Integrating transcriptomic network reconstruction and eQTL analyses reveals mechanistic connections between genomic architecture and Brassica rapa development
Autoři:
Robert L. Baker aff001; Wen Fung Leong aff002; Marcus T. Brock aff003; Matthew J. Rubin aff003; R. J. Cody Markelz aff004; Stephen Welch aff002; Julin N. Maloof aff004; Cynthia Weinig aff003
Působiště autorů:
Department of Biology, Miami University, Oxford, Ohio, United States of America
aff001; Department of Agronomy, Kansas State University, Manhattan, Kansas, United States of America
aff002; Department of Botany, University of Wyoming, Laramie, Wyoming, United States of America
aff003; Department of Plant Biology, University of California Davis, Davis, California, United States of America
aff004
Vyšlo v časopise:
Integrating transcriptomic network reconstruction and eQTL analyses reveals mechanistic connections between genomic architecture and Brassica rapa development. PLoS Genet 15(9): e1008367. doi:10.1371/journal.pgen.1008367
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1008367
Souhrn
Plant developmental dynamics can be heritable, genetically correlated with fitness and yield, and undergo selection. Therefore, characterizing the mechanistic connections between the genetic architecture governing plant development and the resulting ontogenetic dynamics of plants in field settings is critically important for agricultural production and evolutionary ecology. We use hierarchical Bayesian Function-Valued Trait (FVT) models to estimate Brassica rapa growth curves throughout ontogeny, across two treatments, and in two growing seasons. We find that the shape of growth curves is relatively plastic across environments compared to final height, which is comparatively robust. There are trade-offs between growth rate and duration, indicating that selection for maximum yields at early harvest dates may come at the expense of late harvest yields and vice versa. We generate eigengene modules and determine which are co-expressed with FVT traits using a Weighted Gene Co-expression Analysis. Independently, we seed a Mutual Rank co-expression network model with FVT traits to identify specific genes and gene networks related to FVT. GO-analyses of eigengene modules indicate roles for actin/cytoskeletal genes, herbivore resistance/wounding responses, and cell division, while MR networks demonstrate a close association between metabolic regulation and plant growth. We determine that combining FVT Quantitative Trait Loci (QTL) and MR genes/WGCNA eigengene expression profiles better characterizes phenotypic variation than any single data type (i.e. QTL, gene, or eigengene alone). Our network analysis allows us to employ a targeted eQTL analysis, which we use to identify regulatory hotspots for FVT. We examine cis vs. trans eQTL that mechanistically link FVT QTL with structural trait variation. Colocalization of FVT, gene, and eigengene eQTL provide strong evidence for candidate genes influencing plant height. The study is the first to explore eQTL for FVT, and specifically do so in agroecologically relevant field settings.
Klíčová slova:
Biology and life sciences – Genetics – Gene expression – Plant genetics – Plant science – Research and analysis methods – Molecular biology – Genetic loci – Quantitative trait loci – Gene regulation – Gene identification and analysis – Genetic networks – Phenotypes – Molecular biology techniques – Gene mapping – Computer and information sciences – Network analysis
Zdroje
1. Baker RL, Leong WF, Brock MT, Markelz RJC, Covington MF, Devisetty UK, et al. Modeling development and quantitative trait mapping reveal independent genetic modules for leaf size and shape. New Phytol. 2015;208: 257–268. doi: 10.1111/nph.13509 26083847
2. Kulbaba MW, Clocher IC, Harder LD. Inflorescence characteristics as function-valued traits: Analysis of heritability and selection on architectural effects. J Syst Evol. 2017;55: 559–565. doi: 10.1111/jse.12252
3. Prioul J-L, Quarrie S, Causse M, de Vienne D. Dissecting complex physiological functions through the use of molecular quantitative genetics. J Exp Bot. 1997;48: 1151–1163. Available: http://dx.doi.org/10.1093/jxb/48.6.1151
4. Mackay TFC. Epistasis and quantitative traits: using model organisms to study gene–gene interactions. Nat Rev Genet. 2013;15: 22. Available: doi: 10.1038/nrg3627 24296533
5. Csilléry K, Rodríguez-Verdugo A, Rellstab C, Guillaume F. Detecting the genomic signal of polygenic adaptation and the role of epistasis in evolution. Mol Ecol. 2018;27: 606–612. doi: 10.1111/mec.14499 29385652
6. Nozue K, Devisetty UK, Lekkala S, Mueller-Moule P, Bak A, Casteel CL, et al. Network analysis reveals a role for salicylic acid pathway components in shade avoidance. Plant Physiol. 2018; Available: http://www.plantphysiol.org/content/early/2018/10/22/pp.18.00920.abstract
7. Schaefer R, Michno J-M, Jeffers J, Hoekenga OA, Dilkes BP, Baxter IR, et al. Integrating co-expression networks with GWAS to prioritize causal genes in maize. Plant Cell. 2018; Available: http://www.plantcell.org/content/early/2018/11/09/tpc.18.00299.abstract
8. Luo J, Xu P, Cao P, Wan H, Lv X, Xu S, et al. Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses [Internet]. Frontiers in Molecular Neuroscience. 2018. p. 102. Available: doi: 10.3389/fnmol.2018.00102 29674951
9. Hitzemann R, Malmanger B, Reed C, Lawler M, Hitzemann B, Coulombe S, et al. A strategy for the integration of QTL, gene expression, and sequence analyses. Mamm Genome. 2003;14: 733–747. doi: 10.1007/s00335-003-2277-9 14722723
10. Li R, Jeong K, Davis JT, Kim S, Lee S, Michelmore RW, et al. Integrated QTL and eQTL Mapping Provides Insights and Candidate Genes for Fatty Acid Composition, Flowering Time, and Growth Traits in a F2 Population of a Novel Synthetic Allopolyploid Brassica napus. Front Plant Sci. 2018;9: 1632. doi: 10.3389/fpls.2018.01632 30483289
11. Wu WR, Li WM, Tang DZ, Lu HR, Worland AJ. Time-related mapping of quantitative trait loci underlying tiller number in rice. Genetics. 1999;151: 297–303. Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1460454/ 9872968
12. Griswold CK, Gomulkiewicz R, Heckman N. Hypothesis testing in comparative and experimental studies of Function-Valued Traits. Evolution (N Y). 2008;62: 1229–1242. doi: 10.1111/j.1558-5646.2008.00340.x 18266991
13. Kingsolver JG, Gomulkiewicz R, Carter PA. Variation, selection and evolution of function-valued traits. Genetica. 2001;112: 87–104. doi: 10.1023/A:1013323318612 11838789
14. Wu R, Lin M. Functional mapping—how to map and study the genetic architecture of dynamic complex traits. Nat Rev Genet. 2006;7: 229. Available: doi: 10.1038/nrg1804 16485021
15. Stinchcombe JR, Kirkpatrick M. Genetics and evolution of function-valued traits: understanding environmentally responsive phenotypes. Trends Ecol Evol. 2012;27: 637–647. doi: 10.1016/j.tree.2012.07.002 22898151
16. Hernandez KM. Understanding the genetic architecture of complex traits using the function-valued approach. New Phytol. 2015;208: 1–3. doi: 10.1111/nph.13607 26311281
17. Raines CA, Paul MJ. Products of leaf primary carbon metabolism modulate the developmental programme determining plant morphology. J Exp Bot. 2006;57: 1857–1862. Available: doi: 10.1093/jxb/erl011 16714302
18. Schneidereit J, Häusler RE, Fiene G, Kaiser WM, Weber APM. Antisense repression reveals a crucial role of the plastidic 2-oxoglutarate/malate translocator DiT1 at the interface between carbon and nitrogen metabolism. Plant J. 2005;45: 206–224. doi: 10.1111/j.1365-313X.2005.02594.x 16367965
19. Carvalho SMP, Heuvelink E. Effect of assimilate availability on flower characteristics and plant height of cut chrysanthemum: an integrated study. J Hortic Sci Biotechnol. 2003;78: 711–720. doi: 10.1080/14620316.2003.11511688
20. Hammer GL, Chapman S, van Oosterom E, Podlich DW. Trait physiology and crop modelling as a framework to link phenotypic complexity to underlying genetic systems. Aust J Agric Res. 2005;56: 947–960. Available: https://doi.org/10.1071/AR05157
21. Baker RL, Leong WF, An N, Brock MT, Rubin MJ, Welch S, et al. Bayesian estimation and use of high-throughput remote sensing indices for quantitative genetic analyses of leaf growth. Theor Appl Genet. 2018;131: 283–298. doi: 10.1007/s00122-017-3001-6 29058049
22. Baker RL, Leong WF, Welch S, Weinig C. Mapping and Predicting Non-linear Brassica rapa Growth Phenotypes Based on Bayesian and Frequentist Complex Trait Estimation. G3 Genes|Genomes|Genetics. 2018;8: 1247–1258. doi: 10.1534/g3.117.300350 29467188
23. Li P, Ponnala L, Gandotra N, Wang L, Si Y, Tausta SL, et al. The developmental dynamics of the maize leaf transcriptome. Nat Genet. 2010;42: 1060. Available: doi: 10.1038/ng.703 21037569
24. Schmid M, Davison TS, Henz SR, Pape UJ, Demar M, Vingron M, et al. A gene expression map of Arabidopsis thaliana development. Nat Genet. 2005;37: 501. Available: doi: 10.1038/ng1543 15806101
25. Jiang L, Clavijo JA, Sun L, Zhu X, Bhakta MS, Gezan SA, et al. Plastic expression of heterochrony quantitative trait loci (hQTLs) for leaf growth in the common bean (Phaseolus vulgaris). New Phytol. 2015;207: 872–882. doi: 10.1111/nph.13386 25816915
26. Zhu Z, Zhang F, Hu H, Bakshi A, Robinson MR, Powell JE, et al. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat Genet. 2016;48: 481. Available: doi: 10.1038/ng.3538 27019110
27. Munkvold JD, Laudencia-Chingcuanco D, Sorrells ME. Systems Genetics of Environmental Response in the Mature Wheat Embryo. Genetics. 2013;194: 265–277. doi: 10.1534/genetics.113.150052 23475987
28. Ponsuksili S, Siengdee P, Du Y, Trakooljul N, Murani E, Schwerin M, et al. Identification of Common Regulators of Genes in Co-Expression Networks Affecting Muscle and Meat Properties. PLoS One. 2015;10: e0123678. Available: doi: 10.1371/journal.pone.0123678 25875247
29. Gibson G, Weir B. The quantitative genetics of transcription. Trends Genet. 2005;21: 616–623. doi: 10.1016/j.tig.2005.08.010 16154229
30. Hammond JP, Mayes S, Bowen HC, Graham NS, Hayden RM, Love CG, et al. Regulatory Hotspots Are Associated with Plant Gene Expression under Varying Soil Phosphorus Supply in <em>Brassica rapa</em> Plant Physiol. 2011;156: 1230 LP–1241. Available: http://www.plantphysiol.org/content/156/3/1230.abstract
31. Schadt EE, Monks SA, Drake TA, Lusis AJ, Che N, Colinayo V, et al. Genetics of gene expression surveyed in maize, mouse and man. Nature. 2003;422: 297. Available: doi: 10.1038/nature01434 12646919
32. West MAL, Kim K, Kliebenstein DJ, van Leeuwen H, Michelmore RW, Doerge RW, et al. Global eQTL Mapping Reveals the Complex Genetic Architecture of Transcript-Level Variation in Arabidopsis. Genetics. 2007;175: 1441–1450. doi: 10.1534/genetics.106.064972 17179097
33. Tian J, Keller MP, Broman AT, Kendziorski C, Yandell BS, Attie AD, et al. The Dissection of Expression Quantitative Trait Locus Hotspots. Genetics. 2016;202: 1563 LP–1574. doi: 10.1534/genetics.115.183624 26837753
34. Law CN, Snape JW, Worland AJ. The genetical relationship between height and yield in wheat. Heredity (Edinb). 1978;40: 133. Available: http://dx.doi.org/10.1038/hdy.1978.13
35. Bowman JL, Smyth DR, Meyerowitz EM. The ABC model of flower development: then and now. Development. 2012;139: 4095 LP–4098. Available: http://dev.biologists.org/content/139/22/4095.abstract
36. Schmitt J, Stinchcombe JR, Heschel MS, Huber H. The Adaptive Evolution of Plasticity: Phytochrome-Mediated Shade Avoidance Responses1. Integr Comp Biol. 2003;43: 459–469. Available: doi: 10.1093/icb/43.3.459 21680454
37. Klingenberg CP. Studying morphological integration and modularity at multiple levels: concepts and analysis. Philos Trans R Soc B Biol Sci. 2014;369: 20130249. doi: 10.1098/rstb.2013.0249 25002695
38. Yin X, McClure MA, Jaja N, Tyler DD, Hayes RM. In-Season Prediction of Corn Yield Using Plant Height under Major Production Systems. Agron J. 2011;103: 923–929. doi: 10.2134/agronj2010.0450
39. Tanger P, Klassen S, Mojica JP, Lovell JT, Moyers BT, Baraoidan M, et al. Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice. Sci Rep. 2017;7: 42839. Available: doi: 10.1038/srep42839 28220807
40. Reiser L, Modrusan Z, Margossian L, Samach A, Ohad N, Haughn GW, et al. The BELL1 gene encodes a homeodomain protein involved in pattern formation in the Arabidopsis ovule primordium. Cell. 1995;83: 735–742. doi: 10.1016/0092-8674(95)90186-8 8521490
41. Rutjens B, Bao D, Van Eck-Stouten E, Brand M, Smeekens S, Proveniers M. Shoot apical meristem function in Arabidopsis requires the combined activities of three BEL1-like homeodomain proteins. Plant J. 2009;58: 641–654. doi: 10.1111/j.1365-313X.2009.03809.x 19175771
42. Nakamura Y, Tsuchiya M, Ohta H. Plastidic Phosphatidic Acid Phosphatases Identified in a Distinct Subfamily of Lipid Phosphate Phosphatases with Prokaryotic Origin. J Biol Chem. 2007;282: 29013–29021. doi: 10.1074/jbc.M704385200 17652095
43. Zhu J, Fu X, Koo YD, Zhu J-K, Jenney FE, Adams MWW, et al. An Enhancer Mutant of Arabidopsis salt overly sensitive 3 Mediates both Ion Homeostasis and the Oxidative Stress Response. Mol Cell Biol. 2007;27: 5214–5224. doi: 10.1128/MCB.01989-06 17485445
44. Rubin G, Tohge T, Matsuda F, Saito K, Scheible W-R. Members of the LBD Family of Transcription Factors Repress Anthocyanin Synthesis and Affect Additional Nitrogen Responses in Arabidopsis. Plant Cell. 2009;21: 3567–3584. doi: 10.1105/tpc.109.067041 19933203
45. Albinsky D, Kusano M, Higuchi M, Hayashi N, Kobayashi M, Fukushima A, et al. Metabolomic Screening Applied to Rice FOX Arabidopsis Lines Leads to the Identification of a Gene-Changing Nitrogen Metabolism. Mol Plant. 2010;3: 125–142. doi: 10.1093/mp/ssp069 20085895
46. Clark TJ, Lu Y. Analysis of Loss-of-Function Mutants in Aspartate Kinase and Homoserine Dehydrogenase Genes Points to Complexity in the Regulation of Aspartate-Derived Amino Acid Contents. Plant Physiol. 2015;168: 1512–1526. doi: 10.1104/pp.15.00364 26063505
47. Gutensohn M, Klempien A, Kaminaga Y, Nagegowda DA, Negre‐Zakharov F, Huh J-H, et al. Role of aromatic aldehyde synthase in wounding/herbivory response and flower scent production in different Arabidopsis ecotypes. Plant J. 2011;66: 591–602. doi: 10.1111/j.1365-313X.2011.04515.x 21284755
48. Schadt EE, Molony C, Chudin E, Hao K, Yang X, Lum PY, et al. Mapping the Genetic Architecture of Gene Expression in Human Liver. Abecassis G, editor. PLoS Biol. 2008;6: e107. doi: 10.1371/journal.pbio.0060107 18462017
49. Brown CD, Mangravite LM, Engelhardt BE. Integrative Modeling of eQTLs and Cis-Regulatory Elements Suggests Mechanisms Underlying Cell Type Specificity of eQTLs. Gibson G, editor. PLoS Genet. 2013;9: e1003649. doi: 10.1371/journal.pgen.1003649 23935528
50. Lovell JT, Jenkins J, Lowry DB, Mamidi S, Sreedasyam A, Weng X, et al. The genomic landscape of molecular responses to natural drought stress in Panicum hallii. Nat Commun. 2018;9: 5213. doi: 10.1038/s41467-018-07669-x 30523281
51. Doss S, Schadt EE, Drake TA, Lusis AJ. Cis-acting expression quantitative trait loci in mice. Genome Res. 2005;15: 681–691. doi: 10.1101/gr.3216905 15837804
52. Hansen BG, Halkier BA, Kliebenstein DJ. Identifying the molecular basis of QTLs: eQTLs add a new dimension. Trends Plant Sci. 2008;13: 72–77. doi: 10.1016/j.tplants.2007.11.008 18262820
53. Swanson-Wagner RA, DeCook R, Jia Y, Bancroft T, Ji T, Zhao X, et al. Paternal Dominance of Trans-eQTL Influences Gene Expression Patterns in Maize Hybrids. Science (80-). 2009;326: 1118 LP–1120. Available: http://science.sciencemag.org/content/326/5956/1118.abstract
54. Wittkopp PJ, Haerum BK, Clark AG. Regulatory changes underlying expression differences within and between Drosophila species. Nat Genet. 2008;40: 346. Available: doi: 10.1038/ng.77 18278046
55. Goncalves A, Leigh-Brown S, Thybert D, Stefflova K, Turro E, Flicek P, et al. Extensive compensatory cis-trans regulation in the evolution of mouse gene expression. Genome Res. 2012;22: 2376–2384. doi: 10.1101/gr.142281.112 22919075
56. O’Quin KE, Schulte JE, Patel Z, Kahn N, Naseer Z, Wang H, et al. Evolution of cichlid vision via trans-regulatory divergence. BMC Evol Biol. 2012;12: 251. doi: 10.1186/1471-2148-12-251 23267665
57. Kokichi H, Shyam P. Ethnobotany and Evolutionary Origin of Indian Oleiferous Brassicae. Indian J Genet Plant Breed. 1984;44: 102–112.
58. Markelz RJC, Covington MF, Brock MT, Devisetty UK, Kliebenstein DJ, Weinig C, et al. Using RNA-seq for Genomic Scaffold Placement, Correcting Assemblies, and Genetic Map Creation in a Common <em>Brassica rapa</em> Mapping Population. G3 Genes|Genomes|Genetics. 2017; Available: http://www.g3journal.org/content/early/2017/05/24/g3.117.043000.abstract
59. Brock MT, Weinig C. Plasticity and Environment-Specific Covariances: An investigation of floral-vegetative and within flower correlations. Evolution (N Y). 2007;61: 2913–2924. doi: 10.1111/j.1558-5646.2007.00240.x 17941839
60. Iniguez-Luy FL, Lukens L, Farnham MW, Amasino RM, Osborn TC. Development of public immortal mapping populations, molecular markers and linkage maps for rapid cycling Brassica rapa and B. oleracea. Theor Appl Genet. 2009;120: 31–43. doi: 10.1007/s00122-009-1157-4 19784615
61. Vigil MF, Anderson RL, Beard WE. Base Temperature and Growing-Degree-Hour Requirements for the Emergence of Canola. Crop Sci. 1997;37: 844–849.
62. Jaffrézic F, Pletcher SD. Statistical models for estimating the genetic basis of repeated measures and other function-valued traits. Genetics. 2000;156: 913–922. Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1461268/ 11014836
63. Stinchcombe JR, Izem R, Shane HM, McGoey B V., Schmitt J. Across-Environment genetic correlations and the frequency of selective environments shape the evolutionary dynamics of growth rate in Impatiens capensis. Evolution (N Y). 2010;64: 2887–2903. doi: 10.1111/j.1558-5646.2010.01060.x 20662920
64. Chib S, Greenberg E. Understanding the Metropolis-Hastings Algorithm. Am Stat. 1995;49: 327–335. doi: 10.1080/00031305.1995.10476177
65. Patil A, Huard D, Fonnesbeck C. PyMC: Bayesian Stochastic Modelling in Python. J Stat Software, Artic. 2010;35: 1–81. doi: 10.18637/jss.v035.i04
66. Kruschke JK. Doing Bayesian Data Analysis: A tutorial with R, BUGS, and Stan. 3rd ed. Academic Press; 2014.
67. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria; 2016.
68. Halekoh U, Højsgaard S. A Kenward-Roger Approximation and Parametric Bootsrap Methods for Tests in Linear Mixed Models—The R Package pbkrtest. J Stat Software2. 2014;59: 1–30.
69. Bates D, Maechler M, Bolker B, Walker S, Christensen RHBC, Singmann H, et al. lme4: Linear Mixed-Effects Models using “Eigen” and S4 [Internet]. 2018. Available: https://cran.r-project.org/web/packages/lme4/index.html
70. Kuznetsova A, Brockhoof PB, Christensen RHBC. lmerTest: Tests in Linear Mixed Effects Models. 2018.
71. Broman KW, Wu H, Sen S, Churchill GA. R/qtl: QTL mapping in experimental crosses. Bioinformatics. 2003;19: 899–890. doi: 10.1093/bioinformatics/btg110
72. Broman KW, Sen S. A guide to QTL Mapping with R/qtl. New York: Springer; 2009. doi: 10.1007/978-0-387-92125-9
73. Voorrips RE. MapChart: Software for the Graphical Presentation of Linkage Maps and QTLs. J Hered. 2002;93: 77–78. Available: doi: 10.1093/jhered/93.1.77 12011185
74. Cheng F, Liu S, Wu J, Fang L, Sun S, Liu B, et al. BRAD, the genetics and genomics database for Brassica plants. BMC Plant Biol. 2011;11: 136. doi: 10.1186/1471-2229-11-136 21995777
75. Kumar R, Ichihashi Y, Kimura S, Chitwood DH, Headland LR, Peng J, et al. A High-Throughput Method for Illumina RNA-Seq Library Preparation. Front Plant Sci. 2012;3: 202. doi: 10.3389/fpls.2012.00202 22973283
76. Devisetty UK, Covington MF, Tat A V, Lekkala S, Maloof JN. Polymorphism Identification and Improved Genome Annotation of Brassica rapa Through Deep RNA Sequencing. G3 Genes|Genomes|Genetics. 2014;4: 2065–2078. doi: 10.1534/g3.114.012526 25122667
77. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25: 1754–1760. doi: 10.1093/bioinformatics/btp324 19451168
78. Robinson MD, Oshlack A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 2010;11: R25. doi: 10.1186/gb-2010-11-3-r25 20196867
79. Law CW, Chen Y, Shi W, Smyth GK. voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 2014;15: R29. doi: 10.1186/gb-2014-15-2-r29 24485249
80. Obayashi T, Kinoshita K. Rank of Correlation Coefficient as a Comparable Measure for Biological Significance of Gene Coexpression. DNA Res. 2009;16: 249–260. doi: 10.1093/dnares/dsp016 19767600
81. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990;215: 403–410. doi: 10.1016/S0022-2836(05)80360-2 2231712
82. Zhang B, Horvath S. A General Framework for Weighted Gene Co-Expression Network Analysis. Stat Appl Genet Mol Biol. 2005;4.
83. 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
84. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25: 2078–2079. doi: 10.1093/bioinformatics/btp352 19505943
85. Tange O. GNU Parallel—The Command-Line Power Tool.; login USENIX Mag. 2011;36: 42–47. http://dx.doi.org/10.5281/zenodo.16303
86. Garrison E, Marth G. Haplotype-based variant detection from short-read sequencing. arXiv:12073907 [q-bio]. 2012;
87. Cingolani P, Platts A, Wang LL, Coon M, Nguyen T, Wang L, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin). 2012;6: 80–92. doi: 10.4161/fly.19695 22728672
88. R Core Team. R: A language and environment for statistical computing [Internet]. Vienna, Australia; 2017. Available: https://www.r-project.org/
89. Thorvaldsdóttir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2013;14: 178–192. doi: 10.1093/bib/bbs017 22517427
90. Zeng ZB. Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci. Proc Natl Acad Sci U S A. 1993;90: 10972–10976. Available: doi: 10.1073/pnas.90.23.10972 8248199
91. Doerge RW, Churchill GA. Permutation Tests for Multiple Loci Affecting a Quantitative Character. Genetics. 1996;142: 285 LP–294. Available: http://www.genetics.org/content/142/1/285.abstract
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2019 Číslo 9
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Origins of DNA replication
- Environmental and epigenetic regulation of Rider retrotransposons in tomato
- Integrating transcriptomic network reconstruction and eQTL analyses reveals mechanistic connections between genomic architecture and Brassica rapa development
- Temperature preference can bias parental genome retention during hybrid evolution