| 1. |
- Akhter, Shirin, et al.
(författare)
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Cone-setting in spruce is regulated by conserved elements of the age-dependent flowering pathway
- 2022
-
Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 236:5, s. 1951-1963
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Tidskriftsartikel (refereegranskat)abstract
- Reproductive phase change is well characterized in angiosperm model species, but less studied in gymnosperms. We utilize the early cone-setting acrocona mutant to study reproductive phase change in the conifer Picea abies (Norway spruce), a gymnosperm. The acrocona mutant frequently initiates cone-like structures, called transition shoots, in positions where wild-type P. abies always produces vegetative shoots. We collect acrocona and wild-type samples, and RNA-sequence their messenger RNA (mRNA) and microRNA (miRNA) fractions. We establish gene expression patterns and then use allele-specific transcript assembly to identify mutations in acrocona. We genotype a segregating population of inbred acrocona trees. A member of the SQUAMOSA BINDING PROTEIN-LIKE (SPL) gene family, PaSPL1, is active in reproductive meristems, whereas two putative negative regulators of PaSPL1, miRNA156 and the conifer specific miRNA529, are upregulated in vegetative and transition shoot meristems. We identify a mutation in a putative miRNA156/529 binding site of the acrocona PaSPL1 allele and show that the mutation renders the acrocona allele tolerant to these miRNAs. We show co-segregation between the early cone-setting phenotype and trees homozygous for the acrocona mutation. In conclusion, we demonstrate evolutionary conservation of the age-dependent flowering pathway and involvement of this pathway in regulating reproductive phase change in the conifer P. abies.
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| 2. |
- Akhter, Shirin, et al.
(författare)
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Integrative Analysis of Three RNA Sequencing Methods Identifies Mutually Exclusive Exons of MADS-Box Isoforms During Early Bud Development in Picea abies
- 2018
-
Ingår i: Frontiers in Plant Science. - : Frontiers Media S.A.. - 1664-462X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Recent efforts to sequence the genomes and transcriptomes of several gymnosperm species have revealed an increased complexity in certain gene families in gymnosperms as compared to angiosperms. One example of this is the gymnosperm sister Glade to angiosperm TM3-like MADS-box genes, which at least in the conifer lineage has expanded in number of genes. We have previously identified a member of this subclade, the conifer gene DEFICIENS AGAMOUS LIKE 19 (DAL19), as being specifically upregulated in cone-setting shoots. Here, we show through Sanger sequencing of mRNA-derived cDNA and mapping to assembled conifer genomic sequences that DAL19 produces six mature mRNA splice variants in Picea abies. These splice variants use alternate first and last exons, while their four central exons constitute a core region present in all six transcripts. Thus, they are likely to be transcript isoforms. Quantitative Real-Time PCR revealed that two mutually exclusive first DAL19 exons are differentially expressed across meristems that will form either male or female cones, or vegetative shoots. Furthermore, mRNA in situ hybridization revealed that two mutually exclusive last DAL19 exons were expressed in a cell-specific pattern within bud meristems. Based on these findings in DAL19, we developed a sensitive approach to transcript isoform assembly from short-read sequencing of mRNA. We applied this method to 42 putative MADS-box core regions in P abies, from which we assembled 1084 putative transcripts. We manually curated these transcripts to arrive at 933 assembled transcript isoforms of 38 putative MADS-box genes. 152 of these isoforms, which we assign to 28 putative MADS-box genes, were differentially expressed across eight female, male, and vegetative buds. We further provide evidence of the expression of 16 out of the 38 putative MADS-box genes by mapping PacBio Iso-Seq circular consensus reads derived from pooled sample sequencing to assembled transcripts. In summary, our analyses reveal the use of mutually exclusive exons of MADS-box gene isoforms during early bud development in P. abies, and we find that the large number of identified MADS-box transcripts in P. abies results not only from expansion of the gene family through gene duplication events but also from the generation of numerous splice variants.
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| 3. |
- Akhter, Shirin, et al.
(författare)
-
Transcriptome studies of the early cone-setting acrocona mutant provide evidence for a functional conservation of the age-dependent flowering pathway between angiosperms and gymnosperms.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- All seed plants go through a juvenile period before they initiate seed- and pollen-bearing organs and reproduce. Reproductive phase-change is well characterized in angiosperm model species, but much less well described in gymnosperms. Here, we utilize the early cone-setting acrocona mutant to study reproductive phase change in the conifer Picea abies; a representative of the gymnosperm lineage. The acrocona mutant frequently initiates cone-like structures, called transition shoots, in positions where wild-type P. abies always produces vegetative shoots. By sequence analysis of mRNA and microRNA transcripts, we demonstrate that orthologous components of the Age-dependent flowering pathway are active at the time of cone initiation. We show that a member of the SQUAMOSA BINDING PROTEIN-LIKE (SPL) gene family, PaSPL7, is active in reproductive meristems, whereas a putative negative regulator of PaSPL7, microRNA156 is upregulated in vegetative meristem. By allele-specific assembly, we also identify a short nucleotide polymorphism (SNP) in the miRNA156 binding of PaSPL7. By genotyping a segregating population of inbred acrocona trees, we show a clear co-segregation between the early cone-setting phenotype and trees homozygous for the SNP. Hence, the data presented demonstrate evolutionary conservation of the age-dependent flowering pathway and involvement of this pathway in regulating cone-setting in the conifer P. abies.
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| 4. |
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| 5. |
- Anderhag, Per, 1971-, et al.
(författare)
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Students' choice of post-compulsory science : In search of schools that compensate for the socio-economic background of their students
- 2013
-
Ingår i: International Journal of Science Education. - : Informa UK Limited. - 0950-0693 .- 1464-5289. ; 35:18, s. 3141-3160
-
Tidskriftsartikel (refereegranskat)abstract
- It is commonly argued that socio-economic inequalities can explain many of the differences in achievement and participation in science education that have been reported among countries and among schools within a country. We addressed this issue by examining (a) the relationship between variables associated with socio-economic background and application frequencies to the Swedish Natural Science Programme (NSP) in upper secondary school and (b) whether there are lower secondary schools in Sweden that seem to compensate for these variables. Data from Statistics Sweden (SCB) covering the whole population of 106,483 ninth-grade students were used to calculate the probability for each student to apply to the NSP. Our results indicate that the variables, such as parental educational level and grades, have explanatory power, but with varying effect for different subpopulations of students. For example, grades in mathematics have a greater impact than grades in science for females’ choice of the NSP. The opposite holds for male students. Out of 1,342 schools, 158 deviated significantly from predicted, that is, the students in these schools applied to the NSP in greater or lesser extent than expected. The number of deviating schools is greater than predicted by pure random variation. This suggests that variables of socio-economic background are only a partial explanation of the application frequencies, and that the deviation needs to be investigated further. Our findings suggest that in order to understand why schools deviate positively and so compensate for the socio-economic background of their students, we need to study their practices more closely
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| 6. |
- Armenteros, Jose Juan Almagro, et al.
(författare)
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Detecting sequence signals in targeting peptides using deep learning
- 2019
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Ingår i: Life Science Alliance. - : LIFE SCIENCE ALLIANCE LLC. - 2575-1077. ; 2:5
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Tidskriftsartikel (refereegranskat)abstract
- In bioinformatics, machine learning methods have been used to predict features embedded in the sequences. In contrast to what is generally assumed, machine learning approaches can also provide new insights into the underlying biology. Here, we demonstrate this by presenting TargetP 2.0, a novel state-of-the-art method to identify N-terminal sorting signals, which direct proteins to the secretory pathway, mitochondria, and chloroplasts or other plastids. By examining the strongest signals from the attention layer in the network, we find that the second residue in the protein, that is, the one following the initial methionine, has a strong influence on the classification. We observe that two-thirds of chloroplast and thylakoid transit peptides have an alanine in position 2, compared with 20% in other plant proteins. We also note that in fungi and single-celled eukaryotes, less than 30% of the targeting peptides have an amino acid that allows the removal of the N-terminal methionine compared with 60% for the proteins without targeting peptide. The importance of this feature for predictions has not been highlighted before.
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| 7. |
- Bertone, Paul, et al.
(författare)
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Design optimization methods for genomic DNA tiling arrays.
- 2006
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 16:2, s. 271-281
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Tidskriftsartikel (refereegranskat)abstract
- A recent development in microarray research entails the unbiased coverage, or tiling, of genomic DNA for the large-scale identification of transcribed sequences and regulatory elements. A central issue in designing tiling arrays is that of arriving at a single-copy tile path, as significant sequence cross-hybridization can result from the presence of non-unique probes on the array. Due to the fragmentation of genomic DNA caused by the widespread distribution of repetitive elements, the problem of obtaining adequate sequence coverage increases with the sizes of subsequence tiles that are to be included in the design. This becomes increasingly problematic when considering complex eukaryotic genomes that contain many thousands of interspersed repeats. The general problem of sequence tiling can be framed as finding an optimal partitioning of non-repetitive subsequences over a prescribed range of tile sizes, on a DNA sequence comprising repetitive and non-repetitive regions. Exact solutions to the tiling problem become computationally infeasible when applied to large genomes, but successive optimizations are developed that allow their practical implementation. These include an efficient method for determining the degree of similarity of many oligonucleotide sequences over large genomes, and two algorithms for finding an optimal tile path composed of longer sequence tiles. The first algorithm, a dynamic programming approach, finds an optimal tiling in linear time and space; the second applies a heuristic search to reduce the space complexity to a constant requirement. A Web resource has also been developed, accessible at http://tiling.gersteinlab.org, to generate optimal tile paths from user-provided DNA sequences.
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| 8. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 9. |
- Ebenhard, Torbjörn, et al.
(författare)
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Lågskogsbruk – biobränsleproduktion i samklang med miljömål
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Lågskogsbruk går ut på att återkommande hugga lövträd som slår skott från en gemensam stubb-bas eller sockel. Lågskogens två huvudtyper, skottskogar och hamlingsskogar, kan ses som halvnaturliga biotoper med lång historia och egna utvecklade organismsamhällen, däribland många naturvårdsintressanta arter, som ursprungligen levde i naturliga biotoper som inte längre existerar. Lågskogen erbjuder gamla strukturer och substrat utan att miljön blir kontinuerligt skuggig som i högskog. Det är både möjligt och önskvärt att bedriva ett modernt lågskogsbruk för biomassaproduktion, i synnerhet på marker som idag inte används för skogsbruk eller jordbruksproduktion. Vi bedömer att det finns totalt ca en halv miljon hektar av skyddade områden, restmarker i jordbrukslandskapet, ängs- och hagmarker, väg- och järnvägsområden, kraftledningsgator, samt tätortsnära parker och friluftsområden där lågskogsbruk skulle vara lämpligt. Med en produktion av 2-5 ton biomassa per hektar och år skulle detta kunna ge 10-24 MWh energi per hektar och år, sammanlagt för landet 5-12 TWh per år. Jämfört med de bästa biomassagrödorna (Salix, Miscanthus) har lågskogen inte samma potential som bränsleproducent, men den står sig väl mot raps. Lågskogen är dock mer effektiv än vanliga biomassagrödor med avseende på utsläpp av växthusgaser per producerad energienhet, snabbheten i återinlagring av kol, och gynnandet av biologisk mångfald.
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| 10. |
- Edsgärd, Daniel, et al.
(författare)
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GeneiASE : Detection of condition-dependent and static allele-specific expression from RNA-seq data without haplotype information
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Allele-specific expression (ASE) is the imbalance in transcription between maternal and paternal alleles at a locus and can be probed in single individuals using massively parallel DNA sequencing technology. Assessing ASE within a single sample provides a static picture of the ASE, but the magnitude of ASE for a given transcript may vary between different biological conditions in an individual. Such condition-dependent ASE could indicate a genetic variation with a functional role in the phenotypic difference. We investigated ASE through RNA-sequencing of primary white blood cells from eight human individuals before and after the controlled induction of an inflammatory response, and detected condition-dependent and static ASE at 211 and 13021 variants, respectively. We developed a method, GeneiASE, to detect genes exhibiting static or condition-dependent ASE in single individuals. GeneiASE performed consistently over a range of read depths and ASE effect sizes, and did not require phasing of variants to estimate haplotypes. We observed condition-dependent ASE related to the inflammatory response in 19 genes, and static ASE in 1389 genes. Allele-specific expression was confirmed by validation of variants through real-time quantitative RT-PCR, with RNA-seq and RT-PCR ASE effect-size correlations r = 0.67 and r = 0.94 for static and condition-dependent ASE, respectively.
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| 11. |
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| 12. |
- Emanuelsson, Olof, et al.
(författare)
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Assessing the performance of different high-density tiling microarray strategies for mapping transcribed regions of the human genome.
- 2007
-
Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 886-897
-
Tidskriftsartikel (refereegranskat)abstract
- Genomic tiling microarrays have become a popular tool for interrogating the transcriptional activity of large regions of the genome in an unbiased fashion. There are several key parameters associated with each tiling experiment (e.g., experimental protocols and genomic tiling density). Here, we assess the role of these parameters as they are manifest in different tiling-array platforms used for transcription mapping. First, we analyze how a number of published tiling-array experiments agree with established gene annotation on human chromosome 22. We observe that the transcription detected from high-density arrays correlates substantially better with annotation than that from other array types. Next, we analyze the transcription-mapping performance of the two main high-density oligonucleotide array platforms in the ENCODE regions of the human genome. We hybridize identical biological samples and develop several ways of scoring the arrays and segmenting the genome into transcribed and nontranscribed regions, with the aim of making the platforms most comparable to each other. Finally, we develop a platform comparison approach based on agreement with known annotation. Overall, we find that the performance improves with more data points per locus, coupled with statistical scoring approaches that properly take advantage of this, where this larger number of data points arises from higher genomic tiling density and the use of replicate arrays and mismatches. While we do find significant differences in the performance of the two high-density platforms, we also find that they complement each other to some extent. Finally, our experiments reveal a significant amount of novel transcription outside of known genes, and an appreciable sample of this was validated by independent experiments.
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| 13. |
- Emanuelsson, Olof, et al.
(författare)
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ChloroP, a neural network-based method for predicting chloroplast transit peptides and their cleavage sites.
- 1999
-
Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 8:5, s. 978-984
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Tidskriftsartikel (refereegranskat)abstract
- We present a neural network based method (ChloroP) for identifying chloroplast transit peptides and their cleavage sites. Using cross-validation, 88% of the sequences in our homology reduced training set were correctly classified as transit peptides or nontransit peptides. This performance level is well above that of the publicly available chloroplast localization predictor PSORT. Cleavage sites are predicted using a scoring matrix derived by an automatic motif-finding algorithm. Approximately 60% of the known cleavage sites in our sequence collection were predicted to within +/-2 residues from the cleavage sites given in SWISS-PROT. An analysis of 715 Arabidopsis thaliana sequences from SWISS-PROT suggests that the ChloroP method should be useful for the identification of putative transit peptides in genome-wide sequence data. The ChloroP predictor is available as a web-server at http://www.cbs.dtu.dk/services/ChloroP/.
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| 14. |
- Emanuelsson, Olof, et al.
(författare)
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Engagera och aktivera studenter med inspiration från konferenser : examination genom poster-presentation
- 2014
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Ingår i: Proceedings 2014, 8:e Pedagogiska inspirationskonferensen 17 december 2014. - Lund : Lund University.
-
Konferensbidrag (refereegranskat)abstract
- I en forskningsnära kurs om 7.5 hp på master-nivå inom bioinformatikämnet vid KTH består drygt halva kursen av ett projekt som genomförs i grupper om tre studenter. Varje projekt har en egen projektuppgift med inget eller marginellt överlapp med andra gruppers uppgifter. Projekten är så gott som uteslutande baserade på aktuella frågeställningar i lärarteamets egna forskningsgrupper eller deras närhet. Projektet redovisas dels genom en posterpresentation, dels med individuell webbaserad projektdagbok. Vid posterredovisningen, som omfattar tre timmar i slutet av tentamensperioden, är alla kursdeltagare med. Vi försöker i möjligaste mån efterlikna situationen där ett autentiskt forskningsresultat presenteras på en riktig konferens. Varje deltagare (student) förväntas alltså ta del av varje annan grupps poster, på samma sätt som sker vid de flesta vetenskapliga konferenser. Vi genomför en enklare kamratbedömning på posternivå, där varje student ska avge en kort och konfidentiell kommentar om var och en av övriga postrar. Kursens lärare bedömer förstås också postrarna. En av svårigheterna är att sätta individuella betyg. Här använder vi oss av individuella projektdagböcker, som ger vägledning till de olika individernas insatser inom projektet. Vi har provat detta under fyra kursomgångar med som mest sju projekt. Examinationsformen är rolig och motiverande både för studenterna och lärarna.
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| 15. |
- Emanuelsson, Olof, et al.
(författare)
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In silico prediction of the peroxisomal proteome in fungi, plants and animals.
- 2003
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Ingår i: Journal of Molecular Biology. - 0022-2836 .- 1089-8638. ; 330:2, s. 443-456
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Tidskriftsartikel (refereegranskat)abstract
- In an attempt to improve our abilities to predict peroxisomal proteins, we have combined machine-learning techniques for analyzing peroxisomal targeting signals (PTS1) with domain-based cross-species comparisons between eight eukaryotic genomes. Our results indicate that this combined approach has a significantly higher specificity than earlier attempts to predict peroxisomal localization, without a loss in sensitivity. This allowed us to predict 430 peroxisomal proteins that almost completely lack a localization annotation. These proteins can be grouped into 29 families covering most of the known steps in all known peroxisomal pathways. In general, plants have the highest number of predicted peroxisomal proteins, and fungi the smallest number.
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| 16. |
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| 17. |
- Emanuelsson, Olof, et al.
(författare)
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Locating proteins in the cell using TargetP, SignalP and related tools.
- 2007
-
Ingår i: Nature Protocols. - : Springer Science and Business Media LLC. - 1754-2189 .- 1750-2799. ; 2:4, s. 953-971
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Tidskriftsartikel (refereegranskat)abstract
- Determining the subcellular localization of a protein is an important first step toward understanding its function. Here, we describe the properties of three well-known N-terminal sequence motifs directing proteins to the secretory pathway, mitochondria and chloroplasts, and sketch a brief history of methods to predict subcellular localization based on these sorting signals and other sequence properties. We then outline how to use a number of internet-accessible tools to arrive at a reliable subcellular localization prediction for eukaryotic and prokaryotic proteins. In particular, we provide detailed step-by-step instructions for the coupled use of the amino-acid sequence-based predictors TargetP, SignalP, ChloroP and TMHMM, which are all hosted at the Center for Biological Sequence Analysis, Technical University of Denmark. In addition, we describe and provide web references to other useful subcellular localization predictors. Finally, we discuss predictive performance measures in general and the performance of TargetP and SignalP in particular.
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| 18. |
- Emanuelsson, Olof
(författare)
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Predicting protein subcellular localisation from amino acid sequence information.
- 2002
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Ingår i: Briefings in Bioinformatics. - 1467-5463 .- 1477-4054. ; 3:4, s. 361-76
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Tidskriftsartikel (refereegranskat)abstract
- Predicting the subcellular localisation of proteins is an important part of the elucidation of their functions and interactions. Here, the amino acid sequence motifs that direct proteins to their proper subcellular compartment are surveyed, different methods for localisation prediction are discussed, and some benchmarks for the more commonly used predictors are presented.
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| 19. |
- Emanuelsson, Olof, et al.
(författare)
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Predicting subcellular localization of proteins based on their N-terminal amino acid sequence.
- 2000
-
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 300:4, s. 1005-1016
-
Tidskriftsartikel (refereegranskat)abstract
- A neural network-based tool, TargetP, for large-scale subcellular location prediction of newly identified proteins has been developed. Using N-terminal sequence information only, it discriminates between proteins destined for the mitochondrion, the chloroplast, the secretory pathway, and "other" localizations with a success rate of 85% (plant) or 90% (non-plant) on redundancy-reduced test sets. From a TargetP analysis of the recently sequenced Arabidopsis thaliana chromosomes 2 and 4 and the Ensembl Homo sapiens protein set, we estimate that 10% of all plant proteins are mitochondrial and 14% chloroplastic, and that the abundance of secretory proteins, in both Arabidopsis and Homo, is around 10%. TargetP also predicts cleavage sites with levels of correctly predicted sites ranging from approximately 40% to 50% (chloroplastic and mitochondrial presequences) to above 70% (secretory signal peptides). TargetP is available as a web-server at http://www.cbs.dtu.dk/services/TargetP/.
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| 20. |
- Emanuelsson, Olof, et al.
(författare)
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Prediction of organellar targeting signals.
- 2001
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Ingår i: Biochimica et Biophysica Acta. Molecular Cell Research. - 0167-4889 .- 1879-2596. ; 1541:1-2, s. 114-119
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Tidskriftsartikel (refereegranskat)abstract
- The subcellular location of a protein is an important characteristic with functional implications, and hence the problem of predicting subcellular localization from the amino acid sequence has received a fair amount of attention from the bioinformatics community. This review attempts to summarize the present state of the art in the field.
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| 21. |
- Euskirchen, Ghia M, et al.
(författare)
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Mapping of transcription factor binding regions in mammalian cells by ChIP : comparison of array- and sequencing-based technologies.
- 2007
-
Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 898-909
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Tidskriftsartikel (refereegranskat)abstract
- Recent progress in mapping transcription factor (TF) binding regions can largely be credited to chromatin immunoprecipitation (ChIP) technologies. We compared strategies for mapping TF binding regions in mammalian cells using two different ChIP schemes: ChIP with DNA microarray analysis (ChIP-chip) and ChIP with DNA sequencing (ChIP-PET). We first investigated parameters central to obtaining robust ChIP-chip data sets by analyzing STAT1 targets in the ENCODE regions of the human genome, and then compared ChIP-chip to ChIP-PET. We devised methods for scoring and comparing results among various tiling arrays and examined parameters such as DNA microarray format, oligonucleotide length, hybridization conditions, and the use of competitor Cot-1 DNA. The best performance was achieved with high-density oligonucleotide arrays, oligonucleotides >/=50 bases (b), the presence of competitor Cot-1 DNA and hybridizations conducted in microfluidics stations. When target identification was evaluated as a function of array number, 80%-86% of targets were identified with three or more arrays. Comparison of ChIP-chip with ChIP-PET revealed strong agreement for the highest ranked targets with less overlap for the low ranked targets. With advantages and disadvantages unique to each approach, we found that ChIP-chip and ChIP-PET are frequently complementary in their relative abilities to detect STAT1 targets for the lower ranked targets; each method detected validated targets that were missed by the other method. The most comprehensive list of STAT1 binding regions is obtained by merging results from ChIP-chip and ChIP-sequencing. Overall, this study provides information for robust identification, scoring, and validation of TF targets using ChIP-based technologies.
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| 22. |
- Gerstein, Mark B, et al.
(författare)
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What is a gene, post-ENCODE? : History and updated definition
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 669-681
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Tidskriftsartikel (refereegranskat)abstract
- While sequencing of the human genome surprised us with how many protein-coding genes there are, it did not fundamentally change our perspective on what a gene is. In contrast, the complex patterns of dispersed regulation and pervasive transcription uncovered by the ENCODE project, together with non-genic conservation and the abundance of noncoding RNA genes, have challenged the notion of the gene. To illustrate this, we review the evolution of operational definitions of a gene over the past century--from the abstract elements of heredity of Mendel and Morgan to the present-day ORFs enumerated in the sequence databanks. We then summarize the current ENCODE findings and provide a computational metaphor for the complexity. Finally, we propose a tentative update to the definition of a gene: A gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products. Our definition side-steps the complexities of regulation and transcription by removing the former altogether from the definition and arguing that final, functional gene products (rather than intermediate transcripts) should be used to group together entities associated with a single gene. It also manifests how integral the concept of biological function is in defining genes.
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| 23. |
- Giota, Joanna, 1965, et al.
(författare)
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Special Education in Comprehensive Schools: Extent, Forms and Effects
- 2009
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Ingår i: Scandinavian Journal of Educational Research. ; 53:6, s. 557-578
-
Tidskriftsartikel (refereegranskat)abstract
- The present study aims to describe the extent and forms (integrated versus segregated) of special education support offered to pupils in comprehensive schools in Sweden over a period of 29 years and to study relations between support, background variables and goal attainment in Grade 9. The study is based on about 35,000 children born in 1972, 1977, 1982, and 1987, participating in the ongoing longitudinal project “Evaluation Through Follow-Up”. The findings reveal that boys and pupils from lower educational home-backgrounds and with non-Swedish backgrounds are over-represented among the groups that have received special education support. The findings also suggest that pupils who have received support, in general, tend to achieve educational goals in core curriculum subjects to a lesser extent than those who have never had any kind of support.
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| 24. |
- Höiom, Veronica, et al.
(författare)
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Hereditary uveal melanoma : A report of a germline mutation in BAP1
- 2013
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 52:4, s. 378-384
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Tidskriftsartikel (refereegranskat)abstract
- Melanoma of the eye is a rare and distinct subtype of melanoma, which only rarely are familial. However, cases of uveal melanoma (UM) have been found in families with mixed cancer syndromes. Here, we describe a comprehensive search for inherited genetic variation in a family with multiple cases of UM but no aggregation of other cancer diagnoses. The proband is a woman diagnosed with UM at 16 years who within 6 months developed liver metastases. We also identified two older paternal relatives of the proband who had died from UM. We performed exome sequencing of germline DNA from members of the affected family. Exome-wide analysis identified a novel loss-of-function mutation in the BAP1 gene, previously suggested as a tumor suppressor. The mutation segregated with the UM phenotype in this family, and we detected a loss of the wild-type allele in the UM tumor of the proband, strongly supporting a causative association with UM. Screening of BAP1 germline mutations in families predisposed for UM may be used to identify individuals at increased risk of disease. Such individuals may then be enrolled in preventive programs and regular screenings to facilitate early detection and thereby improve prognosis.
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| 25. |
- Iglesias, Maria Jesus, et al.
(författare)
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Combined Chromatin and Expression Analysis Reveals Specific Regulatory Mechanisms within Cytokine Genes in the Macrophage Early Immune Response
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2, s. e32306-
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS). To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches - gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of upregulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the chromatin level for specific genes and this study highlights the level of fine-tuning that occurs in the immune response.
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