29 results on '"Stinus Lindgreen"'
Search Results
2. Genomic, Transcriptomic, and Phenotypic Analyses of Neisseria meningitidis Isolates from Disease Patients and Their Household Contacts
- Author
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Xiaoyun Ren, David A. Eccles, Gabrielle A. Greig, Jane Clapham, Nicole E. Wheeler, Stinus Lindgreen, Paul P. Gardner, and Joanna K. MacKichan
- Subjects
Neisseria meningitidis ,type IV pili ,carriage ,household contact ,Microbiology ,QR1-502 - Abstract
ABSTRACT Neisseria meningitidis (meningococcus) can cause meningococcal disease, a rapidly progressing and often fatal disease that can occur in previously healthy children. Meningococci are found in healthy carriers, where they reside in the nasopharynx as commensals. While carriage is relatively common, invasive disease, associated with hypervirulent strains, is a comparatively rare event. The basis of increased virulence in some strains is not well understood. New Zealand suffered a protracted meningococcal disease epidemic, from 1991 to 2008. During this time, a household carriage study was carried out in Auckland: household contacts of index meningococcal disease patients were swabbed for isolation of carriage strains. In many households, healthy carriers harbored strains identical, as determined by laboratory typing, to the ones infecting the associated patient. We carried out more-detailed analyses of carriage and disease isolates from a select number of households. We found that isolates, although indistinguishable by laboratory typing methods and likely closely related, had many differences. We identified multiple genome variants and transcriptional differences between isolates. These studies enabled the identification of two new phase-variable genes. We also found that several carriage strains had lost their type IV pili and that this loss correlated with reduced tumor necrosis factor alpha (TNF-α) expression when cultured with epithelial cells. While nonpiliated meningococcal isolates have been previously found in carriage strains, this is the first evidence of an association between type IV pili from meningococci and a proinflammatory epithelial response. We also identified potentially important metabolic differences between carriage and disease isolates, including the sulfate assimilation pathway. IMPORTANCE Neisseria meningitidis causes meningococcal disease but is frequently carried in the throats of healthy individuals; the factors that determine whether invasive disease develops are not completely understood. We carried out detailed studies of isolates, collected from patients and their household contacts, to identify differences between commensal throat isolates and those that caused invasive disease. Though isolates were identical by laboratory typing methods, we uncovered many differences in their genomes, in gene expression, and in their interactions with host cells. In particular, we found that several carriage isolates had lost their type IV pili, a surprising finding since pili are often described as essential for colonization. However, loss of type IV pili correlated with reduced secretion of a proinflammatory cytokine, TNF-α, when meningococci were cocultured with human bronchial epithelial cells; hence, the loss of pili could provide an advantage to meningococci, by resulting in a dampened localized host immune response.
- Published
- 2017
- Full Text
- View/download PDF
3. Nuclear Pore-Like Structures in a Compartmentalized Bacterium.
- Author
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Evgeny Sagulenko, Amanda Nouwens, Richard I Webb, Kathryn Green, Benjamin Yee, Garry Morgan, Andrew Leis, Kuo-Chang Lee, Margaret K Butler, Nicholas Chia, Uyen Thi Phuong Pham, Stinus Lindgreen, Ryan Catchpole, Anthony M Poole, and John A Fuerst
- Subjects
Medicine ,Science - Abstract
Planctomycetes are distinguished from other Bacteria by compartmentalization of cells via internal membranes, interpretation of which has been subject to recent debate regarding potential relations to Gram-negative cell structure. In our interpretation of the available data, the planctomycete Gemmata obscuriglobus contains a nuclear body compartment, and thus possesses a type of cell organization with parallels to the eukaryote nucleus. Here we show that pore-like structures occur in internal membranes of G.obscuriglobus and that they have elements structurally similar to eukaryote nuclear pores, including a basket, ring-spoke structure, and eight-fold rotational symmetry. Bioinformatic analysis of proteomic data reveals that some of the G. obscuriglobus proteins associated with pore-containing membranes possess structural domains found in eukaryote nuclear pore complexes. Moreover, immunogold labelling demonstrates localization of one such protein, containing a β-propeller domain, specifically to the G. obscuriglobus pore-like structures. Finding bacterial pores within internal cell membranes and with structural similarities to eukaryote nuclear pore complexes raises the dual possibilities of either hitherto undetected homology or stunning evolutionary convergence.
- Published
- 2017
- Full Text
- View/download PDF
4. Robust identification of noncoding RNA from transcriptomes requires phylogenetically-informed sampling.
- Author
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Stinus Lindgreen, Sinan Uğur Umu, Alicia Sook-Wei Lai, Hisham Eldai, Wenting Liu, Stephanie McGimpsey, Nicole E Wheeler, Patrick J Biggs, Nick R Thomson, Lars Barquist, Anthony M Poole, and Paul P Gardner
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Noncoding RNAs are integral to a wide range of biological processes, including translation, gene regulation, host-pathogen interactions and environmental sensing. While genomics is now a mature field, our capacity to identify noncoding RNA elements in bacterial and archaeal genomes is hampered by the difficulty of de novo identification. The emergence of new technologies for characterizing transcriptome outputs, notably RNA-seq, are improving noncoding RNA identification and expression quantification. However, a major challenge is to robustly distinguish functional outputs from transcriptional noise. To establish whether annotation of existing transcriptome data has effectively captured all functional outputs, we analysed over 400 publicly available RNA-seq datasets spanning 37 different Archaea and Bacteria. Using comparative tools, we identify close to a thousand highly-expressed candidate noncoding RNAs. However, our analyses reveal that capacity to identify noncoding RNA outputs is strongly dependent on phylogenetic sampling. Surprisingly, and in stark contrast to protein-coding genes, the phylogenetic window for effective use of comparative methods is perversely narrow: aggregating public datasets only produced one phylogenetic cluster where these tools could be used to robustly separate unannotated noncoding RNAs from a null hypothesis of transcriptional noise. Our results show that for the full potential of transcriptomics data to be realized, a change in experimental design is paramount: effective transcriptomics requires phylogeny-aware sampling.
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- 2014
- Full Text
- View/download PDF
5. Rfam: updates to the RNA families database.
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Paul P. Gardner, Jennifer Daub, John G. Tate, Eric P. Nawrocki, Diana L. Kolbe, Stinus Lindgreen, Adam C. Wilkinson, Robert D. Finn, Sam Griffiths-Jones, Sean R. Eddy, and Alex Bateman
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- 2009
- Full Text
- View/download PDF
6. WAR: Webserver for aligning structural RNAs.
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Elfar Torarinsson and Stinus Lindgreen
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- 2008
- Full Text
- View/download PDF
7. MASTR: multiple alignment and structure prediction of non-coding RNAs using simulated annealing.
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Stinus Lindgreen, Paul P. Gardner, and Anders Krogh
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- 2007
- Full Text
- View/download PDF
8. Measuring covariation in RNA alignments: physical realism improves information measures.
- Author
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Stinus Lindgreen, Paul P. Gardner, and Anders Krogh
- Published
- 2006
- Full Text
- View/download PDF
9. Multiple alignment and structure prediction of non-coding RNA sequences.
- Author
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Stinus Lindgreen, Paul P. Gardner, and Anders Krogh
- Published
- 2007
10. Predictors and trajectories of treatment response to SSRIs in patients suffering from PTSD
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Raimund Buller, Stinus Lindgreen, Anne Krogh Nøhr, Mary Hobart, Hans Eriksson, Ida Moltke, and Anders Albrechtsen
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Treatment response ,medicine.medical_specialty ,Anxiety ,Placebo ,Stress Disorders, Post-Traumatic ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,In patient ,Child ,Biological Psychiatry ,Depression (differential diagnoses) ,Sertraline ,Latent growth modeling ,business.industry ,Anxiety Disorders ,Paroxetine ,030227 psychiatry ,Psychiatry and Mental health ,medicine.symptom ,business ,Selective Serotonin Reuptake Inhibitors ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Paroxetine and sertraline are the only FDA approved drugs for treatment of posttraumatic stress disorder (PTSD). Although both drugs show better outcomes than placebo, not all patients benefit from treatment. We examined predictors and latent classes of SSRI treatment response in patients with PTSD. Symptom severity was measured over a 12-week period in 390 patients suffering from PTSD treated with open-label sertraline or paroxetine and a double-blinded placebo. First, growth curve modeling (GCM) was used to examine population-level predictors of treatment response. Second, growth mixture modeling (GMM) was used to group patients into latent classes based on their treatment response trajectories over time and to investigate predictors of latent class membership. Gender, childhood sexual trauma, and sexual assault as index trauma moderated the population-level treatment response using GCM. GMM identified three classes: fast responders, responders with low pretreatment symptom severity and responders with high pretreatment symptom severity. Class membership was predicted based on time since index trauma, severity of depression, and severity of anxiety. The study shows that higher severity of comorbid disorders does not result in an inferior response to treatment and suggests that patients with longer time since index trauma might particularly benefit from treatment with sertraline or paroxetine.
- Published
- 2021
11. Adaptable probabilistic mapping of short reads using position specific scoring matrices.
- Author
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Peter Kerpedjiev, Jes Frellsen, Stinus Lindgreen, and Anders Krogh
- Published
- 2014
- Full Text
- View/download PDF
12. Above and belowground community strategies respond to different global change drivers
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Anthony M. Poole, Karen L. Adair, Stinus Lindgreen, Maud Bernard-Verdier, Jason M. Tylianakis, David A. Wardle, Laura M. Young, and Asian School of the Environment
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0301 basic medicine ,Temperate grassland ,Range (biology) ,media_common.quotation_subject ,lcsh:Medicine ,Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Ecosystem ,lcsh:Science ,media_common ,Plant diversity ,Multidisciplinary ,Community ,Ecology ,lcsh:R ,belowground communities ,Global change ,aboveground communities ,500 Naturwissenschaften und Mathematik::570 Biowissenschaften ,Biologie::570 Biowissenschaften ,Biologie ,communities ,Social sciences::Geography::Environmental sciences [DRNTU] ,030104 developmental biology ,Community Ecology ,Trait ,environmental drivers ,lcsh:Q ,Psychological resilience ,sense organs ,Climate-change Ecology ,030217 neurology & neurosurgery - Abstract
Environmental changes alter the diversity and structure of communities. By shifting the range of species traits that will be successful under new conditions, environmental drivers can also dramatically impact ecosystem functioning and resilience. Above and belowground communities jointly regulate whole-ecosystem processes and responses to change, yet they are frequently studied separately. To determine whether these communities respond similarly to environmental changes, we measured taxonomic and trait-based responses of plant and soil microbial communities to four years of experimental warming and nitrogen deposition in a temperate grassland. Plant diversity responded strongly to N addition, whereas soil microbial communities responded primarily to warming, likely via an associated decrease in soil moisture. These above and belowground changes were associated with selection for more resource-conservative plant and microbe growth strategies, which reduced community functional diversity. Functional characteristics of plant and soil microbial communities were weakly correlated (P = 0.07) under control conditions, but not when above or belowground communities were altered by either global change driver. These results highlight the potential for global change drivers operating simultaneously to have asynchronous impacts on above and belowground components of ecosystems. Assessment of a single ecosystem component may therefore greatly underestimate the whole-system impact of global environmental changes.
- Published
- 2019
13. Author Correction: An evaluation of the accuracy and speed of metagenome analysis tools
- Author
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Karen L. Adair, Stinus Lindgreen, and Paul P. Gardner
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Multidisciplinary ,Information retrieval ,Metagenomics ,Computer science ,Published Erratum ,lcsh:R ,MEDLINE ,lcsh:Medicine ,lcsh:Q ,Analysis tools ,lcsh:Science - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2020
14. Genomic, Transcriptomic, and Phenotypic Analyses of Neisseria meningitidis Isolates from Disease Patients and Their Household Contacts
- Author
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Paul P. Gardner, Xiaoyun Ren, Jane Clapham, David Eccles, Stinus Lindgreen, Gabrielle A. Greig, Joanna K. MacKichan, and Nicole E. Wheeler
- Subjects
0301 basic medicine ,Physiology ,household contact ,030106 microbiology ,lcsh:QR1-502 ,Virulence ,Disease ,Neisseria meningitidis ,Biology ,medicine.disease_cause ,Meningococcal disease ,Biochemistry ,Microbiology ,lcsh:Microbiology ,Pilus ,03 medical and health sciences ,Genetics ,medicine ,Typing ,Sulfate assimilation ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,carriage ,type IV pili ,medicine.disease ,QR1-502 ,3. Good health ,Computer Science Applications ,030104 developmental biology ,Carriage ,Modeling and Simulation - Abstract
Neisseria meningitidis (meningococcus) can cause meningococcal disease, a rapidly progressing and often fatal disease that can occur in previously healthy children. Meningococci are found in healthy carriers, where they reside in the nasopharynx as commensals. While carriage is relatively common, invasive disease, associated with hypervirulent strains, is a comparatively rare event. The basis of increased virulence in some strains is not well understood. New Zealand suffered a protracted meningococcal disease epidemic, from 1991 to 2008. During this time, a household carriage study was carried out in Auckland: household contacts of index meningococcal disease patients were swabbed for isolation of carriage strains. In many households, healthy carriers harbored strains identical, as determined by laboratory typing, to the ones infecting the associated patient. We carried out more-detailed analyses of carriage and disease isolates from a select number of households. We found that isolates, although indistinguishable by laboratory typing methods and likely closely related, had many differences. We identified multiple genome variants and transcriptional differences between isolates. These studies enabled the identification of two new phase-variable genes. We also found that several carriage strains had lost their type IV pili and that this loss correlated with reduced tumor necrosis factor alpha (TNF-α) expression when cultured with epithelial cells. While nonpiliated meningococcal isolates have been previously found in carriage strains, this is the first evidence of an association between type IV pili from meningococci and a proinflammatory epithelial response. We also identified potentially important metabolic differences between carriage and disease isolates, including the sulfate assimilation pathway. IMPORTANCE Neisseria meningitidis causes meningococcal disease but is frequently carried in the throats of healthy individuals; the factors that determine whether invasive disease develops are not completely understood. We carried out detailed studies of isolates, collected from patients and their household contacts, to identify differences between commensal throat isolates and those that caused invasive disease. Though isolates were identical by laboratory typing methods, we uncovered many differences in their genomes, in gene expression, and in their interactions with host cells. In particular, we found that several carriage isolates had lost their type IV pili, a surprising finding since pili are often described as essential for colonization. However, loss of type IV pili correlated with reduced secretion of a proinflammatory cytokine, TNF-α, when meningococci were cocultured with human bronchial epithelial cells; hence, the loss of pili could provide an advantage to meningococci, by resulting in a dampened localized host immune response.
- Published
- 2017
15. Nuclear pore-like structures in a compartmentalized bacterium
- Author
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Garry Morgan, Benjamin K. Yee, Evgeny Sagulenko, Anthony M. Poole, Kathryn Green, Stinus Lindgreen, Ryan J. Catchpole, Richard I. Webb, Nicholas Chia, John A. Fuerst, Kuo-Chang Lee, Andrew Leis, Margaret K. Butler, Uyen Thi Phuong Pham, and Amanda Nouwens
- Subjects
Models, Molecular ,Proteomics ,Protein Structure Comparison ,0301 basic medicine ,Proteome ,Protein Conformation ,Membrane Protein Complexes ,Cell Membranes ,lcsh:Medicine ,Protein Structure Prediction ,Negative Staining ,Biochemistry ,Homology (biology) ,Protein structure ,0302 clinical medicine ,Cell Wall ,Cell Compartmentation ,Macromolecular Structure Analysis ,Fractionation ,Nuclear pore ,lcsh:Science ,Staining ,0303 health sciences ,Multidisciplinary ,biology ,Chemistry ,Planctomycetes ,Eukaryota ,Biological Evolution ,Cell biology ,Membrane Staining ,Separation Processes ,medicine.anatomical_structure ,Membrane ,Eukaryote ,Cellular Structures and Organelles ,Research Article ,Protein Structure ,030106 microbiology ,Research and Analysis Methods ,03 medical and health sciences ,Imaging, Three-Dimensional ,Bacterial Proteins ,Nuclear Membrane ,medicine ,Nuclear membrane ,Molecular Biology ,030304 developmental biology ,Cell Nucleus ,Bacteria ,lcsh:R ,Computational Biology ,Biology and Life Sciences ,Proteins ,Membrane Proteins ,Protein Complexes ,Intracellular Membranes ,Cell Biology ,Internal cell ,biology.organism_classification ,Planctomycetales ,030104 developmental biology ,Specimen Preparation and Treatment ,Nuclear Pore ,Biophysics ,lcsh:Q ,Nucleus ,030217 neurology & neurosurgery - Abstract
Planctomycetes are distinguished from other Bacteria by compartmentalization of cells via internal membranes, interpretation of which has been subject to recent debate regarding potential relations to Gram-negative cell structure. In our interpretation of the available data, the planctomycete Gemmata obscuriglobus contains a nuclear body compartment, and thus possesses a type of cell organization with parallels to the eukaryote nucleus. Here we show that pore-like structures occur in internal membranes of G.obscuriglobus and that they have elements structurally similar to eukaryote nuclear pores, including a basket, ring-spoke structure, and eight-fold rotational symmetry. Bioinformatic analysis of proteomic data reveals that some of the G. obscuriglobus proteins associated with pore-containing membranes possess structural domains found in eukaryote nuclear pore complexes. Moreover, immuno-gold labelling demonstrates localization of one such protein, containing a β-propeller domain, specifically to the G. obscuriglobus pore-like structures. Finding bacterial pores within internal cell membranes and with structural similarities to eukaryote nuclear pore complexes raises the dual possibilities of either hitherto undetected homology or stunning evolutionary convergence.
- Published
- 2016
16. Microsatellite records for volume 8, issue 2
- Author
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Dareen Almojil, Maria Cristina Arias, Rochelle R. Beasley, Yiyong Chen, Rulon W. Clark, Yinghui Dong, Zhiguo Dong, Natalie Forsdick, Elaine Françoso, E. González-Ortegón, A. M. González-Tizón, Linsheng Gui, Huayang Guo, Hongfang Guo, Marie L. Hale, Shigui Jiang, Kenneth L. Jones, Stacey L. Lance, Yi Lei, Jiuxuan Li, Xiaoyan Li, Haotian Li, Chuanwu Li, Xiaoying Li, Jiale Li, Zongqiang Lian, Zhiqiang Liang, Stinus Lindgreen, Tiantian Liu, Mingqiu Liu, Zhihong Liu, Xiaojun Liu, Yongqiang Lu, Tianshu Lv, Qingzhan Ma, Wenming Ma, A. Martínez-Lage, Melanie Massaro, Donghong Niu, A. Perina, Mauro Ramalho, Paulo Cseri Ricardo, Stephen E. Rice, Priscila Karla Ferreira Santos, Weilai Sha, Maise Silva, Zhaobin Song, Xiujun Sun, A. Vizcaíno, Yaning Wang, Xiaoyu Wang, Chongrui Wang, Chenghe Wang, Dawei Wei, Xudong Wu, Biao Wu, Xing Xiang, Shuyu Xue, Aiguo Yang, Xiping Yuan, Linsen Zan, Aibin Zhan, Nan Zhang, Dianchang Zhang, Huanxin Zhang, Jiupan Zhang, Le Zhang, Guangming Zhang, Honghai Zhang, Zaiyong Zhang, Chao Zhao, Yu Zhou, Liqing Zhou, Kecheng Zhu, and Wanchao Zhu
- Subjects
education ,Genetics ,Ecology, Evolution, Behavior and Systematics - Published
- 2016
17. An evaluation of the accuracy and speed of metagenome analysis tools
- Author
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Karen L. Adair, Paul P. Gardner, and Stinus Lindgreen
- Subjects
0301 basic medicine ,Multidisciplinary ,Computer science ,Shotgun sequencing ,Scale (chemistry) ,030106 microbiology ,Gastrointestinal Microbiome ,Computational Biology ,High-Throughput Nucleotide Sequencing ,Data science ,Article ,03 medical and health sciences ,030104 developmental biology ,Metagenomics ,Benchmark (computing) ,Humans ,Metagenome ,Analysis tools ,Author Correction ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Ecosystem ,Software ,Skin - Abstract
Metagenome studies are becoming increasingly widespread, yielding important insights into microbial communities covering diverse environments from terrestrial and aquatic ecosystems to human skin and gut. With the advent of high-throughput sequencing platforms, the use of large scale shotgun sequencing approaches is now commonplace. However, a thorough independent benchmark comparing state-of-the-art metagenome analysis tools is lacking. Here, we present a benchmark where the most widely used tools are tested on complex, realistic data sets. Our results clearly show that the most widely used tools are not necessarily the most accurate, that the most accurate tool is not necessarily the most time consuming and that there is a high degree of variability between available tools. These findings are important as the conclusions of any metagenomics study are affected by errors in the predicted community composition and functional capacity. Data sets and results are freely available from http://www.ucbioinformatics.org/metabenchmark.html
- Published
- 2016
- Full Text
- View/download PDF
18. AdapterRemoval v2:rapid adapter trimming, identification, and read merging
- Author
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Ludovic Orlando, Mikkel Schubert, and Stinus Lindgreen
- Subjects
0106 biological sciences ,0301 basic medicine ,Data pre-processing ,Computer science ,Adapter trimming ,010603 evolutionary biology ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Sequence alignment ,Technical Note ,SIMD ,SSE2 ,Throughput (business) ,Medicine(all) ,High-throughput sequencing ,Base Sequence ,Adapter (computing) ,business.industry ,Biochemistry, Genetics and Molecular Biology(all) ,Process (computing) ,High-Throughput Nucleotide Sequencing ,General Medicine ,Adapter identification ,Identification (information) ,030104 developmental biology ,Trimming ,business ,Algorithms ,Computer hardware - Abstract
Background As high-throughput sequencing platforms produce longer and longer reads, sequences generated from short inserts, such as those obtained from fossil and degraded material, are increasingly expected to contain adapter sequences. Efficient adapter trimming algorithms are also needed to process the growing amount of data generated per sequencing run. Findings We introduce AdapterRemoval v2, a major revision of AdapterRemoval v1, which introduces (i) striking improvements in throughput, through the use of single instruction, multiple data (SIMD; SSE1 and SSE2) instructions and multi-threading support, (ii) the ability to handle datasets containing reads or read-pairs with different adapters or adapter pairs, (iii) simultaneous demultiplexing and adapter trimming, (iv) the ability to reconstruct adapter sequences from paired-end reads for poorly documented data sets, and (v) native gzip and bzip2 support. Conclusions We show that AdapterRemoval v2 compares favorably with existing tools, while offering superior throughput to most alternatives examined here, both for single and multi-threaded operations. Electronic supplementary material The online version of this article (doi:10.1186/s13104-016-1900-2) contains supplementary material, which is available to authorized users.
- Published
- 2016
19. Ancient human genome sequence of an extinct Palaeo-Eskimo
- Author
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Michael Bunce, Jing Zhao, Rasmus Nielsen, Paula F. Campos, M. Thomas P. Gilbert, Finn Cilius Nielsen, Yingrui Li, Anders Albrechtsen, Mads Bak, Eske Willerslev, Morten Rasmussen, Bjarne Grønnow, Ene Metspalu, Stinus Lindgreen, Tracey Pierre, Ramneek Gupta, Ludmila P. Osipova, Andrew Gledhill, Hanne Munkholm Kamp, Michael H. Crawford, Eline D. Lorenzen, Thomas Sicheritz-Pontén, Christian Bendixen, Toomas Kivisild, S. A. Fedorova, Richard Villems, Marcelo Bertalan, Minfeng Chen, Jakob Skou Pedersen, Andrew Wilson, Morten Meldgaard, Hao Zhang, Kasper Nielsen, Søren Brunak, Thomas Higham, Xiuqing Zhang, Silvana R. Tridico, Xiaosen Guo, Zhuo Li, Thomas Hansen, Jun Wang, Yong Wang, Mait Metspalu, Maanasa Raghavan, Jonas Binladen, Karsten Kristiansen, Anders Krogh, Niels Tommerup, Claus Andreasen, Ida Moltke, Ludovic Orlando, and Christopher Bronk Ramsey
- Subjects
Male ,Genotype ,Sequence analysis ,Paleo-Eskimo ,Greenland ,Population ,Genomics ,Single-nucleotide polymorphism ,Biology ,Inuits ,Extinction, Biological ,Polymorphism, Single Nucleotide ,Genome ,Article ,03 medical and health sciences ,0302 clinical medicine ,Humans ,education ,History, Ancient ,Phylogeny ,030304 developmental biology ,Cryopreservation ,Genetics ,Whole genome sequencing ,0303 health sciences ,education.field_of_study ,Multidisciplinary ,Genome, Human ,Sequence Analysis, DNA ,Emigration and Immigration ,Siberia ,Genetics, Population ,Phenotype ,Inuit ,Human genome ,030217 neurology & neurosurgery ,Hair - Abstract
We report here the genome sequence of an ancient human. Obtained from approximately 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20x, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.
- Published
- 2010
20. Rfam: updates to the RNA families database
- Author
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Jennifer Daub, Diana L. Kolbe, Robert D. Finn, Eric P. Nawrocki, John Tate, Paul P. Gardner, Stinus Lindgreen, Sam Griffiths-Jones, Alex Bateman, Sean R. Eddy, and Adam C. Wilkinson
- Subjects
Genetics ,Internet ,0303 health sciences ,Sequence Analysis, RNA ,030306 microbiology ,Sequence analysis ,RNA ,Rfam ,Sequence alignment ,Articles ,Computational biology ,Ribosomal RNA ,Biology ,Genome ,03 medical and health sciences ,Stockholm format ,Computer Graphics ,Small nucleolar RNA ,Databases, Nucleic Acid ,Sequence Alignment ,030304 developmental biology - Abstract
Rfam is a collection of RNA sequence families, represented by multiple sequence alignments and covariance models (CMs). The primary aim of Rfam is to annotate new members of known RNA families on nucleotide sequences, particularly complete genomes, using sensitive BLAST filters in combination with CMs. A minority of families with a very broad taxonomic range (e.g. tRNA and rRNA) provide the majority of the sequence annotations, whilst the majority of Rfam families (e.g. snoRNAs and miRNAs) have a limited taxonomic range and provide a limited number of annotations. Recent improvements to the website, methodologies and data used by Rfam are discussed. Rfam is freely available on the Web at http://rfam.sanger.ac.uk/and http://rfam.janelia.org/.
- Published
- 2009
- Full Text
- View/download PDF
21. SNPest: a probabilistic graphical model for estimating genotypes
- Author
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Anders Krogh, Stinus Lindgreen, and Jakob Skou Pedersen
- Subjects
Genotyping ,Genotype ,Population ,Posterior probability ,SNP ,Inference ,Haploidy ,Biology ,computer.software_genre ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,DNA sequencing ,Illumina ,Gene Frequency ,Software Design ,Technical Note ,Escherichia coli ,Humans ,Computer Simulation ,Graphical model ,education ,Genetic Association Studies ,Probability ,Medicine(all) ,Genetics ,education.field_of_study ,Models, Statistical ,Ancient DNA ,Genome, Human ,Biochemistry, Genetics and Molecular Biology(all) ,Probabilistic logic ,High-Throughput Nucleotide Sequencing ,Reproducibility of Results ,General Medicine ,Diploidy ,Phenotype ,Next-generation sequencing ,Human genome ,Data mining ,computer ,Genome, Bacterial - Abstract
Background As the use of next-generation sequencing technologies is becoming more widespread, the need for robust software to help with the analysis is growing as well. A key challenge when analyzing sequencing data is the prediction of genotypes from the reads, i.e. correct inference of the underlying DNA sequences that gave rise to the sequenced fragments. For diploid organisms, the genotyper should be able to predict both alleles in the individual. Variations between the individual and the population can then be analyzed by looking for SNPs (single nucleotide polymorphisms) in order to investigate diseases or phenotypic features. To perform robust and high confidence genotyping and SNP calling, methods are needed that take the technology specific limitations into account and can model different sources of error. As an example, ancient DNA poses special challenges as the data is often shallow and subject to errors induced by post mortem damage. Findings We present a novel approach to the genotyping problem where a probabilistic framework describing the process from sampling to sequencing is implemented as a graphical model. This makes it possible to model technology specific errors and other sources of variation that can affect the result. The inferred genotype is given a posterior probability to signify the confidence in the result. SNPest has already been used to genotype large scale projects such as the first ancient human genome published in 2010. Conclusions We compare the performance of SNPest to a number of other widely used genotypers on both real and simulated data, covering both haploid and diploid genomes. We investigate the effects of read depth, of removing adapters before mapping and genotyping, of using different mapping tools, and of using the correct model in the genotyping process. We show that the performance of SNPest is comparable to existing methods, and we also illustrate cases where SNPest has an advantage over other methods, e.g. when dealing with simulated ancient DNA. Electronic supplementary material The online version of this article (doi:10.1186/1756-0500-7-698) contains supplementary material, which is available to authorized users.
- Published
- 2014
22. Adaptable probabilistic mapping of short reads using position specific scoring matrices
- Author
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Stinus Lindgreen, Anders Krogh, Peter Kerpedjiev, and Jes Frellsen
- Subjects
Biology ,computer.software_genre ,Data type ,Biochemistry ,Evolution, Molecular ,Software ,Sequence alignment ,Structural Biology ,Animals ,Humans ,Position-Specific Scoring Matrices ,Limit (mathematics) ,Sensitivity (control systems) ,Molecular Biology ,Probability ,Measure (data warehouse) ,Genome ,Short-read mapping ,Ancient DNA ,business.industry ,Applied Mathematics ,Probabilistic logic ,Sequence Analysis, DNA ,PAR-CLIP ,Computer Science Applications ,Xeno mapping ,Next-generation sequencing ,Drosophila ,Data mining ,business ,computer ,Reference genome ,Research Article - Abstract
Background Modern DNA sequencing methods produce vast amounts of data that often requires mapping to a reference genome. Most existing programs use the number of mismatches between the read and the genome as a measure of quality. This approach is without a statistical foundation and can for some data types result in many wrongly mapped reads. Here we present a probabilistic mapping method based on position-specific scoring matrices, which can take into account not only the quality scores of the reads but also user-specified models of evolution and data-specific biases. Results We show how evolution, data-specific biases, and sequencing errors are naturally dealt with probabilistically. Our method achieves better results than Bowtie and BWA on simulated and real ancient and PAR-CLIP reads, as well as on simulated reads from the AT rich organism P. falciparum, when modeling the biases of these data. For simulated Illumina reads, the method has consistently higher sensitivity for both single-end and paired-end data. We also show that our probabilistic approach can limit the problem of random matches from short reads of contamination and that it improves the mapping of real reads from one organism (D. melanogaster) to a related genome (D. simulans). Conclusion The presented work is an implementation of a novel approach to short read mapping where quality scores, prior mismatch probabilities and mapping qualities are handled in a statistically sound manner. The resulting implementation provides not only a tool for biologists working with low quality and/or biased sequencing data but also a demonstration of the feasibility of using a probability based alignment method on real and simulated data sets.
- Published
- 2014
23. Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome
- Author
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Peter A. Jones, Theresa K. Kelly, Anders Krogh, Morten Rasmussen, Eivind Valen, Cindi A. Hoover, Robin Andersson, Brian J. Parker, Egor Prokhortchouk, Jakob Skou Pedersen, Desmond J. Tobin, Edward M. Rubin, Eske Willerslev, Alexei Tikhonov, Stinus Lindgreen, Amhed Missael Vargas Velazquez, M. Thomas P. Gilbert, Søren Vang, Ludovic Orlando, Berit Lilje, and Albin Sandelin
- Subjects
Epigenomics ,Method ,Gene Expression ,Biology ,Genome ,Epigenesis, Genetic ,Evolution, Molecular ,Cytosine ,Genetics ,Animals ,Humans ,Nucleosome ,Epigenetics ,Promoter Regions, Genetic ,Phylogeny ,Genetics (clinical) ,Whole genome sequencing ,aDNA nucleosomes methylation ,Genome, Human ,Chromosome Mapping ,Sequence Analysis, DNA ,DNA Methylation ,Nucleosomes ,Ancient DNA ,Gene Expression Regulation ,Inuit ,Evolutionary biology ,DNA methylation ,Human genome - Abstract
Epigenetic information is available from contemporary organisms, but is difficult to track back in evolutionary time. Here, we show that genome-wide epigenetic information can be gathered directly from next-generation sequence reads of DNA isolated from ancient remains. Using the genome sequence data generated from hair shafts of a 4000-yr-old Paleo-Eskimo belonging to the Saqqaq culture, we generate the first ancient nucleosome map coupled with a genome-wide survey of cytosine methylation levels. The validity of both nucleosome map and methylation levels were confirmed by the recovery of the expected signals at promoter regions, exon/intron boundaries, and CTCF sites. The top-scoring nucleosome calls revealed distinct DNA positioning biases, attesting to nucleotide-level accuracy. The ancient methylation levels exhibited high conservation over time, clustering closely with modern hair tissues. Using ancient methylation information, we estimated the age at death of the Saqqaq individual and illustrate how epigenetic information can be used to infer ancient gene expression. Similar epigenetic signatures were found in other fossil material, such as 110,000- to 130,000-yr-old bones, supporting the contention that ancient epigenomic information can be reconstructed from a deep past. Our findings lay the foundation for extracting epigenomic information from ancient samples, allowing shifts in epialleles to be tracked through evolutionary time, as well as providing an original window into modern epigenomics.
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- 2014
24. AdapterRemoval: easy cleaning of next-generation sequencing reads
- Author
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Stinus Lindgreen
- Subjects
FASTQ format ,Data pre-processing ,Computer science ,Single-end reads ,Sequencing data ,lcsh:Medicine ,Adapter trimming ,computer.software_genre ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Trim ,DNA sequencing ,Sequence alignment ,Technical Note ,Paired-end reads ,lcsh:Science (General) ,lcsh:QH301-705.5 ,Medicine(all) ,Biochemistry, Genetics and Molecular Biology(all) ,Adapter (computing) ,lcsh:R ,Sequence Analysis, DNA ,General Medicine ,lcsh:Biology (General) ,Next-generation sequencing ,Trimming ,Data mining ,computer ,Algorithms ,lcsh:Q1-390 - Abstract
Background With the advent of next-generation sequencing there is an increased demand for tools to pre-process and handle the vast amounts of data generated. One recurring problem is adapter contamination in the reads, i.e. the partial or complete sequencing of adapter sequences. These adapter sequences have to be removed as they can hinder correct mapping of the reads and influence SNP calling and other downstream analyses. Findings We present a tool called AdapterRemoval which is able to pre-process both single and paired-end data. The program locates and removes adapter residues from the reads, it is able to combine paired reads if they overlap, and it can optionally trim low-quality nucleotides. Furthermore, it can look for adapter sequence in both the 5’ and 3’ ends of the reads. This is a flexible tool that can be tuned to accommodate different experimental settings and sequencing platforms producing FASTQ files. AdapterRemoval is shown to be good at trimming adapters from both single-end and paired-end data. Conclusions AdapterRemoval is a comprehensive tool for analyzing next-generation sequencing data. It exhibits good performance both in terms of sensitivity and specificity. AdapterRemoval has already been used in various large projects and it is possible to extend it further to accommodate application-specific biases in the data.
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- 2012
25. Measuring covariation in RNA alignments: physical realism improves information measures
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Anders Krogh, Stinus Lindgreen, and Paul P. Gardner
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Statistics and Probability ,Information Theory ,Information theory ,Machine learning ,computer.software_genre ,Biochemistry ,Measure (mathematics) ,Evolution, Molecular ,Structure-Activity Relationship ,Simple (abstract algebra) ,Sequence Homology, Nucleic Acid ,Molecular Biology ,Conserved Sequence ,Mathematics ,Structure (mathematical logic) ,Supplementary data ,business.industry ,Sequence Analysis, RNA ,Rank (computer programming) ,Genetic Variation ,Function (mathematics) ,Mutual information ,Computer Science Applications ,Computational Mathematics ,Computational Theory and Mathematics ,Nucleic Acid Conformation ,RNA ,Artificial intelligence ,Data mining ,business ,computer ,Sequence Alignment ,Algorithms - Abstract
Motivation: The importance of non-coding RNAs is becoming increasingly evident, and often the function of these molecules depends on the structure. It is common to use alignments of related RNA sequences to deduce the consensus secondary structure by detecting patterns of co-evolution. A central part of such an analysis is to measure covariation between two positions in an alignment. Here, we rank various measures ranging from simple mutual information to more advanced covariation measures. Results: Mutual information is still used for secondary structure prediction, but the results of this study indicate which measures are useful. Incorporating more structural information by considering e.g. indels and stacking improves accuracy, suggesting that physically realistic measures yield improved predictions. This can be used to improve both current and future programs for secondary structure prediction. The best measure tested is the RNAalifold covariation measure modified to include stacking. Availability: Scripts, data and supplementary material can be found at Contact: stinus@binf.ku.dk Supplementary information: Supplementary data are available at Bioinformatics online.
- Published
- 2006
26. Robust Identification of Noncoding RNA from Transcriptomes Requires Phylogenetically-Informed Sampling
- Author
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Alicia Sook-Wei Lai, Stinus Lindgreen, Sinan Uğur Umu, Anthony M. Poole, Nicholas R. Thomson, Wenting Liu, Hisham Eldai, Nicole E. Wheeler, Patrick J. Biggs, Paul P. Gardner, Stephanie McGimpsey, and Lars Barquist
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Evolutionary Genetics ,RNA, Untranslated ,RNA, Archaeal ,Genome ,Transcriptome ,Databases, Genetic ,Cluster Analysis ,Biology (General) ,Genome Evolution ,Phylogeny ,Genetics ,Bacterial Genomics ,Ecology ,Microbial Genetics ,Genomics ,Non-coding RNA ,RNA, Bacterial ,Computational Theory and Mathematics ,Modeling and Simulation ,Transcriptome Analysis ,Transcriptional noise ,Research Article ,Next-Generation Sequencing ,Genome evolution ,QH301-705.5 ,Microbial Genomics ,Computational biology ,Biology ,Microbiology ,Molecular Evolution ,Cellular and Molecular Neuroscience ,Phylogenetics ,medicine ,Quantitative Biology - Genomics ,ddc:610 ,Molecular Biology ,Gene ,Ecology, Evolution, Behavior and Systematics ,Genomics (q-bio.GN) ,Evolutionary Biology ,Bacteria ,Gene Expression Profiling ,Biology and Life Sciences ,Computational Biology ,Comparative Genomics ,Genome Analysis ,medicine.disease ,Genome Annotation ,Archaea ,FOS: Biological sciences ,Genome Expression Analysis - Abstract
Noncoding RNAs are integral to a wide range of biological processes, including translation, gene regulation, host-pathogen interactions and environmental sensing. While genomics is now a mature field, our capacity to identify noncoding RNA elements in bacterial and archaeal genomes is hampered by the difficulty of de novo identification. The emergence of new technologies for characterizing transcriptome outputs, notably RNA-seq, are improving noncoding RNA identification and expression quantification. However, a major challenge is to robustly distinguish functional outputs from transcriptional noise. To establish whether annotation of existing transcriptome data has effectively captured all functional outputs, we analysed over 400 publicly available RNA-seq datasets spanning 37 different Archaea and Bacteria. Using comparative tools, we identify close to a thousand highly-expressed candidate noncoding RNAs. However, our analyses reveal that capacity to identify noncoding RNA outputs is strongly dependent on phylogenetic sampling. Surprisingly, and in stark contrast to protein-coding genes, the phylogenetic window for effective use of comparative methods is perversely narrow: aggregating public datasets only produced one phylogenetic cluster where these tools could be used to robustly separate unannotated noncoding RNAs from a null hypothesis of transcriptional noise. Our results show that for the full potential of transcriptomics data to be realized, a change in experimental design is paramount: effective transcriptomics requires phylogeny-aware sampling., 16 pages, 5 figures
- Published
- 2014
27. Codon evolution: Mechanisms and Models
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Stinus Lindgreen
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Genetics ,Change over time ,education.field_of_study ,Protein structure ,Sequence analysis ,Genetic variation ,Population ,Computational biology ,Biology ,education ,Gene ,Ecology, Evolution, Behavior and Systematics - Abstract
The unifying principle in almost all of bioinformatics is sequence analysis: no matter if you are predicting the structure of proteins, analyzing the genetic variation in a population, or deciphering the evolutionary history of your favorite gene, your analysis hinges on looking at biological sequences and how they change over time, between species, or from gene to gene. Biological sequence analysis is the cornerstone.
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- 2012
28. Multiple alignment and structure prediction of non-coding RNA sequences
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Paul P. Gardner, Anders Krogh, and Stinus Lindgreen
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Sequence analysis ,Computer science ,Structural alignment ,Computational biology ,computer.software_genre ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,Structural Biology ,0101 mathematics ,Protein secondary structure ,Molecular Biology ,Alignment-free sequence analysis ,030304 developmental biology ,0303 health sciences ,Multiple sequence alignment ,Applied Mathematics ,RNA ,Non-coding RNA ,Computer Science Applications ,010101 applied mathematics ,Poster Presentation ,Data mining ,DNA microarray ,Heuristics ,computer - Abstract
Background As the importance of non-coding RNAs becomes more evident, the need for computational methods for ncRNAs grows. Predicting the secondary structure is of great importance, and combining this with multiple alignment yields a useful tool for researchers. The exact solution to the problem of simultaneous multiple alignment and structure prediction for RNA sequences was described by Sankoff [1], but to date only pairwise implementations (e.g. Foldalign [2], Dynalign [3]) or heuristics for multiple sequences (e.g. FoldalignM [4], LocARNA [5], RNA Sampler [6]) exist.
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29. Improving ancient DNA read mapping against modern reference genomes
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Anders Krogh, Ludovic Orlando, Khaled A. S. Al-Rasheid, John F. Thompson, Aurélien Ginolhac, Eske Willerslev, Mikkel Schubert, and Stinus Lindgreen
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0106 biological sciences ,Genotype ,lcsh:QH426-470 ,lcsh:Biotechnology ,Sequence assembly ,Genomics ,Computational biology ,Biology ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,lcsh:TP248.13-248.65 ,Genetics ,Humans ,Illumina dye sequencing ,030304 developmental biology ,Comparative genomics ,Whole genome sequencing ,0303 health sciences ,Fossils ,Shotgun sequencing ,Methodology Article ,High-Throughput Nucleotide Sequencing ,Sequence Analysis, DNA ,lcsh:Genetics ,Ancient DNA ,DNA Damage ,Personal genomics ,Biotechnology - Abstract
Background Next-Generation Sequencing has revolutionized our approach to ancient DNA (aDNA) research, by providing complete genomic sequences of ancient individuals and extinct species. However, the recovery of genetic material from long-dead organisms is still complicated by a number of issues, including post-mortem DNA damage and high levels of environmental contamination. Together with error profiles specific to the type of sequencing platforms used, these specificities could limit our ability to map sequencing reads against modern reference genomes and therefore limit our ability to identify endogenous ancient reads, reducing the efficiency of shotgun sequencing aDNA. Results In this study, we compare different computational methods for improving the accuracy and sensitivity of aDNA sequence identification, based on shotgun sequencing reads recovered from Pleistocene horse extracts using Illumina GAIIx and Helicos Heliscope platforms. We show that the performance of the Burrows Wheeler Aligner (BWA), that has been developed for mapping of undamaged sequencing reads using platforms with low rates of indel-types of sequencing errors, can be employed at acceptable run-times by modifying default parameters in a platform-specific manner. We also examine if trimming likely damaged positions at read ends can increase the recovery of genuine aDNA fragments and if accurate identification of human contamination can be achieved using a strategy previously suggested based on best hit filtering. We show that combining our different mapping and filtering approaches can increase the number of high-quality endogenous hits recovered by up to 33%. Conclusions We have shown that Illumina and Helicos sequences recovered from aDNA extracts could not be aligned to modern reference genomes with the same efficiency unless mapping parameters are optimized for the specific types of errors generated by these platforms and by post-mortem DNA damage. Our findings have important implications for future aDNA research, as we define mapping guidelines that improve our ability to identify genuine aDNA sequences, which in turn could improve the genotyping accuracy of ancient specimens. Our framework provides a significant improvement to the standard procedures used for characterizing ancient genomes, which is challenged by contamination and often low amounts of DNA material.
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