Alignment Program Research Articles

Telescope alignment based on the sharpness function of under-sampled images

The precise alignment of a high-performance telescope is a key factor to ensure the imaging quality. However, for telescopes with a wide field of view, the images are sometimes under-sampled. To study the effects of under-sampled images on the precision of telescope alignment, numerical simulations are implemented with the stochastic parallel gradient descent algorithm. The results show that the alignment program can converge stably and quickly. However, with the reduction of the full width at half-maximum of images, the relative residual errors increase from 9.5% to 19.5%, and the wavefront errors raise from 0.0972λ to 0.1074λ, indicating that the accuracy of the alignment decreases.

Motif-Aware PRALINE: Improving the alignment of motif regions.

Protein or DNA motifs are sequence regions which possess biological importance. These regions are often highly conserved among homologous sequences. The generation of multiple sequence alignments (MSAs) with a correct alignment of the conserved sequence motifs is still difficult to achieve, due to the fact that the contribution of these typically short fragments is overshadowed by the rest of the sequence. Here we extended the PRALINE multiple sequence alignment program with a novel motif-aware MSA algorithm in order to address this shortcoming. This method can incorporate explicit information about the presence of externally provided sequence motifs, which is then used in the dynamic programming step by boosting the amino acid substitution matrix towards the motif. The strength of the boost is controlled by a parameter, α. Using a benchmark set of alignments we confirm that a good compromise can be found that improves the matching of motif regions while not significantly reducing the overall alignment quality. By estimating α on an unrelated set of reference alignments we find there is indeed a strong conservation signal for motifs. A number of typical but difficult MSA use cases are explored to exemplify the problems in correctly aligning functional sequence motifs and how the motif-aware alignment method can be employed to alleviate these problems.

Considerations for Optimization of High-Throughput Sequencing Bioinformatics Pipelines for Virus Detection.

High-throughput sequencing (HTS) has demonstrated capabilities for broad virus detection based upon discovery of known and novel viruses in a variety of samples, including clinical, environmental, and biological. An important goal for HTS applications in biologics is to establish parameter settings that can afford adequate sensitivity at an acceptable computational cost (computation time, computer memory, storage, expense or/and efficiency), at critical steps in the bioinformatics pipeline, including initial data quality assessment, trimming/cleaning, and assembly (to reduce data volume and increase likelihood of appropriate sequence identification). Additionally, the quality and reliability of the results depend on the availability of a complete and curated viral database for obtaining accurate results; selection of sequence alignment programs and their configuration, that retains specificity for broad virus detection with reduced false-positive signals; removal of host sequences without loss of endogenous viral sequences of interest; and use of a meaningful reporting format, which can retain critical information of the analysis for presentation of readily interpretable data and actionable results. Furthermore, after alignment, both automated and manual evaluation may be needed to verify the results and help assign a potential risk level to residual, unmapped reads. We hope that the collective considerations discussed in this paper aid toward optimization of data analysis pipelines for virus detection by HTS.

BWTaligner: a genome short-read aligner

The development of next-generation sequencing tech-nologies has helped sequence large genomes easily, producing a huge number of short-reads - small frag-ments of DNA. Despite the existence of many developed alignment tools, mapping short-read datasets to the reference genome, a crucial step of genome analysis, still remains a challenge. In this study, we develop a short-read alignment program, BWTaligner, based on the Burrows-Wheeler transform compression - exact and inexact matching. We tested it on the paired-end read data simulated from chromosome 9 of the rice genome to compare the alignment and single-nucleo-tide polymorphism (SNP) calling between our aligner and BWA - the preferred alignment program. The re-sults showed that the BWA delivers higher recall and F-score, while BWTaligner has better precision in high coveragedepth.

NONLINEAR FM INDEX APPLICATION FOR ALIGNMENT OF SHORT DNA SEQUENCES USING RE-PARAMETRIZATION OF ALGORITHMS

An innovative reconfiguration application is proposed to re-calculate the parameters of the Ferragina and Manzini exact search algorithm (or FM indexes), using a modular and efficient hardware implementation to accelerate alignment programs of short DNA sequence reads. Although these programs use multi-core execution strategies or multiple computers, they have become slow considering the very high speed at which the new massively parallel sequencing machines produce the reads to be aligned. Consequently, a search for different ways to accelerate the alignment is crucial. The proposed design runs with software functions in a hybrid system, and has the ability to align millions of reads to reference as large as the human genome. Tests on the M505k325t card show that a single alignment core can accelerate the computation by a factor close to [Formula: see text] in relation to BWA. Due to the minor consumption of area and power, multiple alignment cores can fill the Field Programmable Gate Array (FPGA) by multiplying the computation speed. With a multiple-core implementation, the processing speed of the design outperforms applications that are accelerated by GPUs and competes with similar FPGA proposals whose cost is much higher.

Minimap2: pairwise alignment for nucleotide sequences.

Recent advances in sequencing technologies promise ultra-long reads of ∼100 kb in average, full-length mRNA or cDNA reads in high throughput and genomic contigs over 100 Mb in length. Existing alignment programs are unable or inefficient to process such data at scale, which presses for the development of new alignment algorithms. Minimap2 is a general-purpose alignment program to map DNA or long mRNA sequences against a large reference database. It works with accurate short reads of ≥100 bp in length, ≥1 kb genomic reads at error rate ∼15%, full-length noisy Direct RNA or cDNA reads and assembly contigs or closely related full chromosomes of hundreds of megabases in length. Minimap2 does split-read alignment, employs concave gap cost for long insertions and deletions and introduces new heuristics to reduce spurious alignments. It is 3-4 times as fast as mainstream short-read mappers at comparable accuracy, and is ≥30 times faster than long-read genomic or cDNA mappers at higher accuracy, surpassing most aligners specialized in one type of alignment. https://github.com/lh3/minimap2. Supplementary data are available at Bioinformatics online.

MICAN-SQ: a sequential protein structure alignment program that is applicable to monomers and all types of oligomers.

Protein structure alignment is a significant tool to understand evolutionary processes and physicochemical properties of proteins. Important targets of structure alignment are not only monomeric but also oligomeric proteins that sometimes include domain swapping or fusions. Although various protein structural alignment programs have been developed, no method is applicable to any protein pair regardless of the number of chain components and oligomeric states with retaining sequential restrictions: structurally equivalent regions must be aligned in the same order along protein sequences. In this paper, we introduced a new sequential protein structural alignment algorithm MICAN-SQ, which is applicable to protein structures in all oligomeric states. In particular, MICAN-SQ allows the complicated structural alignments of proteins with domain swapping or fusion regions. To validate MICAN-SQ, alignment accuracies were evaluated using curated alignments of monomers and examples of domain swapping, and compared with those of pre-existing protein structural alignment programs. The results of this study show that MICAN-SQ has superior accuracy and robustness in comparison with previous programs and offers limited computational times. We also demonstrate that MICAN-SQ correctly aligns very large complexes and fused proteins. The present computations warrant the consideration of MICAN-SQ for studies of evolutionary and physicochemical properties of monomeric structures and all oligomer types. The MICAN program was implemented in C. The source code and executable file can be freely downloaded from http://www.tbp.cse.nagoya-u.ac.jp/MICAN/. Supplementary data are available at Bioinformatics online.

A family of long intergenic non-coding RNA genes in human chromosomal region 22q11.2 carry a DNA translocation breakpoint/AT-rich sequence.

FAM230C, a long intergenic non-coding RNA (lincRNA) gene in human chromosome 13 (chr13) is a member of lincRNA genes termed family with sequence similarity 230. An analysis using bioinformatics search tools and alignment programs was undertaken to determine properties of FAM230C and its related genes. Results reveal that the DNA translocation element, the Translocation Breakpoint Type A (TBTA) sequence, which consists of satellite DNA, Alu elements, and AT-rich sequences is embedded in the FAM230C gene. Eight lincRNA genes related to FAM230C also carry the TBTA sequences. These genes were formed from a large segment of the 3’ half of the FAM230C sequence duplicated in chr22, and are specifically in regions of low copy repeats (LCR22)s, in or close to the 22q.11.2 region. 22q11.2 is a chromosomal segment that undergoes a high rate of DNA translocation and is prone to genetic deletions. FAM230C-related genes present in other chromosomes do not carry the TBTA motif and were formed from the 5’ half region of the FAM230C sequence. These findings identify a high specificity in lincRNA gene formation by gene sequence duplication in different chromosomes.

Effects of dialysate to serum sodium (Na+) alignment in chronic hemodialysis (HD) patients: retrospective cohort study from a quality improvement project

BackgroundEvidence indicates favorable effects of dialysate (DNa+) to serum sodium concentration (SNa+) alignment, however, results from larger sample populations are needed. For this reason, we conducted a retrospective propensity score-matched cohort study from a quality improvement project to investigate the effects of alignment on population of maintenance hemodialysis patients.MethodsAt 4 participating hemodialysis (HD) clinics, patients with SNa+ lower than the standard DNa+ of 137 mEq/L who received HD with DNa+ aligned to the average of the last 4 SNa+ measurements were evaluated (clinicaltrials.gov #NCT01825590). In this retrospective data analysis, an intention-to-treat (primary) and an as-treated “intervention” (secondary) cohort were created. “Aligned” patients from both cohorts (N = 163 for the primary and N = 137 for the secondary) were then propensity-score matched in a 1:1 fashion to “unaligned” patients from the Renal Research Institute database. The propensity score was generated based on age, gender, white race, Hispanic ethnicity, absence or presence of diabetes, hemodialysis vintage, interdialytic weight gain (IDWG; as a percentage of postdialysis body weight), catheter as primary dialysis access, predialysis systolic blood pressure, serum sodium concentration, hospitalization count during baseline. T-Test was employed for group comparisons of changes to the primary (volume-related and hemodynamic parameters) and tertiary outcomes. All-cause and fluid overload-related hospitalization admission rates were compared using Wilcoxon Rank Sum test and Cox regression analysis for repeated events.ResultsIn the primary analysis, aligned and unaligned subjects showed comparable demographics at baseline. Treatment effects were significant for IDWG [−0.12 (95% CI −0.24 to 0) L] and showed decreasing non-significant trends for pre-dialysis hemodynamic parameters. Count comparison and Cox regression analysis showed no clear advantage of alignment in terms of all-cause and fluid overload-related hospitalization.ConclusionsResults from the largest sodium alignment program to date suggest positive treatment effects on volume-related and hemodynamic parameters, but no clear effect on risk of hospitalization. Well-matched control patients minimized confounding effects. Small effects and lack of significant differences may be explained by a low baseline DNa+ limiting the interventional change.

Metro North GP Alignment Program: Maternity and Gynaecology

Introduction: Perinatal care in the community did not align with care provided in hospital. General Practitioner (GP) knowledge gaps in relation to hospital referral processes, pregnancy care, postnatal care & common gynaecological conditions were identified. Local resources to support GPs at the point of care did not exist.Practice Change Implemented: Metro North Hospital and Health Service (HHS) Women’s & Children’s Stream and Brisbane North Primary Health Network (PHN) developed an education program for GPs including workshops, resources to support GPs at the point of care, an online refresher course and forums to facilitate communication between consumers, primary care and hospital clinicians.Aims: Enable seamless care delivery between primary care and hospital for women and babiesAlign care provided in the community with care provided in hospitalStrengthen partnerships between primary care and hospital and develop robust clinical pathways for maternity & gynaecologyImprove GP knowledge of referral and care processesTargeted population & stakeholdersWomen and babies in Metro North Brisbane and the GPs who care for them,Metro North HHS & Brisbane North PHNTimeline: Workshops have been delivered regularly since 2014Highlights: Over 400 GPs have completed the program with more than 80% reporting their learning needs were entirely met. GP knowledge improved as measured by pre and post workshop assessment. There was a 25% improvement in GP compliance with plotting foetal growth on standardized growth charts.The quality of referrals improved with more GPs using electronic referral templates. The GP resources are being used to inform localised Health Pathways.Sustainability: This program of education and collaboration is now part of “business as usual”.Transferability: This program is transferable to other health service districts and the model is transferable to other specialties.Conclusions: The Program delivered education and strengthened partnerships between facilities & services within and external to Metro North HHS. Where service and process gaps were identified, the partnerships developed enabled system improvements.Discussions: There is strength in an interdisciplinary approach to program development and delivery. Acknowledgement and support of the different priorities of each population and each facility allows workshop content to be adapted to suit.Lessons learned: Focus on what is best for women and babies. Executive support is paramount.

The Paediatric Optometry Alignment Program - Integrated care between hospital based paediatric ophthalmology and community based optometry

The Paediatric Optometry Alignment Program (POAP) was developed in response to uncontrollable demand for paediatric ophthalmology services, and consequent an excessive outpatient waiting list in Queensland’s only dedicated children’s hospital (Lady Cilento Children’s Hospital, LCCH). The project development objective was to initiate discharge pathways for children whose eye conditions could be managed by primary care optometrists. The geographic coverage of primary care optometrists in rural and urban locations offered the potential to provide patients with local care, addressing issues of transport, cost and access that are known barriers to eye care service delivery. Stakeholders include the children and families treated by LCCH ophthalmology, Children’s Health Queensland, paediatric ophthalmologists and community based optometrists. Project development objectives include : To increase knowledge and skills of the primary care optometry workforce in paediatric eye care, thus building capacity for primary care delivery in the community. To build relationships and clinical communication pathways between primary care optometry and the specialist ophthalmology department. To reduce waiting times for those patients who require secondary and tertiary care of LCCH Ophthalmology Outpatient Department. The program has developed an integrated care model for children with specific eye conditions; provided continuing education in paediatric eye care to the current optometry workforce; and promoted a collaborative relationship between specialty ophthalmologists and primary care optometrists. A network of nearly 100 community-based primary care optometrists from across Queensland have completed specific education in paediatric eye care and agreed to collaborative care protocols. Over 250 children have been discharged to the network for their future eye care. Qualitative assessment of practitioner attitude and understanding of integrated care delivery was determined at the outset of the program by focus group interviews with participating optometrists and ophthalmology department representatives. Education activity then included face-to-face workshops presented in Brisbane and in Cairns, development of an on-line portal for access to further education materials, quarterly short-topics meet ups hosted at LCCH and by video-conference, and mentoring the development of a paediatric optometry Journal Club. Clinical staff of LCCH ophthalmology department following established protocols identified children eligible for discharge to an optometrist for monitoring of their stable eye condition. The discharge process commenced from June 2016, with follow-up monitoring appointments expected with optometrists from June 2017. Follow-up focus group interviews and clinical reports back from the optometrists will be used as tracking indicators. Challenges : Variability in clinical management philosophy was identified within the interested optometry applicants. Determination of common ground in diagnosis and management of the predominant eye conditions that form the basis of the discharge programme was required, with agreement on evidence based management protocols required for program success. Successes : Since commencement of the program, the diversity of patient groups to be referred to community-based optometry has expanded. Transferability : Integrated care between local optometrists and hospital-based ophthalmologists offers opportunity for provision of local care for beneficial patient outcomes and provides a solution to reducing hospital demand. Collaboratively developed standards for safe care are required, in addition to continued nurturing of partnerships and inter-professional trust.

Parallelization of MAFFT for large-scale multiple sequence alignments.

SummaryWe report an update for the MAFFT multiple sequence alignment program to enable parallel calculation of large numbers of sequences. The G-INS-1 option of MAFFT was recently reported to have higher accuracy than other methods for large data, but this method has been impractical for most large-scale analyses, due to the requirement of large computational resources. We introduce a scalable variant, G-large-INS-1, which has equivalent accuracy to G-INS-1 and is applicable to 50 000 or more sequences.Availability and implementationThis feature is available in MAFFT versions 7.355 or later at https://mafft.cbrc.jp/alignment/software/mpi.html.Supplementary information Supplementary data are available at Bioinformatics online.

LS-align: an atom-level, flexible ligand structural alignment algorithm for high-throughput virtual screening.

Sequence-order independent structural comparison, also called structural alignment, of small ligand molecules is often needed for computer-aided virtual drug screening. Although many ligand structure alignment programs are proposed, most of them build the alignments based on rigid-body shape comparison which cannot provide atom-specific alignment information nor allow structural variation; both abilities are critical to efficient high-throughput virtual screening. We propose a novel ligand comparison algorithm, LS-align, to generate fast and accurate atom-level structural alignments of ligand molecules, through an iterative heuristic search of the target function that combines inter-atom distance with mass and chemical bond comparisons. LS-align contains two modules of Rigid-LS-align and Flexi-LS-align, designed for rigid-body and flexible alignments, respectively, where a ligand-size independent, statistics-based scoring function is developed to evaluate the similarity of ligand molecules relative to random ligand pairs. Large-scale benchmark tests are performed on prioritizing chemical ligands of 102 protein targets involving 1 415 871 candidate compounds from the DUD-E (Database of Useful Decoys: Enhanced) database, where LS-align achieves an average enrichment factor (EF) of 22.0 at the 1% cutoff and the AUC score of 0.75, which are significantly higher than other state-of-the-art methods. Detailed data analyses show that the advanced performance is mainly attributed to the design of the target function that combines structural and chemical information to enhance the sensitivity of recognizing subtle difference of ligand molecules and the introduces of structural flexibility that help capture the conformational changes induced by the ligand-receptor binding interactions. These data demonstrate a new avenue to improve the virtual screening efficiency through the development of sensitive ligand structural alignments. http://zhanglab.ccmb.med.umich.edu/LS-align/. Supplementary data are available at Bioinformatics online.

The method of the examination of dangerous structures and rehabilitationof their robustness

There are a variety of methods concerning the examination of dangerous structures and rehabilitation of their robustness. One of the methods is uplifting and alignment of buildings with the use of hydraulic jack. Development of the uplift and alignment program is possible if there is a data, which is to be received both before the beginning of the uplift and during the process of recovery of spatial geometry of the building. The development of the uplift and alignment program automatically controls the speed rate of the hydraulic system. The suggested method enables an accurate control of a vertical reach and provides the minimal overload on deformable footing and structure of the building during its uplift and alignment.

MTM-align: an algorithm for fast and accurate multiple protein structure alignment.

As protein structure is more conserved than sequence during evolution, multiple structure alignment can be more informative than multiple sequence alignment, especially for distantly related proteins. With the rapid increase of the number of protein structures in the Protein Data Bank, it becomes urgent to develop efficient algorithms for multiple structure alignment. A new multiple structure alignment algorithm (mTM-align) was proposed, which is an extension of the highly efficient pairwise structure alignment program TM-align. The algorithm was benchmarked on four widely used datasets, HOMSTRAD, SABmark_sup, SABmark_twi and SISY-multiple, showing that mTM-align consistently outperforms other algorithms. In addition, the comparison with the manually curated alignments in the HOMSTRAD database shows that the automated alignments built by mTM-align are in general more accurate. Therefore, mTM-align may be used as a reliable complement to construct multiple structure alignments for real-world applications. http://yanglab.nankai.edu.cn/mTM-align. zhng@umich.edu or yangjy@nankai.edu.cn. Supplementary data are available at Bioinformatics online.

Association of single nucleotide polymorphisms of PPP1R11 gene with conception rate in Karan Fries bull

Bull fertility is an important component of reproductive efficiency in dairy cattle. PPP1R11 is a potent candidate gene for bull fertility being involved in the pathway of spermatogenesis. Present investigation was carried out in twenty Karan Fries (KF) bull to identify SNPs of PPP1R11 gene and their association with conception rate. Genomic DNA was extracted from frozen semen straws by phenol-chloroform method. Primer pair targeted to exonic II region of PPP1R11 gene was designed using Primer 3.1 software. PCR reactions were carried out in thermal cycler after optimizing. The PCR product was checked on 1.5% horizontal agarose gel electrophoresis to verify the amplification of target region. Samples were sequenced and SNPs were identified using multiple alignment programme with respect to reference sequence and visual inspection of chromatograms. Sequencing results revealed only two SNPs [G28708846A, T28708860C] at exonic II region of PPP1R11 gene in KF bulls. Each bull was genotyped with respect to each of the two identified SNPs. Association of SNP genotype with conception rate was analyzed using least square ANOVA taking genotypes as fixed effect. The result indicated that, only one SNP [T28708860C] had significant (p>0.01) effect on conception rate. The bulls with TT genotype revealed significantly (p>0.01) highest conception rate (53.20±2.96%) followed by bulls with TC (43.12±2.39%) and the lowest in bulls with CC (34.59± 2.28%) genotypes. The results of present finding suggested that association of SNPs with conception rate after validation on large population might be useful in marker assisted selection for selection of bull with high fertility in future.

Confocal depth-resolved fluorescence micro-X-ray absorption spectroscopy for the study of cultural heritage materials: a new mobile endstation at the Beijing Synchrotron Radiation Facility.

A confocal fluorescence endstation for depth-resolved micro-X-ray absorption spectroscopy is described. A polycapillary half-lens defines the incident beam path and a second polycapillary half-lens at 90° defines the probe sample volume. An automatic alignment program based on an evolutionary algorithm is employed to make the alignment procedure efficient. This depth-resolved system was examined on a general X-ray absorption spectroscopy (XAS) beamline at the Beijing Synchrotron Radiation Facility. Sacrificial red glaze (AD 1368-1644) china was studied to show the capability of the instrument. As a mobile endstation to be applied on multiple beamlines, the confocal system can improve the function and flexibility of general XAS beamlines, and extend their capabilities to a wider user community.

A single amino acid in MRGPRX2 necessary for binding and activation by pruritogens

A single amino acid in MRGPRX2 necessary for binding and activation by pruritogens

Flavivirus and Filovirus EvoPrinters: New alignment tools for the comparative analysis of viral evolution.

BackgroundFlavivirus and Filovirus infections are serious epidemic threats to human populations. Multi-genome comparative analysis of these evolving pathogens affords a view of their essential, conserved sequence elements as well as progressive evolutionary changes. While phylogenetic analysis has yielded important insights, the growing number of available genomic sequences makes comparisons between hundreds of viral strains challenging. We report here a new approach for the comparative analysis of these hemorrhagic fever viruses that can superimpose an unlimited number of one-on-one alignments to identify important features within genomes of interest.Methodology/Principal findingWe have adapted EvoPrinter alignment algorithms for the rapid comparative analysis of Flavivirus or Filovirus sequences including Zika and Ebola strains. The user can input a full genome or partial viral sequence and then view either individual comparisons or generate color-coded readouts that superimpose hundreds of one-on-one alignments to identify unique or shared identity SNPs that reveal ancestral relationships between strains. The user can also opt to select a database genome in order to access a library of pre-aligned genomes of either 1,094 Flaviviruses or 460 Filoviruses for rapid comparative analysis with all database entries or a select subset. Using EvoPrinter search and alignment programs, we show the following: 1) superimposing alignment data from many related strains identifies lineage identity SNPs, which enable the assessment of sublineage complexity within viral outbreaks; 2) whole-genome SNP profile screens uncover novel Dengue2 and Zika recombinant strains and their parental lineages; 3) differential SNP profiling identifies host cell A-to-I hyper-editing within Ebola and Marburg viruses, and 4) hundreds of superimposed one-on-one Ebola genome alignments highlight ultra-conserved regulatory sequences, invariant amino acid codons and evolutionarily variable protein-encoding domains within a single genome.Conclusions/SignificanceEvoPrinter allows for the assessment of lineage complexity within Flavivirus or Filovirus outbreaks, identification of recombinant strains, highlights sequences that have undergone host cell A-to-I editing, and identifies unique input and database SNPs within highly conserved sequences. EvoPrinter’s ability to superimpose alignment data from hundreds of strains onto a single genome has allowed us to identify unique Zika virus sublineages that are currently spreading in South, Central and North America, the Caribbean, and in China. This new set of integrated alignment programs should serve as a useful addition to existing tools for the comparative analysis of these viruses.

P060 Drug resistance among women attending antenatal clinics in ghana

IntroductionInitial evidence from resource-limited countries using the WHO HIV drug resistance (HIVDR) threshold survey suggests that transmission of drug-resistance strains is likely to be limited. However, as access to ART...