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1.
D. Jacob C. Deborde M. Lefebvre M. Maucourt A. Moing 《Metabolomics : Official journal of the Metabolomic Society》2017,13(4):36
Introduction
Concerning NMR-based metabolomics, 1D spectra processing often requires an expert eye for disentangling the intertwined peaks.Objectives
The objective of NMRProcFlow is to assist the expert in this task in the best way without requirement of programming skills.Methods
NMRProcFlow was developed to be a graphical and interactive 1D NMR (1H & 13C) spectra processing tool.Results
NMRProcFlow (http://nmrprocflow.org), dedicated to metabolic fingerprinting and targeted metabolomics, covers all spectra processing steps including baseline correction, chemical shift calibration and alignment.Conclusion
Biologists and NMR spectroscopists can easily interact and develop synergies by visualizing the NMR spectra along with their corresponding experimental-factor levels, thus setting a bridge between experimental design and subsequent statistical analyses.2.
Zhongwei Xu Kaimin Xu Shijia Ding Jiao Luo Tingmei Chen Aiguo Zhou Zhenxing Wen Jian Zhang 《Metabolomics : Official journal of the Metabolomic Society》2017,13(6):73
Introduction
Non-traumatic osteonecrosis of the femoral head (NTONFH) is a progressive disease, always leading to hip dysfunction if no early intervention was applied. The difficulty for early diagnosis of NTONFH is due to the slight symptoms at early stages as well as the high cost for screening patients by using magnetic resonance imaging.Objective
The aim was to detect biomarkers of early-stage NTONFH, which was beneficial to the exploration of a cost-effective approach for the early diagnose of the disease.Methods
Metabolomic approaches were employed in this study to detect biomarkers of early-stage NTONFH (22 patients, 23 controls), based on the platform of ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and the uses of multivariate statistic analysis, putative metabolite identification, metabolic pathway analysis and biomarker analysis.Results
In total, 33 serum metabolites were found altered between NTONFH group and control group. In addition, glycerophospholipid metabolism and pyruvate metabolism were highly associated with the disease.Conclusion
The combination of LysoPC (18:3), l-tyrosine and l-leucine proved to have a high diagnostic value for early-stage NTONFH. Our findings may contribute to the protocol for early diagnosis of NTONFH and further elucidate the underlying mechanisms of the disease.3.
Christina Nieuwoudt Samantha J. Jones Angela Brooks-Wilson Jinko Graham 《Source code for biology and medicine》2018,13(1):2
Background
Studies that ascertain families containing multiple relatives affected by disease can be useful for identification of causal, rare variants from next-generation sequencing data.Results
We present the R package SimRVPedigree, which allows researchers to simulate pedigrees ascertained on the basis of multiple, affected relatives. By incorporating the ascertainment process in the simulation, SimRVPedigree allows researchers to better understand the within-family patterns of relationship amongst affected individuals and ages of disease onset.Conclusions
Through simulation, we show that affected members of a family segregating a rare disease variant tend to be more numerous and cluster in relationships more closely than those for sporadic disease. We also show that the family ascertainment process can lead to apparent anticipation in the age of onset. Finally, we use simulation to gain insight into the limit on the proportion of ascertained families segregating a causal variant. SimRVPedigree should be useful to investigators seeking insight into the family-based study design through simulation.4.
Ilse M. Boudewijn Alen Faiz Katrina Steiling Erica van der Wiel Eef D. Telenga Susan J. M. Hoonhorst Nick H. T. ten Hacken Corry-Anke Brandsma Huib A. M. Kerstjens Wim Timens Irene H. Heijink Marnix R. Jonker Harold G. de Bruin J. Sebastiaan Vroegop Henk R. Pasma Wim G. Boersma Pascal Wielders Frank van den Elshout Khaled Mansour Avrum Spira Marc E. Lenburg Victor Guryev Dirkje S. Postma Maarten van den Berge 《Respiratory research》2017,18(1):213
Background
Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium.Methods
Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls.Results
In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate?<?0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA <?0.001).Conclusion
We identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD.Trial registration
ClinicalTrials.gov registration number NCT01351792 (registration date May 10, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 19, 2009), ClinicalTrials.gov registration number NCT00807469 (registration date December 11, 2008).5.
Background
Finding potential drug targets is a crucial step in drug discovery and development. Recently, resources such as the Library of Integrated Network-Based Cellular Signatures (LINCS) L1000 database provide gene expression profiles induced by various chemical and genetic perturbations and thereby make it possible to analyze the relationship between compounds and gene targets at a genome-wide scale. Current approaches for comparing the expression profiles are based on pairwise connectivity mapping analysis. However, this method makes the simple assumption that the effect of a drug treatment is similar to knocking down its single target gene. Since many compounds can bind multiple targets, the pairwise mapping ignores the combined effects of multiple targets, and therefore fails to detect many potential targets of the compounds.Results
We propose an algorithm to find sets of gene knock-downs that induce gene expression changes similar to a drug treatment. Assuming that the effects of gene knock-downs are additive, we propose a novel bipartite block-wise sparse multi-task learning model with super-graph structure (BBSS-MTL) for multi-target drug repositioning that overcomes the restrictive assumptions of connectivity mapping analysis.Conclusions
The proposed method BBSS-MTL is more accurate for predicting potential drug targets than the simple pairwise connectivity mapping analysis on five datasets generated from different cancer cell lines.Availability
The code can be obtained at http://gr.xjtu.edu.cn/web/liminli/codes.6.
Daniel Cañueto Josep Gómez Reza M. Salek Xavier Correig Nicolau Cañellas 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):24
Introduction
Adoption of automatic profiling tools for 1H-NMR-based metabolomic studies still lags behind other approaches in the absence of the flexibility and interactivity necessary to adapt to the properties of study data sets of complex matrices.Objectives
To provide an open source tool that fully integrates these needs and enables the reproducibility of the profiling process.Methods
rDolphin incorporates novel techniques to optimize exploratory analysis, metabolite identification, and validation of profiling output quality.Results
The information and quality achieved in two public datasets of complex matrices are maximized.Conclusion
rDolphin is an open-source R package (http://github.com/danielcanueto/rDolphin) able to provide the best balance between accuracy, reproducibility and ease of use.7.
Mohammed El-Kebir Benjamin J. Raphael Ron Shamir Roded Sharan Simone Zaccaria Meirav Zehavi Ron Zeira 《Algorithms for molecular biology : AMB》2017,12(1):13
Background
Cancer is an evolutionary process characterized by the accumulation of somatic mutations in a population of cells that form a tumor. One frequent type of mutations is copy number aberrations, which alter the number of copies of genomic regions. The number of copies of each position along a chromosome constitutes the chromosome’s copy-number profile. Understanding how such profiles evolve in cancer can assist in both diagnosis and prognosis.Results
We model the evolution of a tumor by segmental deletions and amplifications, and gauge distance from profile \(\mathbf {a}\) to \(\mathbf {b}\) by the minimum number of events needed to transform \(\mathbf {a}\) into \(\mathbf {b}\). Given two profiles, our first problem aims to find a parental profile that minimizes the sum of distances to its children. Given k profiles, the second, more general problem, seeks a phylogenetic tree, whose k leaves are labeled by the k given profiles and whose internal vertices are labeled by ancestral profiles such that the sum of edge distances is minimum.Conclusions
For the former problem we give a pseudo-polynomial dynamic programming algorithm that is linear in the profile length, and an integer linear program formulation. For the latter problem we show it is NP-hard and give an integer linear program formulation that scales to practical problem instance sizes. We assess the efficiency and quality of our algorithms on simulated instances.Availability
https://github.com/raphael-group/CNT-ILP8.
Background
Today researchers can choose from many bioinformatics protocols for all types of life sciences research, computational environments and coding languages. Although the majority of these are open source, few of them possess all virtues to maximize reuse and promote reproducible science. Wikipedia has proven a great tool to disseminate information and enhance collaboration between users with varying expertise and background to author qualitative content via crowdsourcing. However, it remains an open question whether the wiki paradigm can be applied to bioinformatics protocols.Results
We piloted PyPedia, a wiki where each article is both implementation and documentation of a bioinformatics computational protocol in the python language. Hyperlinks within the wiki can be used to compose complex workflows and induce reuse. A RESTful API enables code execution outside the wiki. Initial content of PyPedia contains articles for population statistics, bioinformatics format conversions and genotype imputation. Use of the easy to learn wiki syntax effectively lowers the barriers to bring expert programmers and less computer savvy researchers on the same page.Conclusions
PyPedia demonstrates how wiki can provide a collaborative development, sharing and even execution environment for biologists and bioinformaticians that complement existing resources, useful for local and multi-center research teams.Availability
PyPedia is available online at: http://www.pypedia.com. The source code and installation instructions are available at: https://github.com/kantale/PyPedia_server. The PyPedia python library is available at: https://github.com/kantale/pypedia. PyPedia is open-source, available under the BSD 2-Clause License.9.
Background
Secondary structures form the scaffold of multiple sequence alignment of non-coding RNA (ncRNA) families. An accurate reconstruction of ancestral ncRNAs must use this structural signal. However, the inference of ancestors of a single ncRNA family with a single consensus structure may bias the results towards sequences with high affinity to this structure, which are far from the true ancestors.Methods
In this paper, we introduce achARNement, a maximum parsimony approach that, given two alignments of homologous ncRNA families with consensus secondary structures and a phylogenetic tree, simultaneously calculates ancestral RNA sequences for these two families.Results
We test our methodology on simulated data sets, and show that achARNement outperforms classical maximum parsimony approaches in terms of accuracy, but also reduces by several orders of magnitude the number of candidate sequences. To conclude this study, we apply our algorithms on the Glm clan and the FinP-traJ clan from the Rfam database.Conclusions
Our results show that our methods reconstruct small sets of high-quality candidate ancestors with better agreement to the two target structures than with classical approaches. Our program is freely available at: http://csb.cs.mcgill.ca/acharnement.10.
Michał Aleksander Ciach Anna Muszewska Paweł Górecki 《Algorithms for molecular biology : AMB》2018,13(1):11
Background
Horizontal gene transfer (HGT), a process of acquisition and fixation of foreign genetic material, is an important biological phenomenon. Several approaches to HGT inference have been proposed. However, most of them either rely on approximate, non-phylogenetic methods or on the tree reconciliation, which is computationally intensive and sensitive to parameter values.Results
We investigate the locus tree inference problem as a possible alternative that combines the advantages of both approaches. We present several algorithms to solve the problem in the parsimony framework. We introduce a novel tree mapping, which allows us to obtain a heuristic solution to the problems of locus tree inference and duplication classification.Conclusions
Our approach allows for faster comparisons of gene and species trees and improves known algorithms for duplication inference in the presence of polytomies in the species trees. We have implemented our algorithms in a software tool available at https://github.com/mciach/LocusTreeInference.11.
Background
The majority of patients with gastric or esophago-gastric cancer are at risk for malnutrition. Preoperative malnutrition was shown to increase the incidence of postoperative complications following abdominal surgery. However, it remains unclear if preoperative parenteral nutritional support during neoadjuvant chemotherapy (NACT) may be effective to reduce the rate of postoperative complications in these patients.Methods/Design
The PERCOG trial is a randomized controlled multicenter observer-blinded trial, investigating if the improvement of the general condition of patients with non-metastasized gastric cancer or cancer of the esophago-gastric junction during NACT by supplemental parenteral nutrition can decrease the postoperative Comprehensive Complication Index (CCI). Statistical analysis of the primary endpoint measure (CCI on postoperative day 30) will be based on the intention-to-treat population. The global level of significance is set at 5% and the sample size (n?=?150) is determined to assure a power of 80%.Discussion
The results of the PERCOG trial will provide high-level evidence for clinical recommendations regarding the administration of preoperative supportive parenteral nutrition and provide all participating patients the opportunity of an improved treatment.Trial registration
German Clinical Trials Register, DRKS00009451. Registered on 3 July 2017.12.
Background
The Healthy Lifestyle Program for women (HeLP-her) is a low-intensity, self-management program which has demonstrated efficacy in preventing excess weight gain in women. However, little is known about the implementation, reach, and sustainability of low-intensity prevention programs in rural settings, where risk for obesity in women is higher than urban settings. We aimed to evaluate a low-intensity healthy lifestyle program delivered to women in a rural setting to inform development of effective community prevention programs.Methods
A mixed method hybrid implementation and evaluation study, guided by the RE-AIM framework (addressing the Reach, Effectiveness, Adoption, Implementation, and Maintenance), was undertaken. Data collection tools included anthropometric measures, program checklists, questionnaires, and semi-structured interviews with participants and local stakeholders. The RE-AIM self-audit tool was applied to assess evaluation rigor.Results
Six hundred and forty-nine women from 41 relatively socio-economic disadvantaged communities in Australia participated: mean age 39.6 years (±SD 6.7) and body mass index of 28.8 kg/m2 (±SD 6.9). A between-group weight difference of ?0.92 kg (95% CI ?1.67 to ?0.16) showed program effectiveness. Reach was broad across 41 towns with 62% of participants reporting influencing some of the health behaviors of their families. Strong implementation fidelity was achieved with good retention rates at 1 year (76%) and high participant satisfaction (82% of participants willing to recommend this program). Over 300 multi-level community partnerships were established supporting high adoption. Stakeholders reported potential capacity to implement and sustain the prevention program in resource poor rural settings, due to the low-intensity design and minimal resources required.Conclusions
Our comprehensive RE-AIM evaluation demonstrates that an evidence-based obesity prevention program can be successfully implemented in real-world settings. The program achieved broad reach, effectiveness, and satisfaction at the community and stakeholder level, revealing potential for program sustainability. The evaluation addressed implementation knowledge gaps to support future obesity prevention program scale-up.Trial registration
Australian and New Zealand Clinical Trial Registry ACTRN 12612000115831 [http://www.anzctr.org.au/].13.
Morten Muhlig Nielsen Paula Tataru Tobias Madsen Asger Hobolth Jakob Skou Pedersen 《Algorithms for molecular biology : AMB》2018,13(1):17
Background
Motif analysis methods have long been central for studying biological function of nucleotide sequences. Functional genomics experiments extend their potential. They typically generate sequence lists ranked by an experimentally acquired functional property such as gene expression or protein binding affinity. Current motif discovery tools suffer from limitations in searching large motif spaces, and thus more complex motifs may not be included. There is thus a need for motif analysis methods that are tailored for analyzing specific complex motifs motivated by biological questions and hypotheses rather than acting as a screen based motif finding tool.Methods
We present Regmex (REGular expression Motif EXplorer), which offers several methods to identify overrepresented motifs in ranked lists of sequences. Regmex uses regular expressions to define motifs or families of motifs and embedded Markov models to calculate exact p-values for motif observations in sequences. Biases in motif distributions across ranked sequence lists are evaluated using random walks, Brownian bridges, or modified rank based statistics. A modular setup and fast analytic p value evaluations make Regmex applicable to diverse and potentially large-scale motif analysis problems.Results
We demonstrate use cases of combined motifs on simulated data and on expression data from micro RNA transfection experiments. We confirm previously obtained results and demonstrate the usability of Regmex to test a specific hypothesis about the relative location of microRNA seed sites and U-rich motifs. We further compare the tool with an existing motif discovery tool and show increased sensitivity.Conclusions
Regmex is a useful and flexible tool to analyze motif hypotheses that relates to large data sets in functional genomics. The method is available as an R package (https://github.com/muhligs/regmex).14.
Shi Yang Li Wei Yu Yao Yong Jin Yuan Wen Shu Tay Nian-Lin Reena Han Rehena Sultana Pryseley N. Assam Alex Tiong-Heng Sia Ban Leong Sng 《BMC anesthesiology》2017,17(1):169
Background
The Supreme? laryngeal mask airway (SLMA) is a single-use LMA with double lumen design that allows separation of the respiratory and the alimentary tract, hence potentially reducing the gastric volume and risk of aspiration. The purpose of this prospective cohort study is to evaluate the the role of the SLMA as an airway technique for women undergoing category 2 and 3 Cesarean delivery under general anesthesia.Methods
We recruited 584 parturients who underwent category 2 or 3 Cesarean delivery under general anesthesia, in which 193 parturients underwent category 2 and 391 parturients underwent category 3 Cesarean delivery. The primary outcome was insertion success rate at 1st attempt in SLMA insertion. The secondary outcomes included anaesthetic, obstetric outcomes and maternal side effects associated with airway device.Results
The 1st attempt insertion success rate was 98.3%, while the overall insertion success rate was 100%. The mean (Standard deviation) time to effective ventilation was 15.6 (4.4) seconds. Orogastric tube insertion was successful at the 1st attempt in all parturients. There was no clinical evidence of aspiration or regurgitation. No episodes of hypoxemia, laryngospasm or bronchospasm were observed intra-operatively. The incidence of complications was low and with good maternal satisfaction reported.Conclusions
The SLMA could be an alternative effective airway in category 2 and 3 parturients emergency Cesarean Delivery under general anesthesia in a carefully-selected obstetric population.Trial registration
Clinical Trials Registration: Clinicaltrials.gov Registration NCT02026882. Registered on December 31, 2013.15.
16.
Ying Wang Guo-Si Li Pei Qiao Ling Lin Hai-Long Xue Li Zhu Mian-Bin Wu Jian-Ping Lin Li-Rong Yang 《Biotechnology letters》2018,40(11-12):1551-1559
Objective
To strengthen NADH regeneration in the biosynthesis of l-2-aminobutyric acid (l-ABA).Results
l-Threonine deaminase (l-TD) from Escherichia coli K12 was modified by directed evolution and rational design to improve its endurance to heat treatment. The half-life of mutant G323D/F510L/T344A at 42 °C increased from 10 to 210 min, a 20-fold increase compared to the wild-type l-TD, and the temperature at which the activity of the enzyme decreased by 50% in 15 min increased from 39 to 53 °C. The mutant together with thermostable l-leucine dehydrogenase from Bacillus sphaericus DSM730 and formate dehydrogenase from Candida boidinii constituted a one-pot system for l-ABA biosynthesis. Employing preheat treatment in the one-pot system, the biosynthesis of l-ABA and total turnover number of NAD+/NADH were 0.993 M and 16,469, in contrast to 0.635 M and 10,531 with wild-type l-TD, respectively.Conclusions
By using the engineered l-TD during endured preheat treatment, the one-pot system has achieved a higher productivity of l-ABA and total turnover number of coenzyme.17.
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.18.
Background
High expectations regarding therapy are reported to have positive effects on future therapeutic course and related behavior. Some individuals are aware of feelings of comfort immediately after a relaxation therapy session.Methods
Heart rate variability biofeedback (HRV-BF) therapy using a relaxation technique called resonant breathing was administered to 44 family caregivers who felt burdened by their work caring for family members with cancer. We prospectively evaluated how the level of comfort participants were aware of immediately after an initial therapy session affected their expectations regarding the therapy, as well as future quality of life (QOL) and autonomic function. This study was a secondary analysis of a randomized, open-label study titled “Self-care system for family caregivers of cancer patients using resonant breathing with a portable home device”.Results
Among the participants, 56.8% were aware of a feeling of comfort immediately after an initial therapy session. Participants were then divided into two groups according to the presence or absence of their awareness of comfort. Expectation levels regarding the therapy were significantly increased in the awareness group after the therapy session (P?=?0.003). No main effect between groups was observed for heart rate variability (HRV) during therapy (P?=?0.949). Four weeks after the initial therapy session, QOL improved and HRV increased in the awareness group (P?<?0.001).Conclusions
Better outcomes in the awareness group were not associated with HRV during therapy. A feeling of comfort immediately after a therapy session may have positive effects on future QOL and autonomic function by raising participants’ expectations of the therapy.Trial registration
UMIN000021639. Registered 27 March 201619.
20.