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| Open AccessGenome sequence and functional genomic analysis of the oil-degrading bacterium Oleispira antarctica
Oleispira antarctica is an oil-degrading bacterium found in the cold and deep sea. Here Kube et al. report the genome sequence of O. antarcticaand provide a comprehensive functional genetic and protein structural analysis, revealing insights into how this organism has adapted to its cold environment.
- Michael Kube
- , Tatyana N. Chernikova
- & Peter N. Golyshin
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Metagenome-wide analysis of antibiotic resistance genes in a large cohort of human gut microbiota
The appearance of antibiotic resistance has been attributed to the misuse of antibiotics. By analysing the diversity of antibiotic resistance genes present in 162 human gut microbiota samples, the authors find that Chinese individuals harbour a larger pool of resistance genes than Spanish or Danish counterparts.
- Yongfei Hu
- , Xi Yang
- & Baoli Zhu
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DNA unmethylome profiling by covalent capture of CpG sites
Chemical modifications of CpG dinucleotides form part of the epigenetic code and various methods for the detection of modified CpG sites exist. Here Kriukiene and colleagues report a complementary method that allows the profiling of unmodified CpG sites within the genome, which they call the 'unmethylome'.
- Edita Kriukienė
- , Viviane Labrie
- & Saulius Klimašauskas
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Article
| Open AccessReconstructing genome evolution in historic samples of the Irish potato famine pathogen
Phytophthora infestanscaused the potato famine in the nineteenth century. Martinet al. sequence the nuclear genomes of five archival samples of the pathogen and compare these to extant specimens allowing the reconstruction of the evolutionary history of P. infestans.
- Michael D. Martin
- , Enrico Cappellini
- & M. Thomas P. Gilbert
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Article
| Open AccessGenome evolution predicts genetic interactions in protein complexes and reveals cancer drug targets
Genetic interactions can reveal insights into cellular functions. Here, Lu et al.show that negative genetic interactions in protein complexes can be predicted by systematically exploring the evolutionary history of genes, which may be useful for the identification of novel targets for anti-cancer drugs.
- Xiaowen Lu
- , Philip R. Kensche
- & Richard A. Notebaart
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| Open AccessEvaluating cell lines as tumour models by comparison of genomic profiles
Cell lines are widely used in cancer research to study tumour biology. Here Domcke et al.compare genomic data from ovarian cancer cell lines with those from clinical ovarian tumour samples and identify cell lines that most closely resemble the genomic features of high-grade serous ovarian cancer.
- Silvia Domcke
- , Rileen Sinha
- & Nikolaus Schultz
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Article
| Open AccessR-loops and nicks initiate DNA breakage and genome instability in non-growing Escherichia coli
DNA double-strand breaks commonly occur in all replicating cells. Wimberly and colleagues show that in non-replicating cells, aborted transcription/translation forms RNA/DNA hybrid R-loops that prime origin-independent replication, leading to DNA breakage, point mutations and chromosomal rearrangements.
- Hallie Wimberly
- , Chandan Shee
- & P. J. Hastings
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Article
| Open AccessAnalysis of elite variety tag SNPs reveals an important allele in upland rice
Quantitative trait loci mapping has traditionally been used to discover desirable alleles in plants. In this study, Lyu et al. use a comparative genome approach to identify an allele that is prevalent in upland rice varieties and alters the function of a protein involved in abscisic acid biosynthesis.
- Jun Lyu
- , Shilai Zhang
- & Wen Wang
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Article
| Open AccessInsights into the role of DNA methylation in diatoms by genome-wide profiling in Phaeodactylum tricornutum
Genome-wide maps of DNA methylation have so far been restricted to plants, animals and fungi. Here, the authors report the first whole-genome methylome of a stramenopile, the diatom Phaeodactylum tricornatum, and provide insight into the evolution of DNA methylation in eukaryotes.
- Alaguraj Veluchamy
- , Xin Lin
- & Leïla Tirichine
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A spontaneous Cdt1 mutation in 129 mouse strains reveals a regulatory domain restraining replication licensing
Cdt1 is part of a protein complex that regulates the initiation of DNA replication. Here Coulombe et al. identify a PEST-like regulatory domain in the N terminus of Cdt1 that prevents premature initiation of DNA synthesis during the cell cycle.
- Philippe Coulombe
- , Damien Grégoire
- & Marcel Méchali
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Wheat Mds-1 encodes a heat-shock protein and governs susceptibility towards the Hessian fly gall midge
Hessian flies are wheat parasites that seize control of the metabolic pathways of their hosts. Liu et al. identify the wheat gene, which encodes a small heat-shock protein, as a major susceptibility gene for infestation by the Hessian fly.
- Xuming Liu
- , Chitvan Khajuria
- & Ming-Shun Chen
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Article
| Open AccessA molecular explanation for the recessive nature of parkin-linked Parkinson’s disease
Mutations in the E3 ubiquitin ligase parkin are associated with juvenile Parkinson’s disease. Here the authors report the solution structure of the Parkin RING2 domain, revealing how disease-associated mutations affect its function and providing a molecular explanation for the recessive nature of the disease.
- Donald E. Spratt
- , R Julio Martinez-Torres
- & Gary S. Shaw
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Genome of the red alga Porphyridium purpureum
Red algae form one of the most ancient eukaryotic lineages, and have undergone multiple symbioses. Here, Price et al. report the first genome sequence for a mesophilic red alga, and reveal significant differences between these organisms and hyperthermopilic algae.
- Debashish Bhattacharya
- , Dana C. Price
- & Hwan Su Yoon
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Stac3 is a component of the excitation–contraction coupling machinery and mutated in Native American myopathy
Skeletal muscle contractions are regulated by a process known as excitation–contraction coupling (ECC), defects in which can cause myopathies. Here Horstick et al.show that the protein STAC3 is a component of the ECC machinery and identify mutations in STAC3 as the cause of Native American Myopathy.
- Eric J. Horstick
- , Jeremy W. Linsley
- & John Y. Kuwada
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Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels
Dehydrated hereditary stomatocytosis is a genetic condition in which the permeability of red blood cells to cations in increased. Albuisson and colleagues find that mutations in the mechanically-activated PIEZO1 ion channel are the major cause of the disease and result in more slowly inactivating currents.
- Juliette Albuisson
- , Swetha E Murthy
- & Ardem Patapoutian
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| Open AccessA European population in Minoan Bronze Age Crete
5,000 years ago, the Minoans established the first advanced civilization of Europe, but their origin remains unclear. Here the authors show that the Minoans were a European population, genetically similar to other ancient European populations and to the present inhabitants of the island of Crete.
- Jeffery R. Hughey
- , Peristera Paschou
- & George Stamatoyannopoulos
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Article
| Open AccessDraft genome sequence of the Tibetan antelope
The endemic Tibetan antelope is adapted to high-altitude environments with low partial pressure of oxygen and high level of ultraviolet radiation. Here Ge et al. report a draft genome of this species and by comparison with other mammals, present possible genetic bases of highland adaptation.
- Ri-Li Ge
- , Qingle Cai
- & Jian Wang
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The genomics of selection in dogs and the parallel evolution between dogs and humans
Dogs may have been domesticated much earlier than previously thought, perhaps by initially scavenging with humans. Here Zhang et al. present genetic evidence that genes positively selected during dog domestication show extensive parallelism with human analogues.
- Guo-dong Wang
- , Weiwei Zhai
- & Ya-ping Zhang
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Periodic Wnt1 expression in response to ecdysteroid generates twin-spot markings on caterpillars
Among various pigmentation patterns on caterpillars, sequential spot markings are often used for aposematic colouration. Fujiwara et al. show using genetic and functional analyses that periodic upregulation of Wnt1 in response to ecdysteroid causes twin-spot markings on lepidopteran larvae.
- Junichi Yamaguchi
- , Yutaka Banno
- & Haruhiko Fujiwara
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Interspecific bacterial sensing through airborne signals modulates locomotion and drug resistance
Microbes use small molecules to sense and communicate with other cells and species. Kim et al. now demonstrate that volatile compounds emitted by Bacillus subtilis can affect Escherichia colimotility and antibiotic resistance through activation of a conserved regulatory mechanism.
- Kwang-sun Kim
- , Soohyun Lee
- & Choong-Min Ryu
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Genomic islands of divergence are not affected by geography of speciation in sunflowers
Differentiated genomic regions among conserved loci, known as speciation islands, are believed to form because of reduced inter-population gene flow near loci under divergent selection. Renault et al.show that reduced recombination, rather than slower gene flow, accounts for the formation of these regions in sunflowers.
- S. Renaut
- , C. J. Grassa
- & L. H. Rieseberg
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The genome of a Mesozoic paleovirus reveals the evolution of hepatitis B viruses
With paleovirology it is possible to identify ancient endogenous viral elements within eukaryotic genomes. Here Suh and colleagues report a genomic record of hepatitis endogenizations through bird’s evolution; they find a complete hepatitis genome sequence, the first discovery of a Mesozoic paleovirus genome.
- Alexander Suh
- , Jürgen Brosius
- & Jan Ole Kriegs
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Neolithic mitochondrial haplogroup H genomes and the genetic origins of Europeans
Here, Brotherton and colleagues sequence 39 mitochondrial genomes from ancient human remains. They track population changes across Central Europe and find that the foundations of the European mitochondrial DNA pool were formed during the Neolithic rather than the post-glacial period.
- Paul Brotherton
- , Wolfgang Haak
- & Janet S. Ziegle
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Max is a repressor of germ cell-related gene expression in mouse embryonic stem cells
Even though both embryonic stem cells and primordial germ cells express pluripotency markers, they differ in their developmental potential. Maeda et al. show that, in embryonic stem cells, the Myc family member Max mediates epigenetic repression of genes involved in germ cell development.
- Ikuma Maeda
- , Daiji Okamura
- & Yasuhisa Matsui
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Article
| Open AccessGenomic deletions disrupt nitrogen metabolism pathways of a cyanobacterial diatom symbiont
Cyanobacterial symbionts of marine diatoms can localize intracellularly or externally to their host partners. Here Hilton et al. describe the genomes of two diazotroph cyanobacterial symbionts of diatoms and show that the location of the symbiont affects expression of nitrogen assimilation genes.
- Jason A. Hilton
- , Rachel A. Foster
- & Tracy A. Villareal
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Article
| Open AccessIdentification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31
Most confirmed susceptibility variants for epithelial ovarian cancer lie in non-protein-coding sequences. Here Permuth-Wey and colleagues investigate variants in 3′ untranslated regions (UTRs) and uncover a new susceptibility locus.
- Jennifer Permuth-Wey
- , Kate Lawrenson
- & Simon A. Gayther
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| Open AccessEpigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer
HNF1B is overexpressed in the clear cell subtype and epigenetically silenced in the serous subtype of ovarian cancer. Pearce and colleagues now show that genetic variants in HNF1B are differentially associated with risks of developing these two cancer subtypes, possibly through an epigenetic mechanism.
- Hui Shen
- , Brooke L. Fridley
- & Celeste Leigh Pearce
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| Open AccessMouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons
Major histocompatibility complex peptide ligands in mouse urine have been hypothesized to serve as signals for communication. In support of this hypothesis, Sturm and colleagues find that specific urinary peptides from genetically different mouse strains can be discriminated by nasal sensory neurons.
- Theo Sturm
- , Trese Leinders-Zufall
- & Hans-Georg Rammensee
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Article
| Open Accessβ-lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity
Sub-lethal concentrations of antibiotics are known to promote mutagenesis of bacterial DNA. Here the authors show that β-lactam antibiotics trigger mutagenesis by upregulating the stress-response protein RpoS, which downregulates mismatch-repair activity.
- A. Gutierrez
- , L. Laureti
- & I. Matic
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Article
| Open AccessWhole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution
The wild rice species can be used as germplasm resources for this crop’s genetic improvement. Here Chen and colleagues report the de novo sequencing of the O. brachyanthagenome, and identify the origin of genome size variation, the role of gene movement and its implications on heterochromatin evolution in the rice genome.
- Jinfeng Chen
- , Quanfei Huang
- & Mingsheng Chen
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Article
| Open AccessA network of genes connects polyglutamine toxicity to ploidy control in yeast
Expansion of polyglutamines correlates with neuronal death in Huntington’s disease. Here the authors show that, in haploid yeast cells, the toxic effect of polyglutamine expression is associated with the disruption of the septin ring and cells may escape from toxicity by hyperploidization.
- Christoph J.O. Kaiser
- , Stefan W. Grötzinger
- & Klaus Richter
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Two sequential cleavage reactions on cruciform DNA structures cause palindrome-mediated chromosomal translocations
Palindromic DNA sequences in the genome can cause gross chromosomal rearrangements. Inagaki et al.demonstrate how the pathways of Holliday-junction resolution and antigen-receptor gene rearrangement interact to process cruciform conformation of palindrome DNA into chromosomal translocations in human embryonic kidney cells.
- Hidehito Inagaki
- , Tamae Ohye
- & Hiroki Kurahashi
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Article
| Open AccessThe interaction between OsMADS57 and OsTB1 modulates rice tillering via DWARF14
Tillering is a multigenic complex trait that influences grain yield in cereal; however, the molecular network for its regulation remains unclear. Guo et al.show that OsMADS57, a transcription factor controlled by miR444a, interacts with OsTEOSINTE BRANCHED1 and targets DWARF14 to control tillering in rice.
- Siyi Guo
- , Yunyuan Xu
- & Kang Chong
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An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells
Patient-specific induced pluripotent stem (iPS) cells hold great potential for regenerative cell therapies. Here Filareto et al. genetically correct iPS cells from mice with muscular dystrophy and use these cells to treat the same animals, providing a proof-of-principle for autologous iPS cell therapy.
- Antonio Filareto
- , Sarah Parker
- & Rita C. R. Perlingeiro
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Article
| Open AccessSir2a regulates rDNA transcription and multiplication rate in the human malaria parasite Plasmodium falciparum
The factors that modulate growth rate of the human malaria parasite Plasmodium falciparum remain poorly understood. Here Scherf and collaborators demonstrate that the Plasmodiumsirtuin PfSir2a regulates the transcription of ribosomal DNA, thereby modulating parasite proliferation rate and virulence.
- Liliana Mancio-Silva
- , Jose Juan Lopez-Rubio
- & Artur Scherf
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| Open AccessDisease mutations in the ryanodine receptor N-terminal region couple to a mobile intersubunit interface
Ryanodine receptors are calcium-release channels located in the membrane of the sarcoplasmic and endoplasmic reticulum. Kimlicka et al.compare pseudo-atomic models of the N-terminal area in the open and closed states and characterize the mutations in the N-terminal that disrupt channel opening.
- Lynn Kimlicka
- , Kelvin Lau
- & Filip Van Petegem
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Article
| Open AccessAllelic variation at a single gene increases food value in a drought-tolerant staple cereal
Sorghum is a drought-adapted cereal, but the grains have lower digestibility than other cereal crops. This work shows that a low-frequency allele type in the starch metabolic gene pullulanase is associated with increased digestibility, which may help improve sorghum yield and therefore food security.
- Edward K. Gilding
- , Celine H. Frère
- & Ian D. Godwin
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Article
| Open AccessGenome of the Chinese tree shrew
The Chinese tree shrew, Tupaia belangeri chinensis, has been proposed as a potential animal model in biomedical research and drug safety testing. This study presents the full genome of the Chinese tree shrew, identifying common features between the tree shrew and primates.
- Yu Fan
- , Zhi-Yong Huang
- & Yong-Gang Yao
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Article
| Open AccessInterferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with severe influenza in Chinese individuals
A variant in the IFITM3gene increases the risk of severe influenza, but homozygosity is rare in Caucasians. The authors show that the variant gene is homozygous in 25% of healthy Chinese people, and 69% of those with severe pandemic influenza, suggesting that this gene influences the epidemiology of influenza in South-East Asia.
- Yong-Hong Zhang
- , Yan Zhao
- & Tao Dong
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Article
| Open AccessHuman CLPP reverts the longevity phenotype of a fungal ClpP deletion strain
The mitochondrial protease CLPP is found in most eukaryotic organisms but its biological role has been unclear. Here Osiewacz and colleagues show that deletion of CLPP extends lifespan of the filamentous fungus Podospora anserina, and that human and fungal CLPP are functionally conserved.
- Fabian Fischer
- , Andrea Weil
- & Heinz D. Osiewacz
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Article
| Open AccessA point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration
Semaphorin 4A is implicated in photoreceptor survival. Nojima and colleagues generate transgenic mice with different mutations in the Sema4A gene and find that point mutation of F350 causes severe degeneration in photoreceptor cells, which can be rescued by virus-mediated gene therapy.
- Satoshi Nojima
- , Toshihiko Toyofuku
- & Atsushi Kumanogoh
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Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming
Recent studies have shown that human induced pluripotent stem cells contain point mutations in coding regions, but the functional significance of these mutations is unclear. Here the authors provide evidence that these mutations are unlikely to confer a selective advantage for reprogramming.
- Sergio Ruiz
- , Athurva Gore
- & Juan Carlos Izpisua Belmonte
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Article
| Open AccessTransgenerational gene silencing causes gain of virulence in a plant pathogen
Plant pathogens encode effector proteins that trigger immunity in plants carrying appropriate resistance genes. Here Qutob et al. show non-Mendelian interactions between naturally occurring Phytophthora sojaealleles that result in transgenerational gene silencing and gain of virulence in soybean plants.
- Dinah Qutob
- , B. Patrick Chapman
- & Mark Gijzen
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Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans
Systemic infection with the fungal pathogenC. albicans is characterized by high mortality, and the precise antifungal defence mechanisms in humans are poorly defined. Using a systems approach, Smeekens et al. describe a previously unknown role for type I interferons in human anti-Candidadefence.
- Sanne P. Smeekens
- , Aylwin Ng
- & Ramnik J. Xavier
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Article
| Open AccessThe genome of Prunus mume
The Prunus mume was domesticated in China over 3,000 years ago and is an important ornamental plant and fruit. Here Qixiang Zhang et al.obtain the first assembly of its genome with a combination of next-generation sequencing, whole-genome mapping and restriction-site-associated DNA.
- Qixiang Zhang
- , Wenbin Chen
- & Jun Wang
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Fluid flow and interlinked feedback loops establish left–right asymmetric decay of Cerl2 mRNA
During embryonic development, midline fluid flow results in asymmetric nodal gene expression. Using genetic manipulations and mathematical modelling, Nakamura et al. find that expression of the nodal antagonist Cerl2 is regulated post-transcriptionally, and that asymmetry is maintained by Wnt-Cerl2 feedback loops.
- Tetsuya Nakamura
- , Daisuke Saito
- & Hiroshi Hamada
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Article
| Open AccessA visible dominant marker for insect transgenesis
Genetic modification in insects mostly involves the use of fluorescent markers to identify successful transformation. Here Osanai-Futahashi et al.report a marker system based on changes in melanin pigmentation that allows the identification of genetically modified insects with the naked eye.
- Mizuko Osanai-Futahashi
- , Takahiro Ohde
- & Hideki Sezutsu
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Cooperation between different RNA virus genomes produces a new phenotype
RNA viruses are known to rapidly evolve new features through errors in replication and reshuffling of genomic segments. These authors report another strategy used by the measles virus to improve infectivity; the cooperation between wild-type and mutant fusion proteins in the same viral particle.
- Yuta Shirogane
- , Shumpei Watanabe
- & Yusuke Yanagi
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A fast and accurate SNP detection algorithm for next-generation sequencing data
The amount of data supplied by next-generation sequencing technologies presents a challenge for traditional algorithms to detect single-nucleotide polymorphisms. Xu et al.develop an efficient detection program and demonstrate its utility by identifying polymorphisms in cancer genomes and human populations.
- Feng Xu
- , Weixin Wang
- & Junwen Wang
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