add to intro

DESCRIPTION

@@ -1,6 +1,6 @@
 Package: rnaseqDTU
 Title: RNA-seq workflow for differential transcript usage following Salmon quantification
-Version: 0.99.15
+Version: 0.99.16
 Date: 2018-06-27
 Authors@R: c(person(role=c("aut", "cre"), "Michael", "Love", email = "[email protected]"),
              person(role=c("aut"), "Charlotte", "Soneson"),

vignettes/bibliography.bib

@@ -1,3 +1,45 @@
+@article{Reyes2018,
+ author = {Reyes, Alejandro and Huber, Wolfgang},
+ title = {Alternative start and termination sites of transcription drive most transcript isoform differences across human tissues},
+ journal = {Nucleic Acids Research},
+ volume = 46,
+ number = 2,
+ pages = {582–-592},
+ year = 2018
+}
+
+@article{Scotti2018,
+  author = {Scotti, Marina M. and Swanson, Maurice S.},
+  title = {{RNA mis-splicing in disease}},
+  journal = {Nature Reviews Genetics},
+  volume = 17,
+  number = 1,
+  pages = {19--32},
+  year = 2018
+}
+
+@Article{Climente2017,
+author={Climente-Gonz{\'a}lez, H{\'e}ctor
+and Porta-Pardo, Eduard
+and Godzik, Adam
+and Eyras, Eduardo},
+title={The Functional Impact of Alternative Splicing in Cancer},
+journal={Cell Reports},
+year={2017},
+volume={20},
+number={9},
+pages={2215-2226}
+}
+
+@article{GTEx,
+author={GTEx Consortium, and Aguet, Fran{\c{c}}ois and Brown, Andrew A. and Castel, Stephane E. and Davis, Joe R. and He, Yuan and Jo, Brian and Mohammadi, Pejman and Park, YoSon and Parsana, Princy and Segr{\`e}, Ayellet V. and Strober, Benjamin J. and Zappala, Zachary and Cummings, Beryl B. and Gelfand, Ellen T. and Hadley, Kane and Huang, Katherine H. and Lek, Monkol and Li, Xiao and Nedzel, Jared L. and Nguyen, Duyen Y. and Noble, Michael S. and Sullivan, Timothy J. and Tukiainen, Taru and MacArthur, Daniel G. and Getz, Gad and Addington, Anjene and Guan, Ping and Koester, Susan and Little, A. Roger and Lockhart, Nicole C. and Moore, Helen M. and Rao, Abhi and Struewing, Jeffery P. and Volpi, Simona and Brigham, Lori E. and Hasz, Richard and Hunter, Marcus and Johns, Christopher and Johnson, Mark and Kopen, Gene and Leinweber, William F. and Lonsdale, John T. and McDonald, Alisa and Mestichelli, Bernadette and Myer, Kevin and Roe, Bryan and Salvatore, Michael and Shad, Saboor and Thomas, Jeffrey A. and Walters, Gary and Washington, Michael and Wheeler, Joseph and Bridge, Jason and Foster, Barbara A. and Gillard, Bryan M. and Karasik, Ellen and Kumar, Rachna and Miklos, Mark and Moser, Michael T. and Jewell, Scott D. and Montroy, Robert G. and Rohrer, Daniel C. and Valley, Dana and Mash, Deborah C. and Davis, David A. and Sobin, Leslie and Barcus, Mary E. and Branton, Philip A. and Abell, Nathan S. and Balliu, Brunilda and Delaneau, Olivier and Fr{\'e}sard, Laure and Gamazon, Eric R. and Garrido-Mart{\'i}n, Diego and Gewirtz, Ariel D. H. and Gliner, Genna and Gloudemans, Michael J. and Han, Buhm and He, Amy Z. and Hormozdiari, Farhad and Li, Xin and Liu, Boxiang and Kang, Eun Yong and McDowell, Ian C. and Ongen, Halit and Palowitch, John J. and Peterson, Christine B. and Quon, Gerald and Ripke, Stephan and Saha, Ashis and Shabalin, Andrey A. and Shimko, Tyler C. and Sul, Jae Hoon and Teran, Nicole A. and Tsang, Emily K. and Zhang, Hailei and Zhou, Yi-Hui and Bustamante, Carlos D. and Cox, Nancy J. and Guig{\'o}, Roderic and Kellis, Manolis and McCarthy, Mark I. and Conrad, Donald F. and Eskin, Eleazar and Li, Gen and Nobel, Andrew B. and Sabatti, Chiara and Stranger, Barbara E. and Wen, Xiaoquan and Wright, Fred A. and Ardlie, Kristin G. and Dermitzakis, Emmanouil T. and Lappalainen, Tuuli and Handsaker, Robert E. and Kashin, Seva and Karczewski, Konrad J. and Nguyen, Duyen T. and Trowbridge, Casandra A. and Barshir, Ruth and Basha, Omer and Battle, Alexis and Bogu, Gireesh K. and Brown, Andrew and Brown, Christopher D. and Chen, Lin S. and Chiang, Colby and Damani, Farhan N. and Engelhardt, Barbara E. and Ferreira, Pedro G. and Guigo, Roderic and Hall, Ira M. and Howald, Cedric and Kyung Im, Hae and Yong Kang, Eun and Kim, Yungil and Kim-Hellmuth, Sarah and Mangul, Serghei and Monlong, Jean and Montgomery, Stephen B. and Mu{\~n}oz-Aguirre, Manuel and Ndungu, Anne W. and Nicolae, Dan L. and Oliva, Meritxell and Panousis, Nikolaos and Papasaikas, Panagiotis and Payne, Anthony J. and Quan, Jie and Reverter, Ferran and Sammeth, Michael and Scott, Alexandra J. and Sodaei, Reza and Stephens, Matthew and Urbut, Sarah and van de Bunt, Martijn and Wang, Gao and Xi, Hualin S. and Yeger-Lotem, Esti and Zaugg, Judith B. and Akey, Joshua M. and Bates, Daniel and Chan, Joanne and Claussnitzer, Melina and Demanelis, Kathryn and Diegel, Morgan and Doherty, Jennifer A. and Feinberg, Andrew P. and Fernando, Marian S. and Halow, Jessica and Hansen, Kasper D. and Haugen, Eric and Hickey, Peter F. and Hou, Lei and Jasmine, Farzana and Jian, Ruiqi and Jiang, Lihua and Johnson, Audra and Kaul, Rajinder and Kibriya, Muhammad G. and Lee, Kristen and Billy Li, Jin and Li, Qin and Lin, Jessica and Lin, Shin and Linder, Sandra and Linke, Caroline and Liu, Yaping and Maurano, Matthew T. and Molinie, Benoit and Nelson, Jemma and Neri, Fidencio J. and Park, Yongjin and Pierce, Brandon L. and Rinaldi, Nicola J. and Rizzardi, Lindsay F. and Sandstrom, Richard and Skol, Andrew and Smith, Kevin S. and Snyder, Michael P. and Stamatoyannopoulos, John and Tang, Hua and Wang, Li and Wang, Meng and Van Wittenberghe, Nicholas and Wu, Fan and Zhang, Rui and Nierras, Concepcion R. and Carithers, Latarsha J. and Vaught, Jimmie B. and Gould, Sarah E. and Lockart, Nicole C. and Martin, Casey and Addington, Anjene M. and Koester, Susan E. and Roe, Brian and Valley, Dana R. and Undale, Anita H. and Smith, Anna M. and Tabor, David E. and Roche, Nancy V. and McLean, Jeffrey A. and Vatanian, Negin and Robinson, Karna L. and Valentino, Kimberly M. and Qi, Liqun and Hunter, Steven and Hariharan, Pushpa and Singh, Shilpi and Um, Ki Sung and Matose, Takunda and Tomaszewski, Maria M. and Barker, Laura K. and Mosavel, Maghboeba and Siminoff, Laura A. and Traino, Heather M. and Flicek, Paul and Juettemann, Thomas and Ruffier, Magali and Sheppard, Dan and Taylor, Kieron and Trevanion, Stephen J. and Zerbino, Daniel R. and Craft, Brian and Goldman, Mary and Haeussler, Maximilian and Kent, W. James and Lee, Christopher M. and Paten, Benedict and Rosenbloom, Kate R. and Vivian, John and Zhu, Jingchun},
+title={Genetic effects on gene expression across human tissues},
+journal={Nature},
+year={2017},
+volume={550},
+pages={204 EP  -},
+}
+
 @article{Patro2017Salmon,
   author = {Patro, Rob and Duggal, Geet and Love, Michael I. and Irizarry, Rafael A. and Kingsford, Carl},
   journal = {Nature Methods},

vignettes/rnaseqDTU.Rmd

@@ -68,6 +68,25 @@ transcript usage within a gene. If the amount of expression
 switches among two or more isoforms of a gene, then the total gene
 expression may not change by a detectable amount, but 
 the differential transcript usage (DTU) is nevertheless biologically relevant.
+DTU is common when comparing expression across cell types: recent
+analysis of the Genotype-Tissue Expression Project (GTEx) [@GTEx]
+dataset demonstrated that half of all expressed genes contained
+tissue-specific isoforms [@Reyes2018]. DTU may produce functionally
+different gene products through alternative splicing and changes to
+the coding sequence of the transcript, and DTU may result in
+transcripts with different untranslated regions on the 5' or 3' end of
+the transcript, which may affect recognition sites of RNA binding
+proteins.  [@Reyes2018] found that the later case, alternative usage
+of transcription start and termination sites, was a more common event
+than alternative splicing when examining DTU events across tissues in
+GTEx.  Specific patterns of DTU have been identified in a number of
+diseases, including cancer, retinal diseases, and neurological
+disorders, among others [@Scotti2018]. Large-scale analyses of cancer
+transcriptomic data, comparing tumor to normal samples, have
+identified that protein domain losses are a common feature of DTU in
+cancers, including domains involved in protein-protein interactions
+[@Vitting2017;@Climente2017].
+
 While many tutorials and workflows in the
 Bioconductor project address differential gene expression, there are
 fewer workflows for performing a differential transcript usage analysis,
@@ -153,7 +172,7 @@ the null hypothesis at the gene-level, investigators would likely
 desire to know which transcripts within a gene participated in the
 differential usage.
 
-```{r diagram, echo=FALSE, out.width="100%", fig.cap="Diagram of the methods presented in this workflow. In bold are the recommended choices for quantification and filtering Salmon transcript-level data as input to the statistical methods. The recommended DRIMSeq filters are discussed in this workflow."}
+```{r diagram, echo=FALSE, out.width="100%", fig.cap="Diagram of the methods presented in this workflow. The left-side shows two paths for performing differential transcript usage (DTU) using Bioconductor packages and the right-side shows two paths for performing differential gene expression (DGE). DTU and DGE are complementary analyses of changes in transcription across conditions. This workflow focuses mostly on DTU, as there are a number of other published Bioconductor workflows for DGE. In bold are the recommended choices for quantification and filtering Salmon transcript-level data as input to the statistical methods. The recommended DRIMSeq filters are discussed in this workflow."}
 knitr::include_graphics("figs/swimdown_diagram.png")
 ```