| 1. |
- Finn, Robert D, et al.
(författare)
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Pfam : clans, web tools and services.
- 2006
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Ingår i: Nucleic Acids Res. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 34:Database issue, s. D247-51
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Horie, Masafumi, et al.
(författare)
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Integrative CAGE and DNA Methylation Profiling Identify Epigenetically Regulated Genes in NSCLC
- 2017
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Ingår i: Molecular Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1541-7786 .- 1557-3125. ; 15:10, s. 1354-1365
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer is the leading cause of cancer-related deaths worldwide. The majority of cancer driver mutations have been identified; however, relevant epigenetic regulation involved in tumorigenesis has only been fragmentarily analyzed. Epigenetically regulated genes have a great theranostic potential, especially in tumors with no apparent driver mutations. Here, epigenetically regulated genes were identified in lung cancer by an integrative analysis of promoter-level expression profiles from Cap Analysis of Gene Expression (CAGE) of 16 nonsmall cell lung cancer (NSCLC) cell lines and 16 normal lung primary cell specimens with DNA methylation data of 69 NSCLC cell lines and 6 normal lung epithelial cells. A core set of 49 coding genes and 10 long noncoding RNAs (lncRNA), which are upregulated in NSCLC cell lines due to promoter hypomethylation, was uncovered. Twenty-two epigenetically regulated genes were validated (upregulated genes with hypomethylated promoters) in the adenocarcinoma and squamous cell cancer subtypes of lung cancer using The Cancer Genome Atlas data. Furthermore, it was demonstrated that multiple copies of the REP522 DNA repeat family are prominently upregulated due to hypomethylation in NSCLC cell lines, which leads to cancer-specific expression of lncRNAs, such as RP1-90G24.10, AL022344.4, and PCAT7. Finally, Myeloma Overexpressed (MYEOV) was identified as the most promising candidate. Functional studies demonstrated that MYEOV promotes cell proliferation, survival, and invasion. Moreover, high MYEOV expression levels were associated with poor prognosis. (C) 2017 AACR.
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| 3. |
- Horie, Masafumi, et al.
(författare)
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Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Periodontitis is affecting over half of the adult population, and represents a major public health problem. Previously, we isolated a subset of gingival fibroblasts (GFs) from periodontitis patients, designated as periodontitis-associated fibroblasts (PAFs), which were highly capable of collagen degradation. To elucidate their molecular profiles, GFs isolated form healthy and periodontitis-affected gingival tissues were analyzed by CAGE-seq and integrated with the FANTOM5 atlas. GFs from healthy gingival tissues displayed distinctive patterns of CAGE profiles as compared to fibroblasts from other organ sites and characterized by specific expression of developmentally important transcription factors such as BARX1, PAX9, LHX8, and DLX5. In addition, a novel long non-coding RNA associated with LHX8 was described. Furthermore, we identified DLX5 regulating expression of the long variant of RUNX2 transcript, which was specifically active in GFs but not in their periodontitis-affected counterparts. Knockdown of these factors in GFs resulted in altered expression of extracellular matrix (ECM) components. These results indicate activation of DLX5 and RUNX2 via its distal promoter represents a unique feature of GFs, and is important for ECM regulation. Down-regulation of these transcription factors in PAFs could be associated with their property to degrade collagen, which may impact on the process of periodontitis.
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| 4. |
- Lassmann, Timo
(författare)
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Algorithms for building and evaluating multiple sequence alignments
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The alignment of biological sequences is crucial for the transfer of annotation from model organisms to humans. Pairwise alignment of sequences can reveal homology while multiple alignments are used to characterize protein families and elucidate their evolutionary history. We developed several software packages to create, evaluate and visualize multiple alignments. Our alignment program Kalign combines excellent accuracy with unparalleled computational benefits. The initial publication outlines the algorithm and innovations introduced to the field, while the second introduced several key improvements and additions to the original algorithm. The accuracy of Kalign is high for both protein and nucleotide alignments and Kalign can thus be used for a wide range of applications in genomics, including homology detection, protein and RNA structure prediction, phylogenetic analysis and promoter prediction. The assessment of alignment quality is a tough problem the field. While alignment programs can be tested on benchmark sets to reveal their overall performance, determining the accuracy of individual alignments is next to impossible. We approached this problem by analyzing several alignments of the same sequences and applying a consensus principle: if different methods arrive at the same conclusion it is more likely to be correct than when methods disagree. Our program MUMSA can thus diagnose faulty alignments which is critical in high throughput genomics application. Both Kalign and Mumsa can be freely accessed at our website http://msa.cgb.ki.se which also features Kalignvu, a lightweight alignment viewer.
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| 5. |
- Lassmann, Timo, et al.
(författare)
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Automatic assessment of alignment quality.
- 2005
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Ingår i: Nucleic Acids Res. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 33:22, s. 7120-8
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Tidskriftsartikel (refereegranskat)
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| 6. |
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| 7. |
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| 8. |
- Lassmann, Timo, et al.
(författare)
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Kalign2 : high-performance multiple alignment of protein and nucleotide sequences allowing external features.
- 2009
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 37:3, s. 858-65
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Tidskriftsartikel (refereegranskat)abstract
- In the growing field of genomics, multiple alignment programs are confronted with ever increasing amounts of data. To address this growing issue we have dramatically improved the running time and memory requirement of Kalign, while maintaining its high alignment accuracy. Kalign version 2 also supports nucleotide alignment, and a newly introduced extension allows for external sequence annotation to be included into the alignment procedure. We demonstrate that Kalign2 is exceptionally fast and memory-efficient, permitting accurate alignment of very large numbers of sequences. The accuracy of Kalign2 compares well to the best methods in the case of protein alignments while its accuracy on nucleotide alignments is generally superior. In addition, we demonstrate the potential of using known or predicted sequence annotation to improve the alignment accuracy. Kalign2 is freely available for download from the Kalign web site (http://msa.sbc.su.se/).
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| 9. |
- Ravasi, Timothy, et al.
(författare)
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An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man
- 2010
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Ingår i: CELL. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 140:5, s. 744-752
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Tidskriftsartikel (refereegranskat)abstract
- Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.
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| 10. |
- Timmons, James A, et al.
(författare)
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Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages.
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:11, s. 4401-4406
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Tidskriftsartikel (refereegranskat)abstract
- Attainment of a brown adipocyte cell phenotype in white adipocytes, with their abundant mitochondria and increased energy expenditure potential, is a legitimate strategy for combating obesity. The unique transcriptional regulators of the primary brown adipocyte phenotype are unknown, limiting our ability to promote brown adipogenesis over white. In the present work, we used microarray analysis strategies to study primary preadipocytes, and we made the striking discovery that brown preadipocytes demonstrate a myogenic transcriptional signature, whereas both brown and white primary preadipocytes demonstrate signatures distinct from those found in immortalized adipogenic models. We found a plausible SIRT1-related transcriptional signature during brown adipocyte differentiation that may contribute to silencing the myogenic signature. In contrast to brown preadipocytes or skeletal muscle cells, white preadipocytes express Tcf21, a transcription factor that has been shown to suppress myogenesis and nuclear receptor activity. In addition, we identified a number of developmental genes that are differentially expressed between brown and white preadipocytes and that have recently been implicated in human obesity. The interlinkage between the myocyte and the brown preadipocyte confirms the distinct origin for brown versus white adipose tissue and also represents a plausible explanation as to why brown adipocytes ultimately specialize in lipid catabolism rather than storage, much like oxidative skeletal muscle tissue.
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