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1.
Shuo Zhang Caixia Lei Junping Wu Jing Zhou Haiyan Sun Jing Fu Yijuan Sun Xiaoxi Sun Daru Lu Yueping Zhang 《BMC medical genomics》2017,10(1):60
Background
Preimplantation genetic diagnosis (PGD) is now widely used to select embryos free of chromosomal copy number variations (CNV) from chromosome balanced translocation carriers. However, it remains a difficulty to distinguish in embryos between balanced and structurally normal chromosomes efficiently.Methods
For this purpose, genome wide preimplantation genetic haplotyping (PGH) analysis was utilized based on single nucleotide polymorphism (SNP) microarray. SNPs that are heterozygous in the carrier and, homozygous in the carrier’s partner and carrier’s family member are defined as informative SNPs. The haplotypes including the breakpoint regions, the whole chromosomes involved in the translocation and the corresponding homologous chromosomes are established with these informative SNPs in the couple, reference and embryos. In order to perform this analysis, a reference either a translocation carrier’s family member or one unbalanced embryo is required. The positions of translocation breakpoints are identified by molecular karyotypes of unbalanced embryos. The recombination of breakpoint regions in embryos could be identified.Results
Eleven translocation families were enrolled. 68 blastocysts were analyzed, in which 42 were unbalanced or aneuploid and the other 26 were balanced or normal chromosomes. Thirteen embryos were transferred back to patients. Prenatal cytogenetic analysis of amniotic fluid cells was performed. The results predicted by PGH and karyotypes were totally consistent.Conclusions
With the successful clinical application, we demonstrate that PGH was a simple, efficient, and popularized method to distinguish between balanced and structurally normal chromosome embryos.2.
Background
Inference of haplotypes, or the sequence of alleles along the same chromosomes, is a fundamental problem in genetics and is a key component for many analyses including admixture mapping, identifying regions of identity by descent and imputation. Haplotype phasing based on sequencing reads has attracted lots of attentions. Diploid haplotype phasing where the two haplotypes are complimentary have been studied extensively. In this work, we focused on Polyploid haplotype phasing where we aim to phase more than two haplotypes at the same time from sequencing data. The problem is much more complicated as the search space becomes much larger and the haplotypes do not need to be complimentary any more.Results
We proposed two algorithms, (1) Poly-Harsh, a Gibbs Sampling based algorithm which alternatively samples haplotypes and the read assignments to minimize the mismatches between the reads and the phased haplotypes, (2) An efficient algorithm to concatenate haplotype blocks into contiguous haplotypes.Conclusions
Our experiments showed that our method is able to improve the quality of the phased haplotypes over the state-of-the-art methods. To our knowledge, our algorithm for haplotype blocks concatenation is the first algorithm that leverages the shared information across multiple individuals to construct contiguous haplotypes. Our experiments showed that it is both efficient and effective.3.
Jatayev Satyvaldy Kurishbayev Akhylbek Zotova Lyudmila Khasanova Gulmira Serikbay Dauren Zhubatkanov Askar Botayeva Makpal Zhumalin Aibek Turbekova Arysgul Soole Kathleen Langridge Peter Shavrukov Yuri 《BMC plant biology》2017,17(2):254-93
Background
KASP (KBioscience Competitive Allele Specific PCR) and Amplifluor (Amplification with fluorescence) SNP markers are two prominent technologies based upon a shared identical Allele-specific PCR platform.Methods
Amplifluor-like SNP and KASP analysis was carried out using published and own design of Universal probes (UPs) and Gene-specific primers (GSPs).Results
Advantages of the Amplifluor-like system over KASP include the significantly lower costs and much greater flexibility in the adjustment and development of ‘self-designed’ dual fluorescently-labelled UPs and regular GSPs. The presented results include optimisation of ‘tail’ length in UPs and GSPs, protocol adjustment, and the use of various fluorophores in different qPCR instruments. The compatibility of the KASP Master-mix in both original and Amplifluor-like systems has been demonstrated in the presented results, proving their similar principles. Results of SNP scoring with rare alleles in addition to more frequently occurring alleles are shown.Conclusions
The Amplifluor-like system produces SNP genotyping results with a level of sensitivity and accuracy comparable to KASP but at a significantly cheaper cost and with much greater flexibility for UPs with self-designed GSPs.4.
Background
Metabolic syndrome is a risk factor for type 2 diabetes and cardiovascular disease. We identified common genetic variants that alter the risk for metabolic syndrome in the Korean population. To isolate these variants, we conducted a multiple-genotype and multiple-phenotype genome-wide association analysis using the family-based quasi-likelihood score (MFQLS) test. For this analysis, we used 7211 and 2838 genotyped study subjects for discovery and replication, respectively. We also performed a multiple-genotype and multiple-phenotype analysis of a gene-based single-nucleotide polymorphism (SNP) set.Results
We found an association between metabolic syndrome and an intronic SNP pair, rs7107152 and rs1242229, in SIDT2 gene at 11q23.3. Both SNPs correlate with the expression of SIDT2 and TAGLN, whose products promote insulin secretion and lipid metabolism, respectively. This SNP pair showed statistical significance at the replication stage.Conclusions
Our findings provide insight into an underlying mechanism that contributes to metabolic syndrome.5.
Seok?Jin?Kim Hyun?Ae?Jung Shih-Sung?Chuang Huangming?Hong Cheng-Cheng?Guo Junning?Cao Xiao-Nan?Hong Ritsuro?Suzuki Hye?Jin?Kang Jong?Ho?Won Wee-Joo?Chng Yok-Lam?Kwong Cheolwon?Suh Yu-Qin?Song Jun?Zhu Kevin?Tay Soon?Thye?Lim Junji?Suzumiya Tong-Yu?Lin
Background
The gastrointestinal (GI) tract is one of the most common extranasal sites in extranodal NK/T-cell lymphoma (ENKTL). However, data regarding ENKTL involving the GI tract are relatively scarce. Thus, we performed a multicenter, multinational retrospective study to analyze clinical features and treatment outcomes of ENKTL involving the GI tract.Patients and methods
Patients with ENKTL involving the GI tract diagnosed in twelve participating centers between 1991 and 2012 were retrospectively analyzed from five Asian countries.Results
The analysis of 81 patients with ENKTL involving the GI tract revealed that more than 60% of patients presented as advanced disease with B symptoms. 55 patients (68%) had GI manifestations including abdominal pain (n = 26, 32%), GI tract bleeding (n = 17, 21%) and bowel perforation (n = 12, 15%). The most common GI site was the small intestine, including the jejunum and ileum (n = 57, 70.3%). There were 34 patients (42%) who received systemic chemotherapy while 33 patients (41%) underwent surgery plus chemotherapy. However, 35 patients (43%) died due to disease progression, and treatment-related mortality including sepsis occurred in 17 patients (21%). Thus, the median overall survival was 7.8 months (95% Confidence interval: 3.9 – 11.7 months). Patients who could undergo surgery plus chemotherapy showed a trend of better survival than those treated with chemotherapy alone.Conclusion
Overall, the data indicated that ENKTL involving the GI tract has a dismal prognosis despite active treatment including chemotherapy and surgery. Thus, more effective treatment strategies are required for this disease entity.6.
Mohammad Momen Gharibvand Mina Mounesi Arman Shahriari Asghar Sharif Najafi Azim Motamed far Atefeh Roumi 《生物学前沿》2018,13(6):458-463
Background
Diabetes is an important risk factor for atherosclerosis. The diabetic foot is characterized by the presence of arteriopathy and neuropathy. When ischemia is diagnosed, restoration of pulsatile blood flow by revascularization may be considered for salvaging the limb. The treatment options are angioplasty with or without stenting and surgical bypass or hybrid procedures combining the two.Aims
To evaluate the outcomes of severe ischemic diabetic foot ulcers for which percutaneous transluminal angioplasty (PTA) was considered as the first-line vascular procedure. Factors associated with successful PTA were also evaluated.Methods
In 80 consecutive diabetic patients with foot ulcers and severe limb ischemia, PTAwas performed if feasible. All patients were followed until healing or for one year. Clinical and angiographic factors in fluencing outcomes after PTA were sought by univariate and multivariate analysis.Results
PTAwas done in 73 of the 80 (91.2%) patients, and considered clinically succe ssful in 58(79.9%). Successful PTA was significantly higher in patients with Superficial femoral artery, posterior Tibialis and dorsalis pedis arteries involvement in the univariate analysis. Seven patients were expired during the study follow up due to MI, pulmonary thromboembolism and GI bleeding.Conclusion
PTA in diabetic patients with severe ischemic foot ulcers provided favorable. Some parameters could be used for predicting PTA successfulness.7.
Background
In recent years, both single-nucleotide polymorphism (SNP) array and functional magnetic resonance imaging (fMRI) have been widely used for the study of schizophrenia (SCZ). In addition, a few studies have been reported integrating both SNPs data and fMRI data for comprehensive analysis.Methods
In this study, a novel sparse representation based variable selection (SRVS) method has been proposed and tested on a simulation data set to demonstrate its multi-resolution properties. Then the SRVS method was applied to an integrative analysis of two different SCZ data sets, a Single-nucleotide polymorphism (SNP) data set and a functional resonance imaging (fMRI) data set, including 92 cases and 116 controls. Biomarkers for the disease were identified and validated with a multivariate classification approach followed by a leave one out (LOO) cross-validation. Then we compared the results with that of a previously reported sparse representation based feature selection method.Results
Results showed that biomarkers from our proposed SRVS method gave significantly higher classification accuracy in discriminating SCZ patients from healthy controls than that of the previous reported sparse representation method. Furthermore, using biomarkers from both data sets led to better classification accuracy than using single type of biomarkers, which suggests the advantage of integrative analysis of different types of data.Conclusions
The proposed SRVS algorithm is effective in identifying significant biomarkers for complicated disease as SCZ. Integrating different types of data (e.g. SNP and fMRI data) may identify complementary biomarkers benefitting the diagnosis accuracy of the disease.8.
Background
Maximum parsimony phylogenetic tree reconciliation is an important technique for reconstructing the evolutionary histories of hosts and parasites, genes and species, and other interdependent pairs. Since the problem of finding temporally feasible maximum parsimony reconciliations is NP-complete, current methods use either exact algorithms with exponential worst-case running time or heuristics that do not guarantee optimal solutions.Results
We offer an efficient new approach that begins with a potentially infeasible maximum parsimony reconciliation and iteratively “repairs” it until it becomes temporally feasible.Conclusions
In a non-trivial number of cases, this approach finds solutions that are better than those found by the widely-used Jane heuristic.9.
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.10.
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.11.
Background
Restriction site analysis involves determining the locations of restriction sites after the process of digestion by reconstructing their positions based on the lengths of the cut DNA. Using different reaction times with a single enzyme to cut DNA is a technique known as a partial digestion. Determining the exact locations of restriction sites following a partial digestion is challenging due to the computational time required even with the best known practical algorithm.Results
In this paper, we introduce an efficient algorithm to find the exact solution for the partial digest problem. The algorithm is able to find all possible solutions for the input and works by traversing the solution tree with a breadth-first search in two stages and deleting all repeated subproblems. Two types of simulated data, random and Zhang, are used to measure the efficiency of the algorithm. We also apply the algorithm to real data for the Luciferase gene and the E. coli K12 genome.Conclusion
Our algorithm is a fast tool to find the exact solution for the partial digest problem. The percentage of improvement is more than 75% over the best known practical algorithm for the worst case. For large numbers of inputs, our algorithm is able to solve the problem in a suitable time, while the best known practical algorithm is unable.12.
Jack W. KentJr 《BMC genetics》2016,17(Z2):S5
Background
New technologies for acquisition of genomic data, while offering unprecedented opportunities for genetic discovery, also impose severe burdens of interpretation andpenalties for multiple testing.Methods
The Pathway-based Analyses Group of the Genetic Analysis Workshop 19 (GAW19) sought reduction of multiple-testing burden through various approaches to aggregation of highdimensional data in pathways informed by prior biological knowledge.Results
Experimental methods testedincluded the use of "synthetic pathways" (random sets of genes) to estimate power and false-positive error rate of methods applied to simulated data; data reduction via independent components analysis, single-nucleotide polymorphism (SNP)-SNP interaction, and use of gene sets to estimate genetic similarity; and general assessment of the efficacy of prior biological knowledge to reduce the dimensionality of complex genomic data.Conclusions
The work of this group explored several promising approaches to managing high-dimensional data, with the caveat that these methods are necessarily constrained by the quality of external bioinformatic annotation.13.
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.14.
John M. Wentworth Naiara G. Bediaga Megan A. S. Penno Esther Bandala-Sanchez Komal N. Kanojia Konstantinos A. Kouremenos Jennifer J. Couper Leonard C. Harrison ENDIA Study Group 《Metabolomics : Official journal of the Metabolomic Society》2018,14(10):130
Background
Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.Method
Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.Results
Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.Conclusion
Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.15.
Background
Time course measurement of single molecules on a cell surface provides detailed information about the dynamics of the molecules that would otherwise be inaccessible. To extract the quantitative information, single particle tracking (SPT) is typically performed. However, trajectories extracted by SPT inevitably have linking errors when the diffusion speed of single molecules is high compared to the scale of the particle density.Methods
To circumvent this problem, we develop an algorithm to estimate diffusion constants without relying on SPT. The proposed algorithm is based on a probabilistic model of the distance to the nearest point in subsequent frames. This probabilistic model generalizes the model of single particle Brownian motion under an isolated environment into the one surrounded by indistinguishable multiple particles, with a mean field approximation.Results
We demonstrate that the proposed algorithm provides reasonable estimation of diffusion constants, even when other methods suffer due to high particle density or inhomogeneous particle distribution. In addition, our algorithm can be used for visualization of time course data from single molecular measurements.Conclusions
The proposed algorithm based on the probabilistic model of indistinguishable Brownian particles provide accurate estimation of diffusion constants even in the regime where the traditional SPT methods underestimate them due to linking errors.16.
Background
While continental level ancestry is relatively simple using genomic information, distinguishing between individuals from closely associated sub-populations (e.g., from the same continent) is still a difficult challenge.Methods
We study the problem of predicting human biogeographical ancestry from genomic data under resource constraints. In particular, we focus on the case where the analysis is constrained to using single nucleotide polymorphisms (SNPs) from just one chromosome. We propose methods to construct such ancestry informative SNP panels using correlation-based and outlier-based methods.Results
We accessed the performance of the proposed SNP panels derived from just one chromosome, using data from the 1000 Genome Project, Phase 3. For continental-level ancestry classification, we achieved an overall classification rate of 96.75% using 206 single nucleotide polymorphisms (SNPs). For sub-population level ancestry prediction, we achieved an average pairwise binary classification rates as follows: subpopulations in Europe: 76.6% (58 SNPs); Africa: 87.02% (87 SNPs); East Asia: 73.30% (68 SNPs); South Asia: 81.14% (75 SNPs); America: 85.85% (68 SNPs).Conclusion
Our results demonstrate that one single chromosome (in particular, Chromosome 1), if carefully analyzed, could hold enough information for accurate prediction of human biogeographical ancestry. This has significant implications in terms of the computational resources required for analysis of ancestry, and in the applications of such analyses, such as in studies of genetic diseases, forensics, and soft biometrics.17.
Background
GAW20 working group 5 brought together researchers who contributed 7 papers with the aim of evaluating methods to detect genetic by epigenetic interactions. GAW20 distributed real data from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, including single-nucleotide polymorphism (SNP) markers, methylation (cytosine-phosphate-guanine [CpG]) markers, and phenotype information on up to 995 individuals. In addition, a simulated data set based on the real data was provided.Results
The 7 contributed papers analyzed these data sets with a number of different statistical methods, including generalized linear mixed models, mediation analysis, machine learning, W-test, and sparsity-inducing regularized regression. These methods generally appeared to perform well. Several papers confirmed a number of causative SNPs in either the large number of simulation sets or the real data on chromosome 11. Findings were also reported for different SNPs, CpG sites, and SNP–CpG site interaction pairs.Conclusions
In the simulation (200 replications), power appeared generally good for large interaction effects, but smaller effects will require larger studies or consortium collaboration for realizing a sufficient power.18.
Miriam Banas Sindy Neumann Johannes Eiglsperger Eric Schiffer Franz Josef Putz Simone Reichelt-Wurm Bernhard Karl Krämer Philipp Pagel Bernhard Banas 《Metabolomics : Official journal of the Metabolomic Society》2018,14(9):116
Introduction
Allograft rejection is still an important complication after kidney transplantation. Currently, monitoring of these patients mostly relies on the measurement of serum creatinine and clinical evaluation. The gold standard for diagnosing allograft rejection, i.e. performing a renal biopsy is invasive and expensive. So far no adequate biomarkers are available for routine use.Objectives
We aimed to develop a urine metabolite constellation that is characteristic for acute renal allograft rejection.Methods
NMR-Spectroscopy was applied to a training cohort of transplant recipients with and without acute rejection.Results
We obtained a metabolite constellation of four metabolites that shows promising performance to detect renal allograft rejection in the cohorts used (AUC of 0.72 and 0.74, respectively).Conclusion
A metabolite constellation was defined with the potential for further development of an in-vitro diagnostic test that can support physicians in their clinical assessment of a kidney transplant patient.19.
Background
Human mucoepidermoid carcinoma (MEC) is regarded as the most common primary salivary malignancy. High-grade MEC has a high risk of recurrence and poor prognosis. Tumor angiogenesis, induced by poorly differentiated cancer cells of high-grade MEC, contributes to tumor growth and metastasis. Therefore, elucidating molecular mechanisms underlying the pro-angiogenic ability of poorly differentiated MEC cells is critical for the understanding of high-grade MEC progression. It is well known that three-dimensional (3D) cell culture, in contrast with conventional two-dimensional (2D) culture, provides a better approach to in vitro recapitulation of in vivo characteristics of cancer cells and their surrounding microenvironment. The purpose of this study was to model a 3D environment for in vitro gene expression profiling of key molecules in poorly differentiated MEC cells for cancer neovascularization and compared them with traditional 2D cell culture.Methods
Low-passage poorly differentiated MEC cells, derived from human patient samples of high-grade MEC, were microencapsulated in sodium alginate gel microcapsules (3D culture) and compared with cells grown in 2D culture. Cancer cell proliferation was determined by MTT assays for 1 week, and gene expression of VEGF-A, bFGF and TSP-1 was analyzed by western blotting or ELISA. The hypoxic environment in 3D versus 2D culture were assessed by western blotting or immunofluorescence for HIF1α, and the effect of hypoxia on VEGF-A gene expression in 3D cultured cancer cells was assessed by western blotting with the use of the HIF1α inhibitor, 2-methoxyestradiol (2-MeOE2).Results
When encapsulated in alginate gel microcapsules, low-passage poorly differentiated human MEC cells grew in blocks and demonstrated stronger and relatively unlimited proliferation activities. Moreover, significant differences were found in gene expression, with 3D-grown cancer cells a significant increment of VEGF-A and bFGF and a drastic reduction of TSP-1. Consistently, 3D-grown cancer cells secreted significantly more VEGF-A than 2D culture cancer cells. Furthermore, 3D-grown cancer cells showed significantly higher expression of HIF1α, a molecular indicator of hypoxia; the increased expression of VEGF-A in 3D cultured cancer cells was shown to be dependent on the HIF1α activities.Conclusions
The present work shows the effects of 3D culture model by alginate microencapsulation on the proangiogenic potentials of low-passage poorly differentiated human MEC cells. Cancer cells in this 3D system demonstrate significant intensification of key molecular processes for tumor angiogenesis. This is due to a better modeling of the hypoxic tumor microenvironment during 3D culture.20.
Rachel A. Spicer Christoph Steinbeck 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):16