Hidden breakpoints in genome alignments

During the course of evolution, an organism's genome can undergo changes that affect the large-scale structure of the genome. These changes include gene gain, loss, duplication, chromosome fusion, fission, and rearrangement. When gene gain and loss occurs in addition to other types of rearrangement, breakpoints of rearrangement can exist that are only detectable by comparison of three or more genomes. An arbitrarily large number of these "hidden" breakpoints can exist among genomes that exhibit no rearrangements in pairwise comparisons. We present an extension of the multichromosomal breakpoint median problem to genomes that have undergone gene gain and loss. We then demonstrate that the median distance among three genomes can be used to calculate a lower bound on the number of hidden breakpoints present. We provide an implementation of this calculation including the median distance, along with some practical improvements on the time complexity of the underlying algorithm. We apply our approach to measure the abundance of hidden breakpoints in simulated data sets under a wide range of evolutionary scenarios. We demonstrate that in simulations the hidden breakpoint counts depend strongly on relative rates of inversion and gene gain/loss. Finally we apply current multiple genome aligners to the simulated genomes, and show that all aligners introduce a high degree of error in hidden breakpoint counts, and that this error grows with evolutionary distance in the simulation. Our results suggest that hidden breakpoint error may be pervasive in genome alignments.Comment: 13 pages, 4 figure

Explosive Percolation in the Human Protein Homology Network

We study the explosive character of the percolation transition in a real-world network. We show that the emergence of a spanning cluster in the Human Protein Homology Network (H-PHN) exhibits similar features to an Achlioptas-type process and is markedly different from regular random percolation. The underlying mechanism of this transition can be described by slow-growing clusters that remain isolated until the later stages of the process, when the addition of a small number of links leads to the rapid interconnection of these modules into a giant cluster. Our results indicate that the evolutionary-based process that shapes the topology of the H-PHN through duplication-divergence events may occur in sudden steps, similarly to what is seen in first-order phase transitions.Comment: 13 pages, 6 figure

Structural mechanism for the recognition and ubiquitination of a single nucleosome residue by Rad6-Bre1

Cotranscriptional ubiquitination of histone H2B is key to gene regulation. The yeast E3 ubiquitin ligase Bre1 (human RNF20/40) pairs with the E2 ubiquitin conjugating enzyme Rad6 to monoubiquitinate H2B at Lys123. How this single lysine residue on the nucleosome core particle (NCP) is targeted by the Rad6-Bre1 machinery is unknown. Using chemical cross-linking and mass spectrometry, we identified the functional interfaces of Rad6, Bre1, and NCPs in a defined in vitro system. The Bre1 RING domain cross-links exclusively with distinct regions of histone H2B and H2A, indicating a spatial alignment of Bre1 with the NCP acidic patch. By docking onto the NCP surface in this distinct orientation, Bre1 positions the Rad6 active site directly over H2B Lys123. The Spt-Ada-Gcn5 acetyltransferase (SAGA) H2B deubiquitinase module competes with Bre1 for binding to the NCP acidic patch, indicating regulatory control. Our study reveals a mechanism that ensures site-specific NCP ubiquitination and fine-tuning of opposing enzymatic activities

Pseudoclavibacter-like subcutaneous infection: a case report

<p>Abstract</p> <p>Background</p> <p><it>Arthrobacter</it>-like organisms, including <it>Pseudoclavibacter </it>organisms, have rarely been documented as being responsible for infection in humans.</p> <p>Case presentation</p> <p>An 81-year-old French man developed a subcutaneous infection despite antibiotic treatment combining clindamycin and metronidazole for chronic wound infection. A skin biopsy showed numerous polymorphonuclear cells and no bacteria, but a subcutaneous swab yielded numerous polymorphonuclear cells, a few Gram-positive cocci, Gram-negative cocci, and Gram-positive rods. The Gram-positive rod sequence exhibited 99% sequence similarity with uncultured <it>Pseudoclavibacter </it>sp. [GenBank:<ext-link ext-link-id="EF419350" ext-link-type="gen">EF419350</ext-link>] and 99% sequence similarity with uncultured <it>Pseudoclavibacter </it>sp. [GenBank:<ext-link ext-link-id="EF419347" ext-link-type="gen">EF419347</ext-link>]. The genetic data and unique peptide profile of this <it>Pseudoclavibacter</it>-like isolate, determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry, underscored its uniqueness.</p> <p>Conclusions</p> <p><it>Pseudoclavibacter</it>-like organisms are identifiable in cutaneous and subcutaneous infections in humans.</p

Electrochemical integration of graphene with light absorbing copper-based thin films

We present an electrochemical route for the integration of graphene with light sensitive copper-based alloys used in optoelectronic applications. Graphene grown using chemical vapor deposition (CVD) transferred to glass is found to be a robust substrate on which photoconductive Cu_{x}S films of 1-2 um thickness can be deposited. The effect of growth parameters on the morphology and photoconductivity of Cu_{x}S films is presented. Current-voltage characterization and photoconductivity decay experiments are performed with graphene as one contact and silver epoxy as the other

Growth performance, in vitro antioxidant properties and chemical composition of the halophyte Limonium algarvense Erben are strongly influenced by the irrigation salinity

Limonium algarvense Erben (sea lavender) is a halophyte species with potential to provide natural ingredients with in vitro antioxidant, anti-inflammatory, neuroprotective and antidiabetic properties. This study reports for the first time the 1) cultivation of sea lavender in greenhouse conditions under irrigation with freshwater (approx. 0 mM NaCl) and saline aquaculture wastewater (300 and 600 mM NaCl), and 2) the influence of the irrigation salinity on the plant performance (e.g growth, number of produced leaves and flowers), in vitro antioxidant properties [radical scavenging activity (DPPH and ABTS), ferric reducing antioxidant power (FRAP), metal chelating properties on copper (CCA) and iron (ICA)], toxicity (in vitro on three mammalian cell lines) and chemical composition (determined by LC-ESI-HRMS/MS). The freshwater-irrigated plants had better growth performance than those irrigated with saltwater. Extracts from wild plants, had the highest antioxidant activity, but those from cultivated ones kept high in vitro antioxidant properties and interesting chemical profile. The flowers' extracts of plants irrigated with 300 mM NaCl had the highest antioxidant activities against DPPH, whereas those from freshwater-irrigated plants were more active on ABTS, CCA and FRAP. Most of the extracts showed nil toxicity. The flowers' extracts displayed the highest diversity of compounds, mainly quercetin, apigenin, luteolin, naringenin and their glycoside derivatives. Moreover, their abundance varied with the irrigation salinity. These data indicate that sea lavender plants can be successfully cultivated in greenhouse conditions under fresh- and saltwater irrigation, maintaining interesting biological and chemical properties.Funding Agency Portuguese Foundation for Science and Technology Portuguese National Budget CCMAR/Multi/04326/2019 GreenVet project ALG-01-0145-FEDER-028876 XtrerneAquaCrops FA-05-2017-028 Lisboa-01-0145-FEDER-022125-RNEM-IST ID/QUI/00100/201 Portuguese Foundation for Science and Technology SFRH/BD/116604/2016 CEECIND/00425/2017info:eu-repo/semantics/publishedVersio

Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

Efficient oligonucleotide probe selection for pan-genomic tiling arrays

Background: Array comparative genomic hybridization is a fast and cost-effective method for detecting, genotyping, and comparing the genomic sequence of unknown bacterial isolates. This method, as with all microarray applications, requires adequate coverage of probes targeting the regions of interest. An unbiased tiling of probes across the entire length of the genome is the most flexible design approach. However, such a whole-genome tiling requires that the genome sequence is known in advance. For the accurate analysis of uncharacterized bacteria, an array must query a fully representative set of sequences from the species' pan-genome. Prior microarrays have included only a single strain per array or the conserved sequences of gene families. These arrays omit potentially important genes and sequence variants from the pan-genome. Results: This paper presents a new probe selection algorithm (PanArray) that can tile multiple whole genomes using a minimal number of probes. Unlike arrays built on clustered gene families, PanArray uses an unbiased, probe-centric approach that does not rely on annotations, gene clustering, or multi-alignments. Instead, probes are evenly tiled across all sequences of the pangenome at a consistent level of coverage. To minimize the required number of probes, probes conserved across multiple strains in the pan-genome are selected first, and additional probes are used only where necessary to span polymorphic regions of the genome. The viability of the algorithm is demonstrated by array designs for seven different bacterial pan-genomes and, in particular, the design of a 385,000 probe array that fully tiles the genomes of 20 different Listeria monocytogenes strains with overlapping probes at greater than twofold coverage. Conclusion: PanArray is an oligonucleotide probe selection algorithm for tiling multiple genome sequences using a minimal number of probes. It is capable of fully tiling all genomes of a species on a single microarray chip. These unique pan-genome tiling arrays provide maximum flexibility for the analysis of both known and uncharacterized strains.https://doi.org/10.1186/1471-2105-10-29

BPGA- an ultra-fast pan-genome analysis pipeline

Recent advances in ultra-high-throughput sequencing technology and metagenomics have led to a paradigm shift in microbial genomics from few genome comparisons to large-scale pan-genome studies at different scales of phylogenetic resolution. Pan-genome studies provide a framework for estimating the genomic diversity of the dataset, determining core (conserved), accessory (dispensable) and unique (strain-specific) gene pool of a species, tracing horizontal gene-flux across strains and providing insight into species evolution. The existing pan genome software tools suffer from various limitations like limited datasets, difficult installation/requirements, inadequate functional features etc. Here we present an ultra-fast computational pipeline BPGA (Bacterial Pan Genome Analysis tool) with seven functional modules. In addition to the routine pan genome analyses, BPGA introduces a number of novel features for downstream analyses like core/pan/MLST (Multi Locus Sequence Typing) phylogeny, exclusive presence/absence of genes in specific strains, subset analysis, atypical G + C content analysis and KEGG & COG mapping of core, accessory and unique genes. Other notable features include minimum running prerequisites, freedom to select the gene clustering method, ultra-fast execution, user friendly command line interface and high-quality graphics outputs. The performance of BPGA has been evaluated using a dataset of complete genome sequences of 28 Streptococcus pyogenes strains

Combined use of gliadins and SSRs to analyse the genetic variability of the Spanish collection of cultivated diploid wheat (Triticum monococcum L. ssp. monococcum)

This work studied the combined use of gliadins and SSRs to analyse inter- and intra-accession variability of the Spanish collection of cultivated einkorn (Triticum monococcum L. ssp. monococcum) maintained at the CRF-INIA. In general, gliadin loci presented higher discrimination power than SSRs, reflecting the high variability of the gliadins. The loci on chromosome 6A were the most polymorphic with similar PIC values for both marker systems, showing that these markers are very useful for genetic variability studies in wheat. The gliadin results indicated that the Spanish einkorn collection possessed high genetic diversity, being the differentiation large between varieties and small within them. Some associations between gliadin alleles and geographical and agro-morphological data were found. Agro-morphological relations were also observed in the clusters of the SSRs dendrogram. A high concordance was found between gliadins and SSRs for genotype identification. In addition, both systems provide complementary information to resolve the different cases of intra-accession variability not detected at the agro-morphological level, and to identify separately all the genotypes analysed. The combined use of both genetic markers is an excellent tool for genetic resource evaluation in addition to agro-morphological evaluation