scholarly journals Fast computation of a string duplication history under no-breakpoint-reuse

Author(s):  
Broňa Brejová ◽  
Martin Kravec ◽  
Gad M. Landau ◽  
Tomáš Vinař

In this paper, we provide an O ( n log 2 n log log n log* n ) algorithm to compute a duplication history of a string under no-breakpoint-reuse condition. The motivation of this problem stems from computational biology, in particular, from analysis of complex gene clusters. The problem is also related to computing edit distance with block operations, but, in our scenario, the start of the history is not fixed, but chosen to minimize the distance measure.

2020 ◽  
Vol 105 (1) ◽  
pp. 55-66
Author(s):  
Wolfgang Hüttel

Abstract Echinocandins are a clinically important class of non-ribosomal antifungal lipopeptides produced by filamentous fungi. Due to their complex structure, which is characterized by numerous hydroxylated non-proteinogenic amino acids, echinocandin antifungal agents are manufactured semisynthetically. The development of optimized echinocandin structures is therefore closely connected to their biosynthesis. Enormous efforts in industrial research and development including fermentation, classical mutagenesis, isotope labeling, and chemical synthesis eventually led to the development of the active ingredients caspofungin, micafungin, and anidulafungin, which are now used as first-line treatments against invasive mycosis. In the last years, echinocandin biosynthetic gene clusters have been identified, which allowed for the elucidation but also engineering of echinocandin biosynthesis on the molecular level. After a short description of the history of echinocandin research, this review provides an overview of the current knowledge of echinocandin biosynthesis with a special focus of the diverse structural elements, their biosynthetic background, and structure−activity relationships. Key points • Complex and highly oxidized lipopeptides produced by fungi. • Crucial in the design of drugs: side chain, solubility, and hydrolytic stability. • Genetic methods for engineering biosynthesis have recently become available.


2020 ◽  
pp. 030573562097103
Author(s):  
Matthew Moritz ◽  
Matthew Heard ◽  
Hyun-Woong Kim ◽  
Yune S Lee

Despite the long history of music psychology, rhythm similarity perception remains largely unexplored. Several studies suggest that edit-distance—the minimum number of notational changes required to transform one rhythm into another—predicts similarity judgments. However, the ecological validity of edit-distance remains elusive. We investigated whether the edit-distance model can predict perceptual similarity between rhythms that also differed in a fundamental characteristic of music—tempo. Eighteen participants rated the similarity between a series of rhythms presented in a pairwise fashion. The edit-distance of these rhythms varied from 1 to 4, and tempo was set at either 90 or 150 beats per minute (BPM). A test of congruence among distance matrices (CADM) indicated significant inter-participant reliability of ratings, and non-metric multidimensional scaling (nMDS) visualized that the ratings were clustered based upon both tempo and whether rhythms shared an identical onset pattern, a novel effect we termed rhythm primacy. Finally, Mantel tests revealed significant correlations of edit-distance with similarity ratings on both within- and between-tempo rhythms. Our findings corroborated that the edit-distance predicts rhythm similarity and demonstrated that the edit-distance accounts for similarity of rhythms that are markedly different in tempo. This suggests that rhythmic gestalt is invariant to differences in tempo.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 219-219 ◽  
Author(s):  
Ruchira Sood ◽  
Erin Gourley ◽  
Stanley L. Schrier ◽  
Ronald Go ◽  
James L. Zehnder

Abstract Cyclic thrombocytopenia (CTP) is a rare disorder characterized by periodic changes in platelet count. While some previous reports suggest an association with several cytokines, the etiology of this disorder remains poorly characterized. Using DNA microarrays, we examined the gene expression profile in peripheral whole blood at multiple time points encompassing a cycle of platelet counts from two CTP patients. We hypothesized that the variation in gene expression program in whole blood would reflect on the transcriptional changes associated with or perhaps even underlying this disease. Genome-wide cDNA microarray analysis was performed using amplified RNA obtained from 11 and 8 whole blood samples from each patient. The first patient is a 41-year old male with a 2-year history of CTP while the second patient is a 54-year old male with a 3-year history of CTP. The period of both patients’ cycles is roughly 3 weeks. No associated underlying disease has been found in both patients. With a focus on 1500 genes that change 3 fold within each group of samples we observed clusters of gene expression in whole blood that correlate with changing platelet numbers in both patients. Significant variation in expression of a cluster of interferon responsive genes during the platelet count cycle was particularly striking in both samples. Interferon (IFN) therapy is known to suppress platelet counts, and this observation suggests that aberrant IFN levels and signalling could be in part responsible for CTP. At high platelet counts, platelet transcripts were detected in whole blood RNA as inferred by high expression of previously described platelet genes including TBXAS1, TUBB1, OAZ1, SEPT5, several mitochondrial genes, NRGN and F13A1. In addition, gene clusters including known genes as well as previously uncharacterized genes were found to correlate with the peak, increasing or decreasing trends of platelet counts. Briefly, GATA2 and NFE2 expression coincided with the platelet count peak, while Tyk2 and SOCS5 expression was consistent with a rising trend of platelet counts and GATA3 and JAK2 coincided with decreasing trend of platelet counts. These results show gene expression changes associated with CTP in all cell types in whole blood and pave the way for new investigation into regulation of platelet number in a rare and fascinating disease. Gene expression profile of whole blood of two CTP patients with platelet counts ranging from high to low and then increasing again from left to right of each panel Gene expression profile of whole blood of two CTP patients with platelet counts ranging from high to low and then increasing again from left to right of each panel


mSphere ◽  
2016 ◽  
Vol 1 (4) ◽  
Author(s):  
Timothy J. Johnson ◽  
Jessica L. Danzeisen ◽  
Bonnie Youmans ◽  
Kyle Case ◽  
Katharine Llop ◽  
...  

ABSTRACT A clonal lineage of Escherichia coli known as ST131 has emerged as a dominating strain type causing extraintestinal infections in humans. The evolutionary history of ST131 E. coli is now well understood. However, the role of plasmids in ST131’s evolutionary history is poorly defined. This study utilized real-time, single-molecule sequencing to compare plasmids from various current and historical lineages of ST131. From this work, it was determined that a series of plasmid gains, losses, and recombinational events has led to the currently circulating plasmids of ST131 strains. These plasmids appear to have evolved to acquire similar gene clusters on multiple occasions, suggesting possible plasmid-mediated convergent evolution leading to evolutionary success. These plasmids also appear to be better suited to exist in specific strains of ST131 due to coadaptive mutations. Overall, a series of events has enabled the evolution of ST131 plasmids, possibly contributing to the lineage’s success. The extraintestinal pathogenic Escherichia coli (ExPEC) H30 subclone of sequence type 131 (ST131-H30) has emerged abruptly as a dominant lineage of ExPEC responsible for human disease. The ST131-H30 lineage has been well described phylogenetically, yet its plasmid complement is not fully understood. Here, single-molecule, real-time sequencing was used to generate the complete plasmid sequences of ST131-H30 isolates and those belonging to other ST131 clades. Comparative analyses revealed separate F-type plasmids that have shaped the evolution of the main fluoroquinolone-resistant ST131-H30 clades. Specifically, an F1:A2:B20 plasmid is strongly associated with the H30R/C1 clade, whereas an F2:A1:B− plasmid is associated with the H30Rx/C2 clade. A series of plasmid gene losses, gains, and rearrangements involving IS26 likely led to the current plasmid complements within each ST131-H30 sublineage, which contain several overlapping gene clusters with putative functions in virulence and fitness, suggesting plasmid-mediated convergent evolution. Evidence suggests that the H30Rx/C2-associated F2:A1:B− plasmid type was present in strains ancestral to the acquisition of fluoroquinolone resistance and prior to the introduction of a multidrug resistance-encoding gene cassette harboring bla CTX-M-15. In vitro experiments indicated a host strain-independent low frequency of plasmid transfer, differential levels of plasmid stability even between closely related ST131-H30 strains, and possible epistasis for carriage of these plasmids within the H30R/Rx lineages. IMPORTANCE A clonal lineage of Escherichia coli known as ST131 has emerged as a dominating strain type causing extraintestinal infections in humans. The evolutionary history of ST131 E. coli is now well understood. However, the role of plasmids in ST131’s evolutionary history is poorly defined. This study utilized real-time, single-molecule sequencing to compare plasmids from various current and historical lineages of ST131. From this work, it was determined that a series of plasmid gains, losses, and recombinational events has led to the currently circulating plasmids of ST131 strains. These plasmids appear to have evolved to acquire similar gene clusters on multiple occasions, suggesting possible plasmid-mediated convergent evolution leading to evolutionary success. These plasmids also appear to be better suited to exist in specific strains of ST131 due to coadaptive mutations. Overall, a series of events has enabled the evolution of ST131 plasmids, possibly contributing to the lineage’s success.


Author(s):  
Yu Zhang ◽  
Giltae Song ◽  
Tomáš Vinař ◽  
Eric D. Green ◽  
Adam Siepel ◽  
...  

2005 ◽  
Vol 16 (06) ◽  
pp. 1231-1251 ◽  
Author(s):  
LILI ZHANG ◽  
F. BLANCHET-SADRI

Computing approximate patterns in strings or sequences has important applications in DNA sequence analysis, data compression, musical text analysis, and so on. In this paper, we introduce approximate k-covers and study them under various commonly used distance measures. We propose the following problem: "Given a string x of length n, a set U of m strings of length k, and a distance measure, compute the minimum number t such that U is a set of approximate k-covers for x with distance t". To solve this problem, we present three algorithms with time complexity O(km(n - k)), O(mn2) and O(mn2) under Hamming, Levenshtein and edit distance, respectively. A World Wide Web server interface has been established at for automated use of the programs.


Author(s):  
David B. Blumenthal ◽  
Johann Gamper ◽  
Sébastien Bougleux ◽  
Luc Brun

The graph edit distance (GED) is a flexible distance measure which is widely used for inexact graph matching. Since its exact computation is [Formula: see text]-hard, heuristics are used in practice. A popular approach is to obtain upper bounds for GED via transformations to the linear sum assignment problem with error-correction (LSAPE). Typically, local structures and distances between them are employed for carrying out this transformation, but recently also machine learning techniques have been used. In this paper, we formally define a unifying framework LSAPE-GED for transformations from GED to LSAPE. We also introduce rings, a new kind of local structures designed for graphs where most information resides in the topology rather than in the node labels. Furthermore, we propose two new ring-based heuristics RING and RING-ML, which instantiate LSAPE-GED using the traditional and the machine learning-based approach for transforming GED to LSAPE, respectively. Extensive experiments show that using rings for upper bounding GED significantly improves the state of the art on datasets where most information resides in the graphs’ topologies. This closes the gap between fast but rather inaccurate LSAPE-based heuristics and more accurate but significantly slower GED algorithms based on local search.


2020 ◽  
Author(s):  
Wei Lin ◽  
Wensi Zhang ◽  
Greig A. Paterson ◽  
Qiyun Zhu ◽  
Xiang Zhao ◽  
...  

AbstractThe discovery of membrane-enclosed, metabolically functional organelles in Bacteria and Archaea has transformed our understanding of the subcellular complexity of prokaryotic cells. However, whether prokaryotic organelles emerged early or late in evolutionary history remains unclear and limits understanding of the nature and cellular complexity of early life. Biomineralization of magnetic nanoparticles within magnetosomes by magnetotactic bacteria (MTB) is a fascinating example of prokaryotic organelles. Here, we reconstruct 168 metagenome-assembled MTB genomes from various aquatic environments and waterlogged soils. These genomes represent nearly a 3-fold increase over the number currently available, and more than double the known MTB species. Phylogenomic analysis reveals that these newly described genomes belong to 13 Bacterial phyla, six of which were previously not known to include MTB. These findings indicate a much wider taxonomic distribution of magnetosome organelle biogenesis across the domain Bacteria than previously thought. Comparative genome analysis reveals a vast diversity of magnetosome gene clusters involved in magnetosomal biogenesis in terms of gene content and synteny residing in distinct taxonomic lineages. These gene clusters therefore represent a promising, diverse genetic resource for biosynthesizing novel magnetic nanoparticles. Finally, our phylogenetic analyses of the core magnetosome proteins in this largest available and taxonomically diverse dataset support an unexpectedly early evolutionary origin of magnetosome biomineralization, likely ancestral to the origin of the domain Bacteria. These findings emphasize the potential biological significance of prokaryotic organelles on the early Earth and have important implications for our understanding of the evolutionary history of cellular complexity.


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