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Artikel: Pangenome graphs in infectious disease: a comprehensive genetic variation analysis of

Yang, Zuyu / Guarracino, Andrea / Biggs, Patrick J / Black, Michael A / Ismail, Nuzla / Wold, Jana Renee / Merriman, Tony R / Prins, Pjotr / Garrison, Erik / de Ligt, Joep

Frontiers in genetics

2023 Band 14, Seite(n) 1225248

Abstract: Whole genome sequencing has revolutionized infectious disease surveillance for tracking and monitoring the spread and evolution of pathogens. However, using a linear reference genome for genomic analyses may introduce biases, especially when studies are ... ...

Abstract	Whole genome sequencing has revolutionized infectious disease surveillance for tracking and monitoring the spread and evolution of pathogens. However, using a linear reference genome for genomic analyses may introduce biases, especially when studies are conducted on highly variable bacterial genomes of the same species. Pangenome graphs provide an efficient model for representing and analyzing multiple genomes and their variants as a graph structure that includes all types of variations. In this study, we present a practical bioinformatics pipeline that employs the PanGenome Graph Builder and the Variation Graph toolkit to build pangenomes from assembled genomes, align whole genome sequencing data and call variants against a graph reference. The pangenome graph enables the identification of structural variants, rearrangements, and small variants (e.g., single nucleotide polymorphisms and insertions/deletions) simultaneously. We demonstrate that using a pangenome graph, instead of a single linear reference genome, improves mapping rates and variant calling for both simulated and real datasets of the pathogen
Sprache	Englisch
Erscheinungsdatum	2023-08-10
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2023.1225248
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Genomic Surveillance of a Globally Circulating Distinct Group W Clonal Complex 11 Meningococcal Variant, New Zealand, 2013-2018.

Yang, Zuyu / Ren, Xiaoyun / Davies, Heather / Wood, Timothy / Lopez, Liza / Sherwood, Jill / Tiong, Audrey / Carter, Philip E

Emerging infectious diseases

2021 Band 27, Heft 4, Seite(n) 1087–1097

Abstract: Genomic surveillance is an essential part of effective disease control, enabling identification of emerging and expanding strains and monitoring of subsequent interventions. Whole-genome sequencing was used to analyze the genomic diversity of all ... ...

Abstract	Genomic surveillance is an essential part of effective disease control, enabling identification of emerging and expanding strains and monitoring of subsequent interventions. Whole-genome sequencing was used to analyze the genomic diversity of all Neisseria meningitidis isolates submitted to the New Zealand Meningococcal Reference Laboratory during 2013-2018. Of the 347 isolates submitted for whole-genome sequencing, we identified 68 sequence types belonging to 18 clonal complexes (CC). The predominant CC was CC41/44; next in predominance was CC11. Comparison of the 45 New Zealand group W CC11 isolates with worldwide representatives of group W CC11 isolates revealed that the original UK strain, the 2013 UK strain, and a distinctive variant (the 2015 strain) were causing invasive group W meningococcal disease in New Zealand. The 2015 strain also demonstrated increased resistance to penicillin and has been circulating in Canada and several countries in Europe, highlighting that close monitoring is needed to prevent future outbreaks around the world.
Mesh-Begriff(e)	Canada ; Europe ; Genomics ; Humans ; Meningococcal Infections ; Neisseria meningitidis ; New Zealand ; Serogroup
Sprache	Englisch
Erscheinungsdatum	2021-04-02
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2704.191716
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Evolution under Spatially Heterogeneous Selection in Solid Tumors.

Li, Guanghao / Yang, Zuyu / Wu, Dafei / Liu, Sixue / Li, Xuening / Li, Tao / Li, Yawei / Liang, Liji / Zou, Weilong / Wu, Chung-I / Wang, Hurng-Yi / Lu, Xuemei

Molecular biology and evolution

2022 Band 39, Heft 1

Abstract: Spatial genetic and phenotypic diversity within solid tumors has been well documented. Nevertheless, how this heterogeneity affects temporal dynamics of tumorigenesis has not been rigorously examined because solid tumors do not evolve as the standard ... ...

Abstract	Spatial genetic and phenotypic diversity within solid tumors has been well documented. Nevertheless, how this heterogeneity affects temporal dynamics of tumorigenesis has not been rigorously examined because solid tumors do not evolve as the standard population genetic model due to the spatial constraint. We therefore, propose a neutral spatial (NS) model whereby the mutation accumulation increases toward the periphery; the genealogical relationship is spatially determined and the selection efficacy is blunted (due to kin competition). In this model, neutral mutations are accrued and spatially distributed in manners different from those of advantageous mutations. Importantly, the distinctions could be blurred in the conventional model. To test the NS model, we performed a three-dimensional multiple microsampling of two hepatocellular carcinomas. Whole-genome sequencing (WGS) revealed a 2-fold increase in mutations going from the center to the periphery. The operation of natural selection can then be tested by examining the spatially determined clonal relationships and the clonal sizes. Due to limited migration, only the expansion of highly advantageous clones can sweep through a large part of the tumor to reveal the selective advantages. Hence, even multiregional sampling can only reveal a fraction of fitness differences in solid tumors. Our results suggest that the NS patterns are crucial for testing the influence of natural selection during tumorigenesis, especially for small solid tumors.
Mesh-Begriff(e)	Carcinogenesis ; Humans ; Mutation ; Neoplasms/genetics ; Selection, Genetic
Sprache	Englisch
Erscheinungsdatum	2022-02-01
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	998579-7
ISSN	1537-1719 ; 0737-4038
ISSN (online)	1537-1719
ISSN	0737-4038
DOI	10.1093/molbev/msab335
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Multi-omics Analysis of Primary Cell Culture Models Reveals Genetic and Epigenetic Basis of Intratumoral Phenotypic Diversity

Liu, Sixue / Yang, Zuyu / Li, Guanghao / Li, Chunyan / Luo, Yanting / Gong, Qiang / Wu, Xin / Li, Tao / Zhang, Zhiqian / Xing, Baocai / Xu, Xiaolan / Lü, Xuemei

Genomics, proteomics & bioinformatics. 2019 Dec., v. 17, no. 6 p.576-589

2019

Abstract: Uncovering the functionally essential variations related to tumorigenesis and tumor progression from cancer genomics data is still challenging due to the genetic diversity among patients, and extensive inter- and intra-tumoral heterogeneity at different ... ...

Abstract	Uncovering the functionally essential variations related to tumorigenesis and tumor progression from cancer genomics data is still challenging due to the genetic diversity among patients, and extensive inter- and intra-tumoral heterogeneity at different levels of gene expression regulation, including but not limited to the genomic, epigenomic, and transcriptional levels. To minimize the impact of germline genetic heterogeneities, in this study, we establish multiple primary cultures from the primary and recurrent tumors of a single patient with hepatocellular carcinoma (HCC). Multi-omics sequencing was performed for these cultures that encompass the diversity of tumor cells from the same patient. Variations in the genome sequence, epigenetic modification, and gene expression are used to infer the phylogenetic relationships of these cell cultures. We find the discrepancy among the relationships revealed by single nucleotide variations (SNVs) and transcriptional/epigenomic profiles from the cell cultures. We fail to find overlap between sample-specific mutated genes and differentially expressed genes (DEGs), suggesting that most of the heterogeneous SNVs among tumor stages or lineages of the patient are functionally insignificant. Moreover, copy number alterations (CNAs) and DNA methylation variation within gene bodies, rather than promoters, are significantly correlated with gene expression variability among these cell cultures. Pathway analysis of CNA/DNA methylation-related genes indicates that a single cell clone from the recurrent tumor exhibits distinct cellular characteristics and tumorigenicity, and such an observation is further confirmed by cellular experiments both in vitro and in vivo. Our systematic analysis reveals that CNAs and epigenomic changes, rather than SNVs, are more likely to contribute to the phenotypic diversity among subpopulations in the tumor. These findings suggest that new therapeutic strategies targeting gene dosage and epigenetic modification should be considered in personalized cancer medicine. This culture model may be applied to the further identification of plausible determinants of cancer metastasis and relapse.
Schlagwörter	DNA ; DNA methylation ; carcinogenesis ; cell culture ; epigenetics ; epigenome ; gene dosage ; gene expression ; gene expression regulation ; genes ; genetic variation ; genomics ; germ cells ; hepatoma ; medicine ; metastasis ; models ; multiomics ; neoplasm progression ; nucleotide sequences ; patients ; phenotypic variation ; phylogeny ; proteomics ; relapse ; therapeutics ; transcription (genetics) ; Intra-individual tumor heterogeneity ; Parallel primary culture ; Multi-omics ; Functional phenotypic diversity
Sprache	Englisch
Erscheinungsverlauf	2019-12
Umfang	p. 576-589.
Erscheinungsort	Elsevier B.V.
Dokumenttyp	Artikel ; Online
Anmerkung	NAL-AP-2-clean ; Resource is Open Access
ZDB-ID	2240213-5
ISSN	2210-3244 ; 1672-0229
ISSN (online)	2210-3244
ISSN	1672-0229
DOI	10.1016/j.gpb.2018.07.008
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel ; Online: Three genome-based phylogeny of Cupressaceae s.l.: further evidence for the evolution of gymnosperms and Southern Hemisphere biogeography.

Yang, Zu-Yu / Ran, Jin-Hua / Wang, Xiao-Quan

Molecular phylogenetics and evolution

2012 Band 64, Heft 3, Seite(n) 452–470

Abstract: Phylogenetic information is essential to interpret the evolution of species. While DNA sequences from different genomes have been widely utilized in phylogenetic reconstruction, it is still difficult to use nuclear genes to reconstruct phylogenies of ... ...

Abstract	Phylogenetic information is essential to interpret the evolution of species. While DNA sequences from different genomes have been widely utilized in phylogenetic reconstruction, it is still difficult to use nuclear genes to reconstruct phylogenies of plant groups with large genomes and complex gene families, such as gymnosperms. Here, we use two single-copy nuclear genes, together with chloroplast and mitochondrial genes, to reconstruct the phylogeny of the ecologically-important conifer family Cupressaceae s.l., based on a complete sampling of its 32 genera. The different gene trees generated are highly congruent in topology, supporting the basal position of Cunninghamia and the seven-subfamily classification, and the estimated divergence times based on different datasets correspond well with each other and with the oldest fossil record. These results imply that we have obtained the species phylogeny of Cupressaceae s.l. In addition, possible origins of all three polyploid conifers were investigated, and a hybrid origin was suggested for Cupressus, Fitzroya and Sequoia. Moreover, we found that the biogeographic history of Cupressaceae s.l. is associated with the separation between Laurasia and Gondwana and the further break-up of the latter. Our study also provides new evidence for the gymnosperm phylogeny.
Mesh-Begriff(e)	Biological Evolution ; Cell Nucleus/genetics ; Cupressaceae/classification ; Cupressaceae/genetics ; DNA, Plant/genetics ; Fossils ; Genes, Chloroplast ; Genes, Mitochondrial ; Genes, Plant ; Genome, Plant ; Likelihood Functions ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA
Chemische Substanzen	DNA, Plant
Sprache	Englisch
Erscheinungsdatum	2012-09
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	33610-5
ISSN	1095-9513 ; 1055-7903
ISSN (online)	1095-9513
ISSN	1055-7903
DOI	10.1016/j.ympev.2012.05.004
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Multi-omics Analysis of Primary Cell Culture Models Reveals Genetic and Epigenetic Basis of Intratumoral Phenotypic Diversity.

Liu, Sixue / Yang, Zuyu / Li, Guanghao / Li, Chunyan / Luo, Yanting / Gong, Qiang / Wu, Xin / Li, Tao / Zhang, Zhiqian / Xing, Baocai / Xu, Xiaolan / Lu, Xuemei

Genomics, proteomics & bioinformatics

2020 Band 17, Heft 6, Seite(n) 576–589

Abstract	Uncovering the functionally essential variations related to tumorigenesis and tumor progression from cancer genomics data is still challenging due to the genetic diversity among patients, and extensive inter- and intra-tumoral heterogeneity at different levels of gene expression regulation, including but not limited to the genomic, epigenomic, and transcriptional levels. To minimize the impact of germline genetic heterogeneities, in this study, we establish multiple primary cultures from the primary and recurrent tumors of a single patient with hepatocellular carcinoma (HCC). Multi-omics sequencing was performed for these cultures that encompass the diversity of tumor cells from the same patient. Variations in the genome sequence, epigenetic modification, and gene expression are used to infer the phylogenetic relationships of these cell cultures. We find the discrepancy among the relationships revealed by single nucleotide variations (SNVs) and transcriptional/epigenomic profiles from the cell cultures. We fail to find overlap between sample-specific mutated genes and differentially expressed genes (DEGs), suggesting that most of the heterogeneous SNVs among tumor stages or lineages of the patient are functionally insignificant. Moreover, copy number alterations (CNAs) and DNA methylation variation within gene bodies, rather than promoters, are significantly correlated with gene expression variability among these cell cultures. Pathway analysis of CNA/DNA methylation-related genes indicates that a single cell clone from the recurrent tumor exhibits distinct cellular characteristics and tumorigenicity, and such an observation is further confirmed by cellular experiments both in vitro and in vivo. Our systematic analysis reveals that CNAs and epigenomic changes, rather than SNVs, are more likely to contribute to the phenotypic diversity among subpopulations in the tumor. These findings suggest that new therapeutic strategies targeting gene dosage and epigenetic modification should be considered in personalized cancer medicine. This culture model may be applied to the further identification of plausible determinants of cancer metastasis and relapse.
Mesh-Begriff(e)	Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; DNA Copy Number Variations ; DNA Methylation ; Epigenomics ; Gene Dosage ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Phenotype ; Phylogeny ; Primary Cell Culture
Sprache	Englisch
Erscheinungsdatum	2020-03-20
Erscheinungsland	China
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2240213-5
ISSN	2210-3244 ; 1672-0229
ISSN (online)	2210-3244
ISSN	1672-0229
DOI	10.1016/j.gpb.2018.07.008
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Building pangenome graphs.

Garrison, Erik / Guarracino, Andrea / Heumos, Simon / Villani, Flavia / Bao, Zhigui / Tattini, Lorenzo / Hagmann, Jörg / Vorbrugg, Sebastian / Marco-Sola, Santiago / Kubica, Christian / Ashbrook, David G / Thorell, Kaisa / Rusholme-Pilcher, Rachel L / Liti, Gianni / Rudbeck, Emilio / Nahnsen, Sven / Yang, Zuyu / Moses, Mwaniki N / Nobrega, Franklin L /

Wu, Yi / Chen, Hao / de Ligt, Joep / Sudmant, Peter H / Soranzo, Nicole / Colonna, Vincenza / Williams, Robert W / Prins, Pjotr

bioRxiv : the preprint server for biology

2023

Abstract: Pangenome graphs can represent all variation between multiple genomes, but existing methods for constructing them are biased due to reference-guided approaches. In response, we have developed PanGenome Graph Builder (PGGB), a reference-free pipeline for ... ...

Abstract	Pangenome graphs can represent all variation between multiple genomes, but existing methods for constructing them are biased due to reference-guided approaches. In response, we have developed PanGenome Graph Builder (PGGB), a reference-free pipeline for constructing unbi-ased pangenome graphs. PGGB uses all-to-all whole-genome alignments and learned graph embeddings to build and iteratively refine a model in which we can identify variation, measure conservation, detect recombination events, and infer phylogenetic relationships.
Sprache	Englisch
Erscheinungsdatum	2023-04-06
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2023.04.05.535718
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Phylogeny and divergence times of gymnosperms inferred from single-copy nuclear genes.

Lu, Ying / Ran, Jin-Hua / Guo, Dong-Mei / Yang, Zu-Yu / Wang, Xiao-Quan

PloS one

2014 Band 9, Heft 9, Seite(n) e107679

Abstract: Phylogenetic reconstruction is fundamental to study evolutionary biology and historical biogeography. However, there was not a molecular phylogeny of gymnosperms represented by extensive sampling at the genus level, and most published phylogenies of this ...

Abstract	Phylogenetic reconstruction is fundamental to study evolutionary biology and historical biogeography. However, there was not a molecular phylogeny of gymnosperms represented by extensive sampling at the genus level, and most published phylogenies of this group were constructed based on cytoplasmic DNA markers and/or the multi-copy nuclear ribosomal DNA. In this study, we use LFY and NLY, two single-copy nuclear genes that originated from an ancient gene duplication in the ancestor of seed plants, to reconstruct the phylogeny and estimate divergence times of gymnosperms based on a complete sampling of extant genera. The results indicate that the combined LFY and NLY coding sequences can resolve interfamilial relationships of gymnosperms and intergeneric relationships of most families. Moreover, the addition of intron sequences can improve the resolution in Podocarpaceae but not in cycads, although divergence times of the cycad genera are similar to or longer than those of the Podocarpaceae genera. Our study strongly supports cycads as the basal-most lineage of gymnosperms rather than sister to Ginkgoaceae, and a sister relationship between Podocarpaceae and Araucariaceae and between Cephalotaxaceae-Taxaceae and Cupressaceae. In addition, intergeneric relationships of some families that were controversial, and the relationships between Taxaceae and Cephalotaxaceae and between conifers and Gnetales are discussed based on the nuclear gene evidence. The molecular dating analysis suggests that drastic extinctions occurred in the early evolution of gymnosperms, and extant coniferous genera in the Northern Hemisphere are older than those in the Southern Hemisphere on average. This study provides an evolutionary framework for future studies on gymnosperms.
Mesh-Begriff(e)	Cell Nucleus/genetics ; Cycadopsida/genetics ; DNA, Ribosomal/genetics ; Evolution, Molecular ; Gene Dosage ; Introns/genetics ; Molecular Sequence Data ; Phylogeny ; Plant Proteins/genetics ; Sequence Analysis, DNA
Chemische Substanzen	DNA, Ribosomal ; Plant Proteins
Sprache	Englisch
Erscheinungsdatum	2014-09-15
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0107679
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Three genome-based phylogeny of Cupressaceae s.l.: Further evidence for the evolution of gymnosperms and Southern Hemisphere biogeography

Yang, Zu-Yu / Ran, Jin-Hua / Wang, Xiao-Quan

Molecular phylogenetics and evolution. 2012 Sept., v. 64, no. 3

2012

Abstract	Phylogenetic information is essential to interpret the evolution of species. While DNA sequences from different genomes have been widely utilized in phylogenetic reconstruction, it is still difficult to use nuclear genes to reconstruct phylogenies of plant groups with large genomes and complex gene families, such as gymnosperms. Here, we use two single-copy nuclear genes, together with chloroplast and mitochondrial genes, to reconstruct the phylogeny of the ecologically-important conifer family Cupressaceae s.l., based on a complete sampling of its 32 genera. The different gene trees generated are highly congruent in topology, supporting the basal position of Cunninghamia and the seven-subfamily classification, and the estimated divergence times based on different datasets correspond well with each other and with the oldest fossil record. These results imply that we have obtained the species phylogeny of Cupressaceae s.l. In addition, possible origins of all three polyploid conifers were investigated, and a hybrid origin was suggested for Cupressus, Fitzroya and Sequoia. Moreover, we found that the biogeographic history of Cupressaceae s.l. is associated with the separation between Laurasia and Gondwana and the further break-up of the latter. Our study also provides new evidence for the gymnosperm phylogeny.
Schlagwörter	Cunninghamia ; Cupressus ; DNA ; Fitzroya ; Sequoia ; biogeography ; chloroplasts ; conifers ; data collection ; fossils ; genes ; hybrids ; nucleotide sequences ; phylogeny ; polyploidy ; topology
Sprache	Englisch
Erscheinungsverlauf	2012-09
Umfang	p. 452-470.
Erscheinungsort	Elsevier Inc.
Dokumenttyp	Artikel
ZDB-ID	33610-5
ISSN	1095-9513 ; 1055-7903
ISSN (online)	1095-9513
ISSN	1055-7903
DOI	10.1016/j.ympev.2012.05.004
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel ; Online: Molecular phylogeny and biogeography of Pseudotsuga (Pinaceae): insights into the floristic relationship between Taiwan and its adjacent areas.

Wei, Xiao-Xin / Yang, Zu-Yu / Li, Yan / Wang, Xiao-Quan

Molecular phylogenetics and evolution

2010 Band 55, Heft 3, Seite(n) 776–785

Abstract: Climatic oscillations and geological events play major roles in shaping species diversity and the distribution of plants. The mechanisms underlying the high level of plant species diversity in eastern Asia are hotly debated. In this study, five cpDNA ... ...

Abstract	Climatic oscillations and geological events play major roles in shaping species diversity and the distribution of plants. The mechanisms underlying the high level of plant species diversity in eastern Asia are hotly debated. In this study, five cpDNA regions, two mtDNA fragments and one nuclear gene (LEAFY) were employed to investigate species diversification and the historical biogeography of Pseudotsuga (Pinaceae), a genus with a typical eastern Asia and western North America disjunct distribution. Both the nuclear LEAFY gene and cpDNA phylogenies strongly suggest that eastern Asian and North American species are monophyletic, respectively. Within the eastern Asia clade, the cpDNA tree placed P. japonica as sister to the rest of the Asian species, but the LEAFY gene tree showed a sister relationship between P. japonica-P. sinensis-P. gaussenii and P. brevifolia-P. forrestii. Molecular dating indicated that the Asian species last shared a common ancestor 20.26+/-5.84 mya and the species diversification of Pseudotsuga was correlated with the Tertiary climatic and tectonic changes. These results, together with the fossil evidence, suggest that Pseudotsuga might have originated from North America and then migrated to eastern Asia by the Bering land bridge during the early Miocene. The Taiwanese species P. wilsoniana harbored two divergent types of LEAFY sequences, which implies that this species might have originated by hybridization between P. brevifolia or its ancestor and the ancestor of P. japonica-P. sinensis-P. gaussenii. Our study also suggests that Taiwan is closely related to both southwest and east China in flora.
Mesh-Begriff(e)	Cell Nucleus/genetics ; DNA, Chloroplast/genetics ; DNA, Mitochondrial/genetics ; DNA, Plant/genetics ; Evolution, Molecular ; Far East ; Genes, Plant ; Genetics, Population ; Geography ; North America ; Phylogeny ; Pseudotsuga/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Taiwan
Chemische Substanzen	DNA, Chloroplast ; DNA, Mitochondrial ; DNA, Plant
Sprache	Englisch
Erscheinungsdatum	2010-06
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	33610-5
ISSN	1095-9513 ; 1055-7903
ISSN (online)	1095-9513
ISSN	1055-7903
DOI	10.1016/j.ympev.2010.03.007
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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