-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Bacterial Infection Drives the Expression Dynamics of microRNAs and Their isomiRs
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate important cellular processes by inhibiting the expression of gene targets. In recent years, it has become clear that miRNAs play a critical role in the regulation of the immune response to infection, a highly complex phenotype involving the activation of both generic and infection-specific responses. However, it remains unclear to what extent miRNAs are involved in the regulation of these two types of response. Here, focusing on the miRNA response to mycobacteria, pathogens of major public health importance, we present the first comparative, deep sequencing-based analysis of the miRNA response to a panel of bacterial infections. We define a set of miRNAs that play an essential role in basic cellular responses to stress and identify pathogen-specific miRNA responses that reflect mechanisms by which certain pathogens interfere with the host response to infection. In addition, we show that infection can alter the expression level and proportions of miRNA isoforms, transcripts originating from the same miRNA but with slight differences in their nucleotide sequences. This study highlights a novel aspect of miRNA expression dynamics upon infection and increases our understanding of miRNA-mediated mechanisms involved in host cellular responses to infection.
Vyšlo v časopise: Bacterial Infection Drives the Expression Dynamics of microRNAs and Their isomiRs. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005064
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005064Souhrn
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate important cellular processes by inhibiting the expression of gene targets. In recent years, it has become clear that miRNAs play a critical role in the regulation of the immune response to infection, a highly complex phenotype involving the activation of both generic and infection-specific responses. However, it remains unclear to what extent miRNAs are involved in the regulation of these two types of response. Here, focusing on the miRNA response to mycobacteria, pathogens of major public health importance, we present the first comparative, deep sequencing-based analysis of the miRNA response to a panel of bacterial infections. We define a set of miRNAs that play an essential role in basic cellular responses to stress and identify pathogen-specific miRNA responses that reflect mechanisms by which certain pathogens interfere with the host response to infection. In addition, we show that infection can alter the expression level and proportions of miRNA isoforms, transcripts originating from the same miRNA but with slight differences in their nucleotide sequences. This study highlights a novel aspect of miRNA expression dynamics upon infection and increases our understanding of miRNA-mediated mechanisms involved in host cellular responses to infection.
Zdroje
1. Chaussabel D, Semnani RT, McDowell MA, Sacks D, Sher A, et al. Unique gene expression profiles of human macrophages and dendritic cells to phylogenetically distinct parasites. Blood 2003;102 : 672–681. 12663451
2. Huang Q, Liu D, Majewski P, Schulte LC, Korn JM, et al. The plasticity of dendritic cell responses to pathogens and their components. Science 2001;294 : 870–875. 11679675
3. Chevrier N, Mertins P, Artyomov MN, Shalek AK, Iannacone M, et al. Systematic discovery of TLR signaling components delineates viral-sensing circuits. Cell 2011;147 : 853–867. doi: 10.1016/j.cell.2011.10.022 22078882
4. Fairfax BP, Humburg P, Makino S, Naranbhai V, Wong D, et al. Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science 2014;343 : 1246949. doi: 10.1126/science.1246949 24604202
5. Gat-Viks I, Chevrier N, Wilentzik R, Eisenhaure T, Raychowdhury R, et al. Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli. Nat Biotechnol 2013;31 : 342–349. doi: 10.1038/nbt.2519 23503680
6. Lee MN, Ye C, Villani AC, Raj T, Li W, et al. Common genetic variants modulate pathogen-sensing responses in human dendritic cells. Science 2014;343 : 1246980. doi: 10.1126/science.1246980 24604203
7. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116 : 281–297. 14744438
8. Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet 2011;12 : 99–110. doi: 10.1038/nrg2936 21245828
9. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009;19 : 92–105. doi: 10.1101/gr.082701.108 18955434
10. Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science 2004;303 : 83–86. 14657504
11. Johnnidis JB, Harris MH, Wheeler RT, Stehling-Sun S, Lam MH, et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 2008;451 : 1125–1129. doi: 10.1038/nature06607 18278031
12. O'Connell RM, Rao DS, Baltimore D. microRNA regulation of inflammatory responses. Annu Rev Immunol 2012;30 : 295–312. doi: 10.1146/annurev-immunol-020711-075013 22224773
13. Lodish HF, Zhou B, Liu G, Chen CZ. Micromanagement of the immune system by microRNAs. Nat Rev Immunol 2008;8 : 120–130. doi: 10.1038/nri2252 18204468
14. O'Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol 2010;10 : 111–122. doi: 10.1038/nri2708 20098459
15. Cullen BR. Viruses and microRNAs: RISCy interactions with serious consequences. Genes Dev 2011;25 : 1881–1894. doi: 10.1101/gad.17352611 21896651
16. Eulalio A, Schulte L, Vogel J. The mammalian microRNA response to bacterial infections. RNA Biol 2012;9 : 742–750. doi: 10.4161/rna.20018 22664920
17. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 2006;6 : 857–866. 17060945
18. Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 2009;10 : 704–714. doi: 10.1038/nrg2634 19763153
19. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 2009;11 : 228–234. doi: 10.1038/ncb0309-228 19255566
20. Yang JS, Lai EC. Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants. Mol Cell 2011;43 : 892–903. doi: 10.1016/j.molcel.2011.07.024 21925378
21. Creighton CJ, Reid JG, Gunaratne PH. Expression profiling of microRNAs by deep sequencing. Brief Bioinform 2009;10 : 490–497. doi: 10.1093/bib/bbp019 19332473
22. Griffiths-Jones S, Hui JH, Marco A, Ronshaugen M. MicroRNA evolution by arm switching. EMBO Rep 2011;12 : 172–177. doi: 10.1038/embor.2010.191 21212805
23. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010;11 : 597–610. doi: 10.1038/nrg2843 20661255
24. Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs exhibit strand bias. Cell 2003;115 : 209–216. 14567918
25. Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, et al. Asymmetry in the assembly of the RNAi enzyme complex. Cell 2003;115 : 199–208. 14567917
26. Chang HT, Li SC, Ho MR, Pan HW, Ger LP, et al. Comprehensive analysis of microRNAs in breast cancer. BMC Genomics 2012;13 Suppl 7: S18. doi: 10.1186/1471-2164-13-S7-S18 23281739
27. Chiang HR, Schoenfeld LW, Ruby JG, Auyeung VC, Spies N, et al. Mammalian microRNAs: experimental evaluation of novel and previously annotated genes. Genes Dev 2010;24 : 992–1009. doi: 10.1101/gad.1884710 20413612
28. Cloonan N, Wani S, Xu Q, Gu J, Lea K, et al. MicroRNAs and their isomiRs function cooperatively to target common biological pathways. Genome Biol 2011;12: R126. doi: 10.1186/gb-2011-12-12-r126 22208850
29. Jagadeeswaran G, Zheng Y, Sumathipala N, Jiang H, Arrese EL, et al. Deep sequencing of small RNA libraries reveals dynamic regulation of conserved and novel microRNAs and microRNA-stars during silkworm development. BMC Genomics 2010;11 : 52. doi: 10.1186/1471-2164-11-52 20089182
30. Li SC, Liao YL, Ho MR, Tsai KW, Lai CH, et al. miRNA arm selection and isomiR distribution in gastric cancer. BMC Genomics 2012;13 Suppl 1: S13. doi: 10.1186/1471-2164-13-S1-S13 22369582
31. Marco A, Hui JH, Ronshaugen M, Griffiths-Jones S. Functional shifts in insect microRNA evolution. Genome Biol Evol 2010;2 : 686–696. doi: 10.1093/gbe/evq053 20817720
32. Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol 2013;14 : 475–488. doi: 10.1038/nrm3611 23800994
33. Glazov EA, Cottee PA, Barris WC, Moore RJ, Dalrymple BP, et al. A microRNA catalog of the developing chicken embryo identified by a deep sequencing approach. Genome Res 2008;18 : 957–964. doi: 10.1101/gr.074740.107 18469162
34. Morin RD, O'Connor MD, Griffith M, Kuchenbauer F, Delaney A, et al. Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. Genome Res 2008;18 : 610–621. doi: 10.1101/gr.7179508 18285502
35. Fernandez-Valverde SL, Taft RJ, Mattick JS. Dynamic isomiR regulation in Drosophila development. RNA 2010;16 : 1881–1888. doi: 10.1261/rna.2379610 20805289
36. Lee LW, Zhang S, Etheridge A, Ma L, Martin D, et al. Complexity of the microRNA repertoire revealed by next-generation sequencing. RNA 2010;16 : 2170–2180. doi: 10.1261/rna.2225110 20876832
37. Humphreys DT, Hynes CJ, Patel HR, Wei GH, Cannon L, et al. Complexity of murine cardiomyocyte miRNA biogenesis, sequence variant expression and function. PLoS One 2012;7: e30933. doi: 10.1371/journal.pone.0030933 22319597
38. Llorens F, Hummel M, Pantano L, Pastor X, Vivancos A, et al. Microarray and deep sequencing cross-platform analysis of the mirRNome and isomiR variation in response to epidermal growth factor. BMC Genomics 2013;14 : 371. doi: 10.1186/1471-2164-14-371 23724959
39. Marti E, Pantano L, Banez-Coronel M, Llorens F, Minones-Moyano E, et al. A myriad of miRNA variants in control and Huntington's disease brain regions detected by massively parallel sequencing. Nucleic Acids Res 2010;38 : 7219–7235. doi: 10.1093/nar/gkq575 20591823
40. Vaz C, Ahmad HM, Bharti R, Pandey P, Kumar L, et al. Analysis of the microRNA transcriptome and expression of different isomiRs in human peripheral blood mononuclear cells. BMC Res Notes 2013;6 : 390. doi: 10.1186/1756-0500-6-390 24073671
41. Zhou H, Arcila ML, Li Z, Lee EJ, Henzler C, et al. Deep annotation of mouse iso-miR and iso-moR variation. Nucleic Acids Res 2012;40 : 5864–5875. doi: 10.1093/nar/gks247 22434881
42. WHO (2013) Global Tuberculosis Report 2013. World Health Organization, Geneva.
43. Fu Y, Yi Z, Wu X, Li J, Xu F. Circulating microRNAs in patients with active pulmonary tuberculosis. J Clin Microbiol 2011;49 : 4246–4251. doi: 10.1128/JCM.05459-11 21998423
44. Kumar R, Halder P, Sahu SK, Kumar M, Kumari M, et al. Identification of a novel role of ESAT-6-dependent miR-155 induction during infection of macrophages with Mycobacterium tuberculosis. Cell Microbiol 2012;14 : 1620–1631. doi: 10.1111/j.1462-5822.2012.01827.x 22712528
45. Liu Y, Wang X, Jiang J, Cao Z, Yang B, et al. Modulation of T cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis. Mol Immunol 2011;48 : 1084–1090. doi: 10.1016/j.molimm.2011.02.001 21367459
46. Ma F, Xu S, Liu X, Zhang Q, Xu X, et al. The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-gamma. Nat Immunol 2011;12 : 861–869. doi: 10.1038/ni.2073 21785411
47. Maertzdorf J, Weiner J 3rd, Mollenkopf HJ, Bauer T, Prasse A, et al. Common patterns and disease-related signatures in tuberculosis and sarcoidosis. Proc Natl Acad Sci U S A 2012;109 : 7853–7858. doi: 10.1073/pnas.1121072109 22547807
48. Rajaram MV, Ni B, Morris JD, Brooks MN, Carlson TK, et al. Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b. Proc Natl Acad Sci U S A 2011;108 : 17408–17413. doi: 10.1073/pnas.1112660108 21969554
49. Sharbati J, Lewin A, Kutz-Lohroff B, Kamal E, Einspanier R, et al. Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon Mycobacterium avium subsp. hominissuis infection. PLoS One 2011;6: e20258. doi: 10.1371/journal.pone.0020258 21629653
50. Singh Y, Kaul V, Mehra A, Chatterjee S, Tousif S, et al. Mycobacterium tuberculosis controls microRNA-99b (miR-99b) expression in infected murine dendritic cells to modulate host immunity. J Biol Chem 2013;288 : 5056–5061. doi: 10.1074/jbc.C112.439778 23233675
51. Spinelli SV, Diaz A, D'Attilio L, Marchesini MM, Bogue C, et al. Altered microRNA expression levels in mononuclear cells of patients with pulmonary and pleural tuberculosis and their relation with components of the immune response. Mol Immunol 2013;53 : 265–269. doi: 10.1016/j.molimm.2012.08.008 22964481
52. Wang C, Yang S, Sun G, Tang X, Lu S, et al. Comparative miRNA expression profiles in individuals with latent and active tuberculosis. PLoS One 2011;6: e25832. doi: 10.1371/journal.pone.0025832 22003408
53. Wu J, Lu C, Diao N, Zhang S, Wang S, et al. Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study. Hum Immunol 2012;73 : 31–37. doi: 10.1016/j.humimm.2011.10.003 22037148
54. Yi Z, Fu Y, Ji R, Li R, Guan Z. Altered microRNA signatures in sputum of patients with active pulmonary tuberculosis. PLoS One 2012;7: e43184. doi: 10.1371/journal.pone.0043184 22900099
55. Siddle KJ, Deschamps M, Tailleux L, Nedelec Y, Pothlichet J, et al. A genomic portrait of the genetic architecture and regulatory impact of microRNA expression in response to infection. Genome Res 2014;24 : 850–859. doi: 10.1101/gr.161471.113 24482540
56. Friedlander MR, Mackowiak SD, Li N, Chen W, Rajewsky N. miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades. Nucleic Acids Res 2012;40 : 37–52. doi: 10.1093/nar/gkr688 21911355
57. Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol 2010;11: R106. doi: 10.1186/gb-2010-11-10-r106 20979621
58. Ernst J, Bar-Joseph Z. STEM: a tool for the analysis of short time series gene expression data. BMC Bioinformatics 2006;7 : 191. 16597342
59. Ernst J, Nau GJ, Bar-Joseph Z. Clustering short time series gene expression data. Bioinformatics 2005;21 Suppl 1: i159–168. 15961453
60. Yang JH, Li JH, Shao P, Zhou H, Chen YQ, et al. starBase: a database for exploring microRNA-mRNA interaction maps from Argonaute CLIP-Seq and Degradome-Seq data. Nucleic Acids Res 2011;39: D202–209. doi: 10.1093/nar/gkq1056 21037263
61. Langfelder P, Zhang B, Horvath S. Defining clusters from a hierarchical cluster tree: the Dynamic Tree Cut package for R. Bioinformatics 2008;24 : 719–720. 18024473
62. Yang JH, Li JH, Jiang S, Zhou H, Qu LH. ChIPBase: a database for decoding the transcriptional regulation of long non-coding RNA and microRNA genes from ChIP-Seq data. Nucleic Acids Res 2013;41: D177–187. doi: 10.1093/nar/gks1060 23161675
63. Barreiro LB, Tailleux L, Pai AA, Gicquel B, Marioni JC, et al. Deciphering the genetic architecture of variation in the immune response to Mycobacterium tuberculosis infection. Proc Natl Acad Sci U S A 2012;109 : 1204–1209. doi: 10.1073/pnas.1115761109 22233810
64. Viboud GI, Bliska JB. Yersinia outer proteins: role in modulation of host cell signaling responses and pathogenesis. Annu Rev Microbiol 2005;59 : 69–89. 15847602
65. Nahid MA, Yao B, Dominguez-Gutierrez PR, Kesavalu L, Satoh M, et al. Regulation of TLR2-mediated tolerance and cross-tolerance through IRAK4 modulation by miR-132 and miR-212. J Immunol 2013;190 : 1250–1263. doi: 10.4049/jimmunol.1103060 23264652
66. Pym AS, Brodin P, Brosch R, Huerre M, Cole ST. Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti. Mol Microbiol 2002;46 : 709–717. 12410828
67. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005;120 : 15–20. 15652477
68. Bueno MJ, Perez de Castro I, Malumbres M. Control of cell proliferation pathways by microRNAs. Cell Cycle 2008;7 : 3143–3148. 18843198
69. Galindo CL, Rosenzweig JA, Kirtley ML, Chopra AK. Pathogenesis of Y. enterocolitica and Y. pseudotuberculosis in Human Yersiniosis. J Pathog 2011;2011 : 182051. doi: 10.4061/2011/182051 22567322
70. van Kooyk Y, Geijtenbeek TB. DC-SIGN: escape mechanism for pathogens. Nat Rev Immunol 2003;3 : 697–709. 12949494
71. Jenner RG, Young RA. Insights into host responses against pathogens from transcriptional profiling. Nat Rev Microbiol 2005;3 : 281–294. 15806094
72. Amit I, Garber M, Chevrier N, Leite AP, Donner Y, et al. Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses. Science 2009;326 : 257–263. doi: 10.1126/science.1179050 19729616
73. He X, Jing Z, Cheng G. MicroRNAs: new regulators of Toll-like receptor signalling pathways. Biomed Res Int 2014;2014 : 945169. doi: 10.1155/2014/945169 24772440
74. O'Neill LA, Sheedy FJ, McCoy CE. MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat Rev Immunol 2011;11 : 163–175. doi: 10.1038/nri2957 21331081
75. Chen CZ, Schaffert S, Fragoso R, Loh C. Regulation of immune responses and tolerance: the microRNA perspective. Immunol Rev 2013;253 : 112–128. doi: 10.1111/imr.12060 23550642
76. Li Y, Shi X. MicroRNAs in the regulation of TLR and RIG-I pathways. Cell Mol Immunol 2013;10 : 65–71. doi: 10.1038/cmi.2012.55 23262976
77. Alexiou P, Maragkakis M, Papadopoulos GL, Reczko M, Hatzigeorgiou AG. Lost in translation: an assessment and perspective for computational microRNA target identification. Bioinformatics 2009;25 : 3049–3055. doi: 10.1093/bioinformatics/btp565 19789267
78. Martinez-Sanchez A, Murphy CL. MicroRNA Target Identification-Experimental Approaches. Biology (Basel) 2013;2 : 189–205. doi: 10.3390/biology2010189 24832658
79. Frigui W, Bottai D, Majlessi L, Monot M, Josselin E, et al. Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP. PLoS Pathog 2008;4: e33. doi: 10.1371/journal.ppat.0040033 18282096
80. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 2006;103 : 12481–12486. 16885212
81. Portevin D, Gagneux S, Comas I, Young D. Human macrophage responses to clinical isolates from the Mycobacterium tuberculosis complex discriminate between ancient and modern lineages. PLoS Pathog 2011;7: e1001307. doi: 10.1371/journal.ppat.1001307 21408618
82. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell 2003;115 : 787–798. 14697198
83. Burroughs AM, Ando Y, de Hoon MJ, Tomaru Y, Nishibu T, et al. A comprehensive survey of 3' animal miRNA modification events and a possible role for 3' adenylation in modulating miRNA targeting effectiveness. Genome Res 2010;20 : 1398–1410. doi: 10.1101/gr.106054.110 20719920
84. Neilsen CT, Goodall GJ, Bracken CP. IsomiRs—the overlooked repertoire in the dynamic microRNAome. Trends Genet 2012;28 : 544–549. doi: 10.1016/j.tig.2012.07.005 22883467
85. Jones MR, Quinton LJ, Blahna MT, Neilson JR, Fu S, et al. Zcchc11-dependent uridylation of microRNA directs cytokine expression. Nat Cell Biol 2009;11 : 1157–1163. doi: 10.1038/ncb1931 19701194
86. Katoh T, Sakaguchi Y, Miyauchi K, Suzuki T, Kashiwabara S, et al. Selective stabilization of mammalian microRNAs by 3' adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Genes Dev 2009;23 : 433–438. doi: 10.1101/gad.1761509 19240131
87. Backes S, Shapiro JS, Sabin LR, Pham AM, Reyes I, et al. Degradation of host microRNAs by poxvirus poly(A) polymerase reveals terminal RNA methylation as a protective antiviral mechanism. Cell Host Microbe 2012;12 : 200–210. doi: 10.1016/j.chom.2012.05.019 22901540
88. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009;136 : 215–233. doi: 10.1016/j.cell.2009.01.002 19167326
89. Morgan M, Anders S, Lawrence M, Aboyoun P, Pages H, et al. ShortRead: a bioconductor package for input, quality assessment and exploration of high-throughput sequence data. Bioinformatics 2009;25 : 2607–2608. doi: 10.1093/bioinformatics/btp450 19654119
90. Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 2009;10: R25. doi: 10.1186/gb-2009-10-3-r25 19261174
91. de Hoon MJ, Taft RJ, Hashimoto T, Kanamori-Katayama M, Kawaji H, et al. Cross-mapping and the identification of editing sites in mature microRNAs in high-throughput sequencing libraries. Genome Res 2010;20 : 257–264. doi: 10.1101/gr.095273.109 20051556
92. Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 2010;26 : 841–842. doi: 10.1093/bioinformatics/btq033 20110278
93. Fournier D, Skaug H, Ancheta J, Ianelli J, Magnusson A, et al. AD Model Builder: using automatic differentiation for statistical inference of highly parameterized complex nonlinear models. Optimization Methods and Software 2012;27 : 233–249.
94. Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, et al. An integrated map of genetic variation from 1,092 human genomes. Nature 2012;491 : 56–65. doi: 10.1038/nature11632 23128226
95. Excoffier L, Smouse PE, Quattro JM. Analysis of molecular variance inferred from metric distances among DNA haplotypes: application to human mitochondrial DNA restriction data. Genetics 1992;131 : 479–491. 1644282
96. Weir CL, Cockerham CC. Estimating F-statistics for the analysis of population structure. Evolution 1984;38 : 1358–1370.
97. Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, et al. Global variation in copy number in the human genome. Nature 2006;444 : 444–454. 17122850
98. Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, et al. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 2007;27 : 91–105. 17612493
99. Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 2008;9 : 559. doi: 10.1186/1471-2105-9-559 19114008
100. Langfelder P, Horvath S. Fast R Functions for Robust Correlations and Hierarchical Clustering. J Stat Softw 2012;46. 23050260
101. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001;25 : 402–408. 11846609
Štítky
Genetika Reprodukčná medicína
Článek NLRC5 Exclusively Transactivates MHC Class I and Related Genes through a Distinctive SXY ModuleČlánek Inhibition of Telomere Recombination by Inactivation of KEOPS Subunit Cgi121 Promotes Cell LongevityČlánek HOMER2, a Stereociliary Scaffolding Protein, Is Essential for Normal Hearing in Humans and MiceČlánek LRGUK-1 Is Required for Basal Body and Manchette Function during Spermatogenesis and Male FertilityČlánek The GATA Factor Regulates . Developmental Timing by Promoting Expression of the Family MicroRNAsČlánek Systems Biology of Tissue-Specific Response to Reveals Differentiated Apoptosis in the Tick VectorČlánek Phenotype Specific Analyses Reveal Distinct Regulatory Mechanism for Chronically Activated p53Článek The Nuclear Receptor DAF-12 Regulates Nutrient Metabolism and Reproductive Growth in NematodesČlánek The ATM Signaling Cascade Promotes Recombination-Dependent Pachytene Arrest in Mouse SpermatocytesČlánek The Small Protein MntS and Exporter MntP Optimize the Intracellular Concentration of Manganese
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2015 Číslo 3- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
-
Všetky články tohto čísla
- NLRC5 Exclusively Transactivates MHC Class I and Related Genes through a Distinctive SXY Module
- Licensing of Primordial Germ Cells for Gametogenesis Depends on Genital Ridge Signaling
- A Genomic Duplication is Associated with Ectopic Eomesodermin Expression in the Embryonic Chicken Comb and Two Duplex-comb Phenotypes
- Genome-wide Association Study and Meta-Analysis Identify as Genome-wide Significant Susceptibility Gene for Bladder Exstrophy
- Mutations of Human , Encoding the Mitochondrial Asparaginyl-tRNA Synthetase, Cause Nonsyndromic Deafness and Leigh Syndrome
- Exome Sequencing in an Admixed Isolated Population Indicates Variants Confer a Risk for Specific Language Impairment
- Genome-Wide Association Studies in Dogs and Humans Identify as a Risk Variant for Cleft Lip and Palate
- Rapid Evolution of Recombinant for Xylose Fermentation through Formation of Extra-chromosomal Circular DNA
- The Ribosome Biogenesis Factor Nol11 Is Required for Optimal rDNA Transcription and Craniofacial Development in
- Methyl Farnesoate Plays a Dual Role in Regulating Metamorphosis
- Maternal Co-ordinate Gene Regulation and Axis Polarity in the Scuttle Fly
- Maternal Filaggrin Mutations Increase the Risk of Atopic Dermatitis in Children: An Effect Independent of Mutation Inheritance
- Inhibition of Telomere Recombination by Inactivation of KEOPS Subunit Cgi121 Promotes Cell Longevity
- Clonality and Evolutionary History of Rhabdomyosarcoma
- HOMER2, a Stereociliary Scaffolding Protein, Is Essential for Normal Hearing in Humans and Mice
- Methylation-Sensitive Expression of a DNA Demethylase Gene Serves As an Epigenetic Rheostat
- BREVIPEDICELLUS Interacts with the SWI2/SNF2 Chromatin Remodeling ATPase BRAHMA to Regulate and Expression in Control of Inflorescence Architecture
- Seizures Are Regulated by Ubiquitin-specific Peptidase 9 X-linked (USP9X), a De-Ubiquitinase
- The Fun30 Chromatin Remodeler Fft3 Controls Nuclear Organization and Chromatin Structure of Insulators and Subtelomeres in Fission Yeast
- A Cascade of Iron-Containing Proteins Governs the Genetic Iron Starvation Response to Promote Iron Uptake and Inhibit Iron Storage in Fission Yeast
- Mutation in MRPS34 Compromises Protein Synthesis and Causes Mitochondrial Dysfunction
- LRGUK-1 Is Required for Basal Body and Manchette Function during Spermatogenesis and Male Fertility
- Cis-Regulatory Mechanisms for Robust Olfactory Sensory Neuron Class-restricted Odorant Receptor Gene Expression in
- Effects on Murine Behavior and Lifespan of Selectively Decreasing Expression of Mutant Huntingtin Allele by Supt4h Knockdown
- HDAC4-Myogenin Axis As an Important Marker of HD-Related Skeletal Muscle Atrophy
- A Conserved Domain in the Scc3 Subunit of Cohesin Mediates the Interaction with Both Mcd1 and the Cohesin Loader Complex
- Selective and Genetic Constraints on Pneumococcal Serotype Switching
- Bacterial Infection Drives the Expression Dynamics of microRNAs and Their isomiRs
- The GATA Factor Regulates . Developmental Timing by Promoting Expression of the Family MicroRNAs
- Accumulation of Glucosylceramide in the Absence of the Beta-Glucosidase GBA2 Alters Cytoskeletal Dynamics
- Reproductive Isolation of Hybrid Populations Driven by Genetic Incompatibilities
- The Contribution of Alu Elements to Mutagenic DNA Double-Strand Break Repair
- Systems Biology of Tissue-Specific Response to Reveals Differentiated Apoptosis in the Tick Vector
- Tfap2a Promotes Specification and Maturation of Neurons in the Inner Ear through Modulation of Bmp, Fgf and Notch Signaling
- The Lysine Acetyltransferase Activator Brpf1 Governs Dentate Gyrus Development through Neural Stem Cells and Progenitors
- PHABULOSA Controls the Quiescent Center-Independent Root Meristem Activities in
- DNA Polymerase ζ-Dependent Lesion Bypass in Is Accompanied by Error-Prone Copying of Long Stretches of Adjacent DNA
- Examining the Evolution of the Regulatory Circuit Controlling Secondary Metabolism and Development in the Fungal Genus
- Zinc Finger Independent Genome-Wide Binding of Sp2 Potentiates Recruitment of Histone-Fold Protein Nf-y Distinguishing It from Sp1 and Sp3
- GAGA Factor Maintains Nucleosome-Free Regions and Has a Role in RNA Polymerase II Recruitment to Promoters
- Neurospora Importin α Is Required for Normal Heterochromatic Formation and DNA Methylation
- Ccr4-Not Regulates RNA Polymerase I Transcription and Couples Nutrient Signaling to the Control of Ribosomal RNA Biogenesis
- Phenotype Specific Analyses Reveal Distinct Regulatory Mechanism for Chronically Activated p53
- A Systems-Level Interrogation Identifies Regulators of Blood Cell Number and Survival
- Morphological Mutations: Lessons from the Cockscomb
- Genetic Interaction Mapping Reveals a Role for the SWI/SNF Nucleosome Remodeler in Spliceosome Activation in Fission Yeast
- The Role of China in the Global Spread of the Current Cholera Pandemic
- The Nuclear Receptor DAF-12 Regulates Nutrient Metabolism and Reproductive Growth in Nematodes
- A Zinc Finger Motif-Containing Protein Is Essential for Chloroplast RNA Editing
- Resistance to Gray Leaf Spot of Maize: Genetic Architecture and Mechanisms Elucidated through Nested Association Mapping and Near-Isogenic Line Analysis
- Small Regulatory RNA-Induced Growth Rate Heterogeneity of
- Mitochondrial Dysfunction Reveals the Role of mRNA Poly(A) Tail Regulation in Oculopharyngeal Muscular Dystrophy Pathogenesis
- Complex Genomic Rearrangements at the Locus Include Triplication and Quadruplication
- Male-Biased Aganglionic Megacolon in the TashT Mouse Line Due to Perturbation of Silencer Elements in a Large Gene Desert of Chromosome 10
- Sex Ratio Meiotic Drive as a Plausible Evolutionary Mechanism for Hybrid Male Sterility
- Tertiary siRNAs Mediate Paramutation in .
- RECG Maintains Plastid and Mitochondrial Genome Stability by Suppressing Extensive Recombination between Short Dispersed Repeats
- Escape from X Inactivation Varies in Mouse Tissues
- Opposite Phenotypes of Muscle Strength and Locomotor Function in Mouse Models of Partial Trisomy and Monosomy 21 for the Proximal Region
- Glycosyl Phosphatidylinositol Anchor Biosynthesis Is Essential for Maintaining Epithelial Integrity during Embryogenesis
- Hyperdiverse Gene Cluster in Snail Host Conveys Resistance to Human Schistosome Parasites
- The Class Homeodomain Factors and Cooperate in . Embryonic Progenitor Cells to Regulate Robust Development
- Recombination between Homologous Chromosomes Induced by Unrepaired UV-Generated DNA Damage Requires Mus81p and Is Suppressed by Mms2p
- Synergistic Interactions between Orthologues of Genes Spanned by Human CNVs Support Multiple-Hit Models of Autism
- Gene Networks Underlying Convergent and Pleiotropic Phenotypes in a Large and Systematically-Phenotyped Cohort with Heterogeneous Developmental Disorders
- The ATM Signaling Cascade Promotes Recombination-Dependent Pachytene Arrest in Mouse Spermatocytes
- Combinatorial Control of Light Induced Chromatin Remodeling and Gene Activation in
- Linking Aβ42-Induced Hyperexcitability to Neurodegeneration, Learning and Motor Deficits, and a Shorter Lifespan in an Alzheimer’s Model
- The Complex Contributions of Genetics and Nutrition to Immunity in
- NatB Domain-Containing CRA-1 Antagonizes Hydrolase ACER-1 Linking Acetyl-CoA Metabolism to the Initiation of Recombination during . Meiosis
- Transcriptomic Profiling of Reveals Reprogramming of the Crp Regulon by Temperature and Uncovers Crp as a Master Regulator of Small RNAs
- Osteopetrorickets due to Snx10 Deficiency in Mice Results from Both Failed Osteoclast Activity and Loss of Gastric Acid-Dependent Calcium Absorption
- A Genomic Portrait of Haplotype Diversity and Signatures of Selection in Indigenous Southern African Populations
- Sequence Features and Transcriptional Stalling within Centromere DNA Promote Establishment of CENP-A Chromatin
- Inhibits Neuromuscular Junction Growth by Downregulating the BMP Receptor Thickveins
- Replicative DNA Polymerase δ but Not ε Proofreads Errors in and in
- Unsaturation of Very-Long-Chain Ceramides Protects Plant from Hypoxia-Induced Damages by Modulating Ethylene Signaling in
- The Small Protein MntS and Exporter MntP Optimize the Intracellular Concentration of Manganese
- A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension
- Pervasive Variation of Transcription Factor Orthologs Contributes to Regulatory Network Evolution
- Network Analyses Reveal Novel Aspects of ALS Pathogenesis
- A Role for the Budding Yeast Separase, Esp1, in Ty1 Element Retrotransposition
- Nab3 Facilitates the Function of the TRAMP Complex in RNA Processing via Recruitment of Rrp6 Independent of Nrd1
- A RecA Protein Surface Required for Activation of DNA Polymerase V
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Clonality and Evolutionary History of Rhabdomyosarcoma
- Morphological Mutations: Lessons from the Cockscomb
- Maternal Filaggrin Mutations Increase the Risk of Atopic Dermatitis in Children: An Effect Independent of Mutation Inheritance
- Transcriptomic Profiling of Reveals Reprogramming of the Crp Regulon by Temperature and Uncovers Crp as a Master Regulator of Small RNAs
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy