n=32). The results identified two immunodominant antigens, that is, Rv3117 and Rv3120, both of which revealed a statistically significant antigenic distinction between healthy controls and TB patients (P<0.05). In comparison with the well-known early-secreted antigen target 6 kDa (ESAT-6) (sensitivity 21.7%, specificity 90.6%), the higher detection sensitivity and higher specificity were achieved (Rv3117: sensitivity 25%, specificity 96.9%; Rv3120: sensitivity 31.7%, specificity 96.9%). Thus, the results highlight the immunosensitive and immunospecific nature of Rv3117 and Rv3120 and indicate promise for their use in the serodiagnosis of TB.


2010 ◽  
Vol 18 (3) ◽  
pp. 477-482 ◽  
Author(s):  
Noora Y. Al-Khodari ◽  
Rajaa Al-Attiyah ◽  
Abu S. Mustafa

ABSTRACTComparative genomic studies have identified severalMycobacterium tuberculosis-specific genomic regions of difference (RDs) which are absent in the vaccine strains ofMycobacterium bovisBCG and which may be useful in the specific diagnosis of tuberculosis (TB). In this study, a total of 775 synthetic peptides covering the sequences of 39 open reading frame (ORF) proteins encoded by genes predicted in five RDs ofM. tuberculosis, i.e., RD1, RD4, RD5, RD6, and RD7, were tested by enzyme-linked immunosorbent assays for antibody reactivity with sera from HIV-negative pulmonary TB patients (n= 100) andM. bovisBCG-vaccinated healthy subjects (n= 100). The results identified three immunodominant peptides reactive with TB sera, i.e., amino acids (aa) 346 to 370 of RD1ORF Rv3876, aa 241 to 265 of RD6ORF Rv1508c, and aa 325 to 336 of RD6ORF Rv1516c. These peptides had significantly stronger antibody reactivity with sera from TB patients than with sera from healthy subjects (P< 0.05) and significantly higher rates of positivity with TB sera (positives = 66 to 93%) than sera from healthy subjects (positives = 10 to 28%). Antipeptide antibodies were raised in rabbits after immunization with pools of 11 peptides corresponding to each protein. Probing of culture filtrates and whole-cell lysates ofM. tuberculosiswith antipeptide antibodies suggested the natural expression of Rv1516c in whole-cell lysates ofM. tuberculosis. The results suggest the potential of the identified immunodominant RD peptides in the serodiagnosis of TB.


2020 ◽  
Vol 8 (3) ◽  
pp. 366
Author(s):  
Jarred Yasuhara-Bell ◽  
Mohammad Arif ◽  
Grethel Y. Busot ◽  
Rachel Mann ◽  
Brendan Rodoni ◽  
...  

Rathayibacter toxicus is a Gram-positive, nematode-vectored bacterium that infects several grass species in the family Poaceae. Unique in its genus, R. toxicus has the smallest genome, possesses a complete CRISPR-Cas system, a vancomycin-resistance cassette, produces tunicamycin, a corynetoxin responsible for livestock deaths in Australia, and is designated a Select Agent in the United States. In-depth, genome-wide analyses performed in this study support the previously designated five genetic populations, with a core genome comprising approximately 80% of the genome for all populations. Results varied as a function of the type of analysis and when using different bioinformatics tools for the same analysis; e.g., some programs failed to identify specific genomic regions that were actually present. The software variance highlights the need to verify bioinformatics results by additional methods; e.g., PCR, mapping genes to genomes, use of multiple algorithms). These analyses suggest the following relationships among populations: RT-IV ↔ RT-I ↔ RT-II ↔ RT-III ↔ RT-V, with RT-IV and RT-V being the most unrelated. This is the most comprehensive analysis of R. toxicus that included populations RT-I and RT-V. Future studies require underrepresented populations and more recent isolates from varied hosts and geographic locations.


Zootaxa ◽  
2020 ◽  
Vol 4748 (1) ◽  
pp. 182-194 ◽  
Author(s):  
JING ZHANG ◽  
ERNST BROCKMANN ◽  
QIAN CONG ◽  
JINHUI SHEN ◽  
NICK V. GRISHIN

We obtained whole genome shotgun sequences and phylogenetically analyzed protein-coding regions of representative skipper butterflies from the genus Carcharodus Hübner, [1819] and its close relatives. Type species of all available genus-group names were sequenced. We find that species attributed to four exclusively Old World genera (Spialia Swinhoe, 1912, Gomalia Moore, 1879, Carcharodus Hübner, [1819] and Muschampia Tutt, 1906) form a monophyletic group that we call a subtribe Carcharodina Verity, 1940. In the phylogenetic trees built from various genomic regions, these species form 7 (not 4) groups that we treat as genera. We find that Muschampia Tutt, 1906 is not monophyletic, and the 5th group is formed by currently monotypic genus Favria Tutt, 1906 new status (type species Hesperia cribrellum Eversmann, 1841), which is sister to Gomalia. The 6th and 7th groups are composed of mostly African species presently placed in Spialia. These groups do not have names and are described here as Ernsta Grishin, gen. n. (type species Pyrgus colotes Druce, 1875) and Agyllia Grishin, gen. n. (type species Pyrgus agylla Trimen, 1889). Two subgroups are recognized in Ernsta: the nominal subgenus and a new one: Delaga Grishin, subgen. n. (type species Pyrgus delagoae Trimen, 1898). Next, we observe that Carcharodus is not monophyletic, and species formerly placed in subgenera Reverdinus Ragusa, 1919 and Lavatheria Verity, 1940 are here transferred to Muschampia. Furthermore, due to differences in male genitalia or DNA sequences, we reinstate Gomalia albofasciata Moore, 1879 and Gomalia jeanneli (Picard, 1949) as species, not subspecies or synonyms of Gomalia elma (Trimen, 1862), and Spialia bifida (Higgins, 1924) as a species, not subspecies of Spialia zebra (Butler, 1888). Sequencing of the type specimens reveals 2.2-3.2% difference in COI barcodes, the evidence that combined with wing pattern differences suggests a new status of a species for Spialia lugens (Staudinger, 1886) and Spialia carnea (Reverdin, 1927), formerly subspecies of Spialia orbifer (Hübner, [1823]). 


2014 ◽  
Vol 171 (2) ◽  
pp. 253-262 ◽  
Author(s):  
Ana P M Canton ◽  
Sílvia S Costa ◽  
Tatiane C Rodrigues ◽  
Debora R Bertola ◽  
Alexsandra C Malaquias ◽  
...  

BackgroundThe etiology of prenatal-onset short stature with postnatal persistence is heterogeneous. Submicroscopic chromosomal imbalances, known as copy number variants (CNVs), may play a role in growth disorders.ObjectiveTo analyze the CNVs present in a group of patients born small for gestational age (SGA) without a known cause.Patients and methodsA total of 51 patients with prenatal and postnatal growth retardation associated with dysmorphic features and/or developmental delay, but without criteria for the diagnosis of known syndromes, were selected. Array-based comparative genomic hybridization was performed using DNA obtained from all patients. The pathogenicity of CNVs was assessed by considering the following criteria: inheritance; gene content; overlap with genomic coordinates for a known genomic imbalance syndrome; and overlap with CNVs previously identified in other patients with prenatal-onset short stature.ResultsIn 17 of the 51 patients, 18 CNVs were identified. None of these imbalances has been reported in healthy individuals. Nine CNVs, found in eight patients (16%), were categorized as pathogenic or probably pathogenic. Deletions found in three patients overlapped with known microdeletion syndromes (4q, 10q26, and 22q11.2). These imbalances are de novo, gene rich and affect several candidate genes or genomic regions that may be involved in the mechanisms of growth regulation.ConclusionPathogenic CNVs in the selected patients born SGA were common (at least 16%), showing that rare CNVs are probably among the genetic causes of short stature in SGA patients and revealing genomic regions possibly implicated in this condition.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Tomoyoshi Komiyama ◽  
Mengjie Lin ◽  
Atsushi Ogura

Chickens have been familiar to humans since ancient times and have been used not only for culinary purposes but also for cultural purposes including ritual ceremonies and traditional entertainment. The various chicken breeds developed for these purposes often display distinct morphological and/or behavioural traits. For example, the JapaneseShamois larger and more aggressive than other domesticated chickens, reflecting its role as a fighting cock breed, whereas JapaneseNaganakidoribreeds, which have long-crowing behaviour, were bred instead for their entertaining and aesthetic qualities. However, the genetic backgrounds of these distinct morphological and behavioural traits remain unclear. Therefore, the question arises as to which genomic regions in these chickens were acted upon by selective pressures through breeding. We compared the entire genomes of six chicken breeds domesticated for various cultural purposes by utilizing array comparative genomic hybridization. From these analyses, we identified 782 regions that underwent insertions, deletions, or mutations, representing man-made selection pressure in these chickens. Furthermore, we found that a number of genes diversified in domesticated chickens bred for cultural or entertainment purposes were different from those diversified in chickens bred for food, such as broilers and layers.


2011 ◽  
Vol 24 (4) ◽  
pp. 497-505 ◽  
Author(s):  
Bénédicte Coupat-Goutaland ◽  
Dominique Bernillon ◽  
Alice Guidot ◽  
Philippe Prior ◽  
Xavier Nesme ◽  
...  

Horizontal gene transfer (HGT) is a major driving force of evolution and is also likely to play an important role in the threatening emergence of novel pathogens, especially if it involves distantly related strains with substantially different pathogenicity. In this study, the impact of natural transformation on pathogenicity in six strains belonging to the four phylotypes of the plant-pathogenic bacterium Ralstonia solanacearum was investigated. The study focused on genomic regions that vary between donor and recipient strains and that carry genes involved in pathogenicity such as type III effectors. First, strains from R. solanacearum species complex were naturally transformed with heterologous genomic DNA. Transferred DNA regions were then determined by comparative genomic hybridization and polymerase chain reaction sequencing. We identified three transformant strains that acquired large DNA regions of up to 80 kb. In one case, strain Psi07 (phylotype IV tomato isolate) acquired 39.4 kb from GMI1000 (phylotype I tomato isolate). Investigations revealed that i) 24.4 kb of the acquired region contained 20 new genes, ii) an allelic exchange of 12 genes occurred, and iii) 27 genes (33.4 kb) formerly present in Psi07 were lost. Virulence tests with the three transformants revealed a significant increase in the aggressiveness of BCG20 over its Psi07 parent on tomato. These findings demonstrate the potential importance of HGT in the pathogenic evolution of R. solanacearum strains and open new avenues for studying pathogen emergence.


2016 ◽  
Vol 60 (10) ◽  
pp. 5933-5941 ◽  
Author(s):  
Lalena Wallace ◽  
Sean C. Daugherty ◽  
Sushma Nagaraj ◽  
J. Kristie Johnson ◽  
Anthony D. Harris ◽  
...  

ABSTRACTDespite the increasing prevalence of the nosocomial pathogenAcinetobacter baumannii, little is known about which genomic components contribute to clinical presentation of this important pathogen. Most whole-genome comparisons ofA. baumanniihave focused on specific genomic regions associated with phenotypes in a limited number of genomes. In this work, we describe the results of a whole-genome comparative analysis of 254 surveillance isolates ofAcinetobacterspecies, 203 of which wereA. baumannii, isolated from perianal swabs and sputum samples collected as part of an infection control active surveillance program at the University of Maryland Medical Center. The collection of surveillance isolates includes both carbapenem-susceptible and -resistant isolates. Based on the whole-genome phylogeny, theA. baumanniiisolates collected belong to two major phylogenomic lineages. Results from multilocus sequence typing indicated that one of the major phylogenetic groups ofA. baumanniiwas comprised solely of strains from the international clonal lineage 2. The genomic content of theA. baumanniiisolates was examined using large-scale BLAST score ratio analysis to identify genes that are associated with carbapenem-susceptible and -resistant isolates, as well as genes potentially associated with the source of isolation. This analysis revealed a number of genes that were exclusive or at greater frequency in each of these classifications. This study is the most comprehensive genomic comparison ofAcinetobacterisolates from a surveillance study to date and provides important information that will contribute to our understanding of the success ofA. baumanniias a human pathogen.


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