共查询到20条相似文献,搜索用时 390 毫秒
1.
Luis Sanchez-Pulido Laurent Perez Steffen Kuhn Isabelle Vernos Miguel A. Andrade-Navarro 《BMC structural biology》2016,16(1):17
Background
TPX2 (Targeting Protein for Xklp2) is essential for spindle assembly, activation of the mitotic kinase Aurora A and for triggering microtubule nucleation. Homologs of TPX2 in Chordata and plants were previously identified. Currently, proteins of the TPX2 family have little structural information and only small parts are covered by defined protein domains.Methods
We have used computational sequence analyses and structural predictions of proteins of the TPX2 family, supported with Circular Dichroism (CD) measurements.Results
Here, we report our finding that the C-terminal domain of TPX2, which is responsible of its microtubule nucleation capacity and is conserved in all members of the family, is actually formed by tandem repeats, covering well above 2/3 of the protein. We propose that this region forms a flexible solenoid involved in protein-protein interactions. Structural prediction and molecular modeling, combined with Circular Dichroism (CD) measurements reveal a predominant alpha-helical content. Furthermore, we identify full length homologs in fungi and shorter homologs with a different domain organization in diptera (including a paralogous expansion in Drosophila).Conclusions
Our results, represent the first computational and biophysical analysis of the TPX2 proteins family and help understand the structure and evolution of this conserved protein family to direct future structural studies.2.
Nicholas J. Bond Albert Koulman Julian L. Griffin Zoe Hall 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):128
Introduction
Mass spectrometry imaging (MSI) experiments result in complex multi-dimensional datasets, which require specialist data analysis tools.Objectives
We have developed massPix—an R package for analysing and interpreting data from MSI of lipids in tissue.Methods
massPix produces single ion images, performs multivariate statistics and provides putative lipid annotations based on accurate mass matching against generated lipid libraries.Results
Classification of tissue regions with high spectral similarly can be carried out by principal components analysis (PCA) or k-means clustering.Conclusion
massPix is an open-source tool for the analysis and statistical interpretation of MSI data, and is particularly useful for lipidomics applications.3.
Daria V. Dibrova Kirill A. Konovalov Vadim V. Perekhvatov Konstantin V. Skulachev Armen Y. Mulkidjanian 《Biology direct》2017,12(1):29
Background
The Clusters of Orthologous Groups (COGs) of proteins systematize evolutionary related proteins into specific groups with similar functions. However, the available databases do not provide means to assess the extent of similarity between the COGs.Aim
We intended to provide a method for identification and visualization of evolutionary relationships between the COGs, as well as a respective web server.Results
Here we introduce the COGcollator, a web tool for identification of evolutionarily related COGs and their further analysis. We demonstrate the utility of this tool by identifying the COGs that contain distant homologs of (i) the catalytic subunit of bacterial rotary membrane ATP synthases and (ii) the DNA/RNA helicases of the superfamily 1.Reviewers
This article was reviewed by Drs. Igor N. Berezovsky, Igor Zhulin and Yuri Wolf.4.
Background
Human cancers are complex ecosystems composed of cells with distinct molecular signatures. Such intratumoral heterogeneity poses a major challenge to cancer diagnosis and treatment. Recent advancements of single-cell techniques such as scRNA-seq have brought unprecedented insights into cellular heterogeneity. Subsequently, a challenging computational problem is to cluster high dimensional noisy datasets with substantially fewer cells than the number of genes.Methods
In this paper, we introduced a consensus clustering framework conCluster, for cancer subtype identification from single-cell RNA-seq data. Using an ensemble strategy, conCluster fuses multiple basic partitions to consensus clusters.Results
Applied to real cancer scRNA-seq datasets, conCluster can more accurately detect cancer subtypes than the widely used scRNA-seq clustering methods. Further, we conducted co-expression network analysis for the identified melanoma subtypes.Conclusions
Our analysis demonstrates that these subtypes exhibit distinct gene co-expression networks and significant gene sets with different functional enrichment.5.
Background
Most phylogenetic studies using molecular data treat gaps in multiple sequence alignments as missing data or even completely exclude alignment columns that contain gaps.Results
Here we show that gap patterns in large-scale, genome-wide alignments are themselves phylogenetically informative and can be used to infer reliable phylogenies provided the gap data are properly filtered to reduce noise introduced by the alignment method. We introduce here the notion of split-inducing indels (splids) that define an approximate bipartition of the taxon set. We show both in simulated data and in case studies on real-life data that splids can be efficiently extracted from phylogenomic data sets.Conclusions
Suitably processed gap patterns extracted from genome-wide alignment provide a surprisingly clear phylogenetic signal and an allow the inference of accurate phylogenetic trees.6.
Conrad Helm Patrick Beckers Thomas Bartolomaeus Stephan H. Drukewitz Ioannis Kourtesis Anne Weigert Günter Purschke Katrine Worsaae Torsten H. Struck Christoph Bleidorn 《Frontiers in zoology》2018,15(1):36
Background
A median, segmented, annelid nerve cord has repeatedly been compared to the arthropod and vertebrate nerve cords and became the most used textbook representation of the annelid nervous system. Recent phylogenomic analyses, however, challenge the hypothesis that a subepidermal rope-ladder-like ventral nerve cord (VNC) composed of a paired serial chain of ganglia and somata-free connectives represents either a plesiomorphic or a typical condition in annelids.Results
Using a comparative approach by combining phylogenomic analyses with morphological methods (immunohistochemistry and CLSM, histology and TEM), we compiled a comprehensive dataset to reconstruct the evolution of the annelid VNC. Our phylogenomic analyses generally support previous topologies. However, the so far hard-to-place Apistobranchidae and Psammodrilidae are now incorporated among the basally branching annelids with high support. Based on this topology we reconstruct an intraepidermal VNC as the ancestral state in Annelida. Thus, a subepidermal ladder-like nerve cord clearly represents a derived condition.Conclusions
Based on the presented data, a ladder-like appearance of the ventral nerve cord evolved repeatedly, and independently of the transition from an intraepidermal to a subepidermal cord during annelid evolution. Our investigations thereby propose an alternative set of neuroanatomical characteristics for the last common ancestor of Annelida or perhaps even Spiralia.7.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.8.
Background
For many RNA molecules, secondary structure rather than primary sequence is the evolutionarily conserved feature. No programs have yet been published that allow searching a sequence database for homologs of a single RNA molecule on the basis of secondary structure.Results
We have developed a program, RSEARCH, that takes a single RNA sequence with its secondary structure and utilizes a local alignment algorithm to search a database for homologous RNAs. For this purpose, we have developed a series of base pair and single nucleotide substitution matrices for RNA sequences called RIBOSUM matrices. RSEARCH reports the statistical confidence for each hit as well as the structural alignment of the hit. We show several examples in which RSEARCH outperforms the primary sequence search programs BLAST and SSEARCH. The primary drawback of the program is that it is slow. The C code for RSEARCH is freely available from our lab's website.Conclusion
RSEARCH outperforms primary sequence programs in finding homologs of structured RNA sequences.9.
Rachel A. Spicer Christoph Steinbeck 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):16
Introduction
Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.Objectives
(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.Methods
A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.Results
Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.Conclusion
Further efforts are required to improve data sharing in metabolomics.10.
Background
In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.Methods
The physical basis of these intuitive maps is clarified by means of analytically solvable problems.Results
Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.Conclusion
Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.11.
Background
Existing clustering approaches for microarray data do not adequately differentiate between subsets of co-expressed genes. We devised a novel approach that integrates expression and sequence data in order to generate functionally coherent and biologically meaningful subclusters of genes. Specifically, the approach clusters co-expressed genes on the basis of similar content and distributions of predicted statistically significant sequence motifs in their upstream regions.Results
We applied our method to several sets of co-expressed genes and were able to define subsets with enrichment in particular biological processes and specific upstream regulatory motifs.Conclusions
These results show the potential of our technique for functional prediction and regulatory motif identification from microarray data.12.
Jonathan M. Wagner Sum Chan Timothy J. Evans Sara Kahng Jennifer Kim Mark A. Arbing David Eisenberg Konstantin V. Korotkov 《BMC structural biology》2016,16(1):5
Background
The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system.Results
This study characterizes the structures of the soluble domains of two conserved core ESX-1 components – EccB1 and EccD1. The periplasmic domain of EccB1 consists of 4 repeat domains and a central domain, which together form a quasi 2-fold symmetrical structure. The repeat domains of EccB1 are structurally similar to a known peptidoglycan binding protein suggesting a role in anchoring the ESX-1 system within the periplasmic space. The cytoplasmic domain of EccD1has a ubiquitin-like fold and forms a dimer with a negatively charged groove.Conclusions
These structures represent a major step towards resolving the molecular architecture of the entire ESX-1 assembly and may contribute to ESX-1 targeted tuberculosis intervention strategies.13.
Introduction
Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.Objectives
Assessment of the quality of raw data processing in untargeted metabolomics.Methods
Five published untargeted metabolomics studies, were reanalyzed.Results
Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.Conclusion
Incomplete raw data processing shows unexplored potential of current and legacy data.14.
Renato de Souza Pinto Lemgruber Kaspar Valgepea Mark P. Hodson Ryan Tappel Sean D. Simpson Michael Köpke Lars K. Nielsen Esteban Marcellin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):35
Introduction
Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.Objective
To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.Methods
Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.Results
Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.Conclusion
Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.15.
Pathomwat Wongrattanakamon Vannajan Sanghiran Lee Piyarat Nimmanpipug Supat Jiranusornkul 《生物学前沿》2016,11(5):391-395
Background
P-glycoprotein (P-gp) is a 170-kDa membrane protein. It provides a barrier function and help to excrete toxins from the body as a transporter. Some bioflavonoids have been shown to block P-gp activity.Objective
To evaluate the important amino acid residues within nucleotide binding domain 1 (NBD1) of P-gp that play a key role in molecular interactions with flavonoids using structure-based pharmacophore model.Methods
In the molecular docking with NBD1 models, a putative binding site of flavonoids was proposed and compared with the site for ATP. The binding modes for ligands were achieved using LigandScout to generate the P-gp–flavonoid pharmacophore models.Results
The binding pocket for flavonoids was investigated and found these inhibitors compete with the ATP for binding site in NBD1 including the NBD1 amino acid residues identified by the in silico techniques to be involved in the hydrogen bonding and van der Waals (hydrophobic) interactions with flavonoids.Conclusion
These flavonoids occupy with the same binding site of ATP in NBD1 proffering that they may act as an ATP competitive inhibitor.16.
Ferran Casbas Pinto Srinivarao Ravipati David A. Barrett T. Charles Hodgman 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):81
Introduction
It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.Objectives
This work simplifies this process.Methods
A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.Results
The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.Conclusion
This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.17.
18.
Jamie V. de Seymour Stephanie Tu Xiaoling He Hua Zhang Ting-Li Han Philip N. Baker Karolina Sulek 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):79
Introduction
Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.Objective
Investigate the maternal hair metabolome for predictive biomarkers of ICP.Methods
The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.Results
Of 105 metabolites detected in hair, none were significantly associated with ICP.Conclusion
Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.19.
Sonia Liggi Christine Hinz Zoe Hall Maria Laura Santoru Simone Poddighe John Fjeldsted Luigi Atzori Julian L. Griffin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):52
Introduction
Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.Objectives
Merge in the same platform the steps required for metabolomics data processing.Methods
KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.Results
The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.Conclusion
KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.20.
Thijs Welle Anna T. Hoekstra Ineke A. J. J. M. Daemen Celia R. Berkers Matheus O. Costa 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):83