Chromosomal rearrangement inferred from comparisons of 12 Drosophila genomes

The availability of 12 complete genomes of various species of genus Drosophila provides a unique opportunity to analyze genome-scale chromosomal rearrangements among a group of closely related species. This article reports on the comparison of gene order between these 12 species and on the fixed rearrangement events that disrupt gene order. Three major themes are addressed: the conservation of syntenic blocks across species, the disruption of syntenic blocks (via chromosomal inversion events) and its relationship to the phylogenetic distribution of these species, and the rate of rearrangement events over evolutionary time. Comparison of syntenic blocks across this large genomic data set confirms that genetic elements are largely (95%) localized to the same Muller element across genus Drosophila species and paracentric inversions serve as the dominant mechanism for shuffling the order of genes along a chromosome. Gene-order scrambling between species is in accordance with the estimated evolutionary distances between them and we find it to approximate a linear process over time (linear to exponential with alternate divergence time estimates). We find the distribution of synteny segment sizes to be biased by a large number of small segments with comparatively fewer large segments. Our results provide estimated chromosomal evolution rates across this set of species on the basis of whole-genome synteny analysis, which are found to be higher than those previously reported. Identification of conserved syntenic blocks across these genomes suggests a large number of conserved blocks with varying levels of embryonic expression correlation in Drosophila melanogaster. On the other hand, an analysis of the disruption of syntenic blocks between species allowed the identification of fixed inversion breakpoints and estimates of breakpoint reuse and lineage-specific breakpoint event segregation.     

Genomic features in the breakpoint regions between syntenic blocks

MOTIVATION: We study the largely unaligned regions between the syntenic blocks conserved in humans and mice, based on data extracted from the UCSC genome browser. These regions contain evolutionary breakpoints caused by inversion, translocation and other processes. RESULTS: We suggest explanations for the limited amount of genomic alignment in the neighbourhoods of breakpoints. We discount inferences of extensive breakpoint reuse as artefacts introduced during the reconstruction of syntenic blocks. We find that the number, size and distribution of small aligned fragments in the breakpoint regions depend on the origin of the neighbouring blocks and the other blocks on the same chromosome. We account for this and for the generalized loss of alignment in the regions partially by artefacts due to alignment protocols and partially by mutational processes operative only after the rearrangement event. These results are consistent with breakpoints occurring randomly over virtually the entire genome.     

Genome association studies of complex diseases by case-control designs

One way to perform linkage-disequilibrium (LD) mapping of genetic traits is to use single markers. Since dense marker maps-such as single-nucleotide polymorphism and high-resolution microsatellite maps-are available, it is natural and practical to generalize single-marker LD mapping to high-resolution haplotype or multiple-marker LD mapping. This article investigates high-resolution LD-mapping methods, for complex diseases, based on haplotype maps or microsatellite marker maps. The objective is to explore test statistics that combine information from haplotype blocks or multiple markers. Based on two coding methods, genotype coding and haplotype coding, Hotelling's T2 statistics TG and TH are proposed to test the association between a disease locus and two haplotype blocks or two markers. The validity of the two T2 statistics is proved by theoretical calculations. A statistic TC, an extension of the traditional chi2 method of comparing haplotype frequencies, is introduced by simply adding the chi2 test statistics of the two haplotype blocks together. The merit of the three methods is explored by calculation and comparison of power and of type I errors. In the presence of LD between the two blocks, the type I error of TC is higher than that of TH and TG, since TC ignores the correlation between the two blocks. For each of the three statistics, the power of using two haplotype blocks is higher than that of using only one haplotype block. By power comparison, we notice that TC has higher power than that of TH, and TH has higher power than that of TG. In the absence of LD between the two blocks, the power of TC is similar to that of TH and higher than that of TG. Hence, we advocate use of TH in the data analysis. In the presence of LD between the two blocks, TH takes into account the correlation between the two haplotype blocks and has a lower type I error and higher power than TG. Besides, the feasibility of the methods is shown by sample-size calculation.     

Detailed four-way comparative mapping and gene order analysis of the canine ctvm locus reveals evolutionary chromosome rearrangements

Canine tricuspid valve malformation (CTVM) maps to canine chromosome 9 (CFA9), in a region syntenic with gene-dense human chromosome 17q. To define synteny blocks, we analyzed 148 markers on CFA9 using radiation hybrid mapping and established a four-way comparative map for human, mouse, rat, and dog. We identified a large number of rearrangements, allowing us to reconstruct the evolutionary history of individual synteny blocks and large chromosomal segments. A most parsimonious rearrangement scenario for all four species reveals that human chromosome 17q differs from CFA9 and the syntenic rodent chromosomes through two macroreversals of 9.2 and 23 Mb. Compared to a recovered ancestral gene order, CFA9 has undergone 11 reversals of <3 Mb and 2 reversals of >3 Mb. Interspecies reuse of breakpoints for micro- and macrorearrangements was observed. Gene order and content of the ctvm interval are best extrapolated from murine data, showing that multispecies genome rearrangement scenarios contribute to identifying gene content in canine mapping studies.     

The ABC's of comparative genomics in the Brassicaceae: building blocks of crucifer genomes

In this review we summarize recent advances in our understanding of phylogenetics, polyploidization and comparative genomics in the family Brassicaceae. These findings pave the way for a unified comparative genomic framework. We integrate several of these findings into a simple system of 24 conserved chromosomal blocks (labeled A-X). The naming, order, orientation and color-coding of these blocks are based on their positions in a proposed ancestral karyotype (n=8), rather than by their position in the reduced genome of Arabidopsis thaliana (n=5). We show how these crucifer building blocks can be rearranged to model the genome structures of A. thaliana, Arabidopsis lyrata, Capsella rubella and Brassica rapa. A framework for comparison between species is timely because several crucifer genome-sequencing projects are underway.     

Precise detection of rearrangement breakpoints in mammalian chromosomes

Background  

Genomes undergo large structural changes that alter their organisation. The chromosomal regions affected by these rearrangements are called breakpoints, while those which have not been rearranged are called synteny blocks. We developed a method to precisely delimit rearrangement breakpoints on a genome by comparison with the genome of a related species. Contrary to current methods which search for synteny blocks and simply return what remains in the genome as breakpoints, we propose to go further and to investigate the breakpoints themselves in order to refine them.     

Block alignment: New representation and comparison method to study evolution of genomes

Genomes are not random sequences because natural selection has injected information in biological sequences for billions of years. Inspired by this idea, we developed a simple method to compare genomes considering nucleotide counts in subsequences (blocks) instead of their exact sequences.We introduce the Block Alignment method for comparing two genomes and based on this comparison method, define a similarity score and a distance. The presented model ignores nucleotide order in the sequence. On the other hand, in this block comparison method, due to exclusion of point mutations and small size variations, there is no need for high coverage sequencing which is responsible for the high costs of data production and storage; moreover, the sequence comparisons could be performed with higher speed.Phylogenetic trees of two sets of bacterial genomes were constructed and the results were in full agreement with their already constructed phylogenetic trees. Furthermore, a weighted and directed similarity network of each set of bacterial genomes was inferred ab initio by this model. Remarkably, the communities of these networks are in agreement with the clades of the corresponding phylogenetic trees which means these similarity networks also contain phylogenetic information about the genomes. Moreover, the block comparison method was used to distinguish rob(15;21)c-associated iAMP21 and sporadic iAMP21 rearrangements in subgroups of chromosome 21 in acute lymphoblastic leukemia. Our results show a meaningful difference between the number of contigs that mapped to chromosomes 15 and 21 in these cases. Furthermore, the presented block alignment model can select the candidate blocks to perform more accurate analysis and it is capable to find conserved blocks on a set of genomes.     

Screening synteny blocks in pairwise genome comparisons through integer programming

Background  

It is difficult to accurately interpret chromosomal correspondences such as true orthology and paralogy due to significant divergence of genomes from a common ancestor. Analyses are particularly problematic among lineages that have repeatedly experienced whole genome duplication (WGD) events. To compare multiple "subgenomes" derived from genome duplications, we need to relax the traditional requirements of "one-to-one" syntenic matchings of genomic regions in order to reflect "one-to-many" or more generally "many-to-many" matchings. However this relaxation may result in the identification of synteny blocks that are derived from ancient shared WGDs that are not of interest. For many downstream analyses, we need to eliminate weak, low scoring alignments from pairwise genome comparisons. Our goal is to objectively select subset of synteny blocks whose total scores are maximized while respecting the duplication history of the genomes in comparison. We call this "quota-based" screening of synteny blocks in order to appropriately fill a quota of syntenic relationships within one genome or between two genomes having WGD events.     

The relative extension of alginates having different chemical composition

From light-scattering and viscosity experiments, it was found that the relative extension of the three types of “blocks” in alginate increased in the order “MG-blocks” <“MM-blocks”<“GG-blocks”, both in 0.1M aqueous sodium chloride and in the unperturbed state. From a comparison with calculated free-rotation dimensions, it was concluded that this was due to a difference in the hindrance to rotation around the glycosidic linkage in the different blocks. Calculations by statistical mechanics, using Kitaygorodsky potential functions for the non-bonded interaction between atomic groups in adjacent dimers, yielded unperturbed dimensions which were in agreement with the above order, only when the L-guluronic acid residue was assumed to adopt the 1C (¹C₄) conformation.     

Temporal threshold and response bias in the discrimination of empty intervals by cats

Cat's differential duration threshold was investigated by the method of limits in a schedule of discrimination of empty durations. The standard stimulus was 4 sec long throughout the experiment. The comparison stimulus was reduced from 10 to 5 sec by 1 sec steps in successive blocks of 5 sessions. Standard and comparison stimuli, delimited by 50 msec auditory signals, were equiprobably distributed, in a random sequential order of presentation in each trial. After a 2 sec delay, an auditory signal indicated that reinforcement was available upon a response on one of two levers. Weber fractions around .25 were obtained. Strong response bias developed in most cats. Some consequences of the inhibition of responding induced by the procedure were considered.     

DLMC-Net: Deeper lightweight multi-class classification model for plant leaf disease detection

Plant-leaf disease detection is one of the key problems of smart agriculture which has a significant impact on the global economy. To mitigate this, intelligent agricultural solutions are evolving that aid farmer to take preventive measures for improving crop production. With the advancement of deep learning, many convolutional neural network models have blazed their way to the identification of plant-leaf diseases. However, these models are limited to the detection of specific crops only. Therefore, this paper presents a new deeper lightweight convolutional neural network architecture (DLMC-Net) to perform plant leaf disease detection across multiple crops for real-time agricultural applications. In the proposed model, a sequence of collective blocks is introduced along with the passage layer to extract deep features. These benefits in feature propagation and feature reuse, which results in handling the vanishing gradient problem. Moreover, point-wise and separable convolution blocks are employed to reduce the number of trainable parameters. The efficacy of the proposed DLMC-Net model is validated across four publicly available datasets, namely citrus, cucumber, grapes, and tomato. Experimental results of the proposed model are compared against seven state-of-the-art models on eight parameters, namely accuracy, error, precision, recall, sensitivity, specificity, F1-score, and Matthews correlation coefficient. Experiments demonstrate that the proposed model has surpassed all the considered models, even under complex background conditions, with an accuracy of 93.56%, 92.34%, 99.50%, and 96.56% on citrus, cucumber, grapes, and tomato, respectively. Moreover, the proposed DLMC-Net requires only 6.4 million trainable parameters, which is the second best among the compared models. Therefore, it can be asserted that the proposed model is a viable alternative to perform plant leaf disease detection across multiple crops.     

Product label identification with OCR for model-specific reuse,repair, and recycling: A case study for washing machines

In this study, a procedure to automatically identify the product model by evaluating an image of the label is presented. First, object character recognition (OCR) extracts text from the product label. Second, to identify the product model, the extracted text is compared with unique model references in a database, giving access to other model-specific information. For this comparison, a novel variation of the partial ratio matching algorithm was developed. The product-model identification procedure is integrated into an interactive web application, which allows for model identification to be performed during preparation for reuse, repair, and recycling: The SmartRe application. Three datasets consisting of 466, 422, and 771 images of washing machine product labels were gathered in collaboration with a (1) professional repair company for consumer devices, (2) a nonprofit repair and reuse center that resells devices in second-hand stores, and (3) a large recycling company. Results demonstrate that 96%, 91%, and 40% of the product models were correctly read from the product label with OCR, respectively. Of these recognized models, 51%, 88%, and 76% were successfully identified with the SmartRe application by comparing the extracted text with the model database. Further analysis also demonstrated that 72% of the washing machine models identified at the nonprofit repair and reuse center were also found at the recycling facility and that 12% of these models are predicted to be less than 10-years-old. This highlights the potential of the SmartRe application to assist in product triage for reuse at recycling centers.     

Comparative analysis of human and bovine papillomaviruses

A method is presented for the analysis and comparison of nucleic acid and protein sequences utilizing all identity blocks (the term "identity block" refers to a set of consecutive matches between two sequences) above a prescribed length. Moreover, such identity blocks are determined for various groupings of amino acids according to chemical, functional, charge, and hydrophobic classifications. Alignment maps based on these classifications and containing all statistically significant identity blocks between two or more sequences are constructed. New theoretical results for determining the expected length of the longest identity block between sequences are also presented and are used, along with permutation procedures, to ascertain the significance of sequence identity blocks. As an example of the type of information that can be obtained, comparison has been made of the complete DNA sequences and the E1, E2, L1, and L2 genes of human and bovine papillomaviruses based on the classification schemes described above.     

Supramolecular gene delivery vectors showing enhanced transgene expression and good biocompatibility

Soluble supramolecular inclusion complexes were formed by threading alpha-cyclodextrin (alpha-CD) molecules over poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone) (PCL) chains of ternary block copolymers of PEG, PCL and polyethylenimine (PEI). Characteristic shifts of PCL absorptions in FTIR, (1)H NMR and UV spectra strongly suggest that alpha-CD is threaded over PEG and PCL blocks. Due to the reduced hydrophobic interaction between PCL blocks, the resulting supramolecular complexes displayed a dramatically increased solubility, in comparison with the ternary block copolymers. Their ability to complex DNA was almost as efficient as that of branched PEI 25 kDa, as shown in the ethidium bromide fluorescence quenching experiments. Resulting DNA polyplexes displayed a size of around 200 nm and a neutral surface charge. Microscopy studies in 3T3 fibroblasts revealed an efficient cellular uptake. Transfection efficiencies of inclusion complexes were in the same order of magnitude as PEI. In contrast to PEI a 100x lower toxicity was observed by MTT-assay, allowing the administration of nitrogen-to-phosphate ratios of up to 20. These new gene delivery systems merit further characterization under in vivo conditions.     

A virtual environment for learning to view during aerial movements

Training the gymnasts to view the landing area when learning aerial skills may lead to more consistent landings but can be problematic and potentially dangerous. A virtual environment allowing gymnasts to get introduced to viewing techniques safely is presented. The system is based on existing simulation models and visualisation software, and is implemented using client-server technology to allow reuse with new simulation models in the future.     

Alignment-free comparison of genome sequences by a new numerical characterization

In order to compare different genome sequences, an alignment-free method has proposed. First, we presented a new graphical representation of DNA sequences without degeneracy, which is conducive to intuitive comparison of sequences. Then, a new numerical characterization based on the representation was introduced to quantitatively depict the intrinsic nature of genome sequences, and considered as a 10-dimensional vector in the mathematical space. Alignment-free comparison of sequences was performed by computing the distances between vectors of the corresponding numerical characterizations, which define the evolutionary relationship. Two data sets of DNA sequences were constructed to assess the performance on sequence comparison. The results illustrate well validity of the method. The new numerical characterization provides a powerful tool for genome comparison.     

Bioresistance of poplar wood compressed by combined hydro-thermo-mechanical wood modification (CHTM): Soft rot and brown-rot

This work studied fungal bioresistance of combined hydro-thermo-mechanically modified (CHTM) poplar wood. The CHTM technique, introduced by Mohebby et al. (2009), is a combination of two wood modification techniques-hydrothermal wood modification and densification of wood. Blocks of poplar wood were initially treated hydrothermally at temperatures of 120, 150, and 180 °C for holding times of 0, 30, and 90 min. Afterwards, the treated blocks were compressed by a hot press (160 and 180 °C) for 20 min with a compression set of 60%. After the CHTM-treated blocks were dried, small specimens were cut for soft-rot and brown-rot decay tests according to ENV 807 and EN 113. Mass losses as well as metabolic moisture contents were determined in the decayed samples. Results revealed that the combination of wood modification techniques showed fungal suppression. It was also found that the hydrothermal treatment step could significantly reduce fungal attack in comparison with densification. Reduction of the mass losses was associated with the hydrothermal treatment temperature. Also, the level of metabolic moisture content was correlated with the mass losses for both fungi. Any reduction of the mass loss decreased the moisture content in the wood.     

A virtual environment for learning to view during aerial movements

Training the gymnasts to view the landing area when learning aerial skills may lead to more consistent landings but can be problematic and potentially dangerous. A virtual environment allowing gymnasts to get introduced to viewing techniques safely is presented. The system is based on existing simulation models and visualisation software, and is implemented using client–server technology to allow reuse with new simulation models in the future.