From 8f2db4d7dcad9429a2b007ff2a1246e68f38d53b Mon Sep 17 00:00:00 2001 From: yao-lzy <59754639+yao-lzy@users.noreply.github.com> Date: Thu, 21 Dec 2023 16:22:13 -0500 Subject: [PATCH] Delete docs directory --- docs/.DS_Store | Bin 6148 -> 0 bytes docs/01-metadata.Rmd | 52 --- docs/02-omics-data.Rmd | 39 -- docs/03-statistical-analysis-.Rmd | 33 -- docs/README.md | 2 - docs/_book/404.html | 193 -------- docs/_book/index.html | 207 --------- .../anchor-sections-hash.css | 2 - .../anchor-sections-1.1.0/anchor-sections.css | 4 - .../anchor-sections-1.1.0/anchor-sections.js | 11 - .../css/fontawesome/fontawesome-webfont.ttf | Bin 165548 -> 0 bytes .../gitbook-2.6.7/css/plugin-bookdown.css | 105 ----- .../gitbook-2.6.7/css/plugin-clipboard.css | 18 - .../gitbook-2.6.7/css/plugin-fontsettings.css | 303 ------------- .../gitbook-2.6.7/css/plugin-highlight.css | 426 ------------------ .../libs/gitbook-2.6.7/css/plugin-search.css | 31 -- .../libs/gitbook-2.6.7/css/plugin-table.css | 1 - docs/_book/libs/gitbook-2.6.7/css/style.css | 13 - docs/_book/libs/gitbook-2.6.7/js/app.min.js | 1 - .../libs/gitbook-2.6.7/js/clipboard.min.js | 7 - .../libs/gitbook-2.6.7/js/jquery.highlight.js | 86 ---- .../libs/gitbook-2.6.7/js/plugin-bookdown.js | 259 ----------- .../libs/gitbook-2.6.7/js/plugin-clipboard.js | 33 -- .../gitbook-2.6.7/js/plugin-fontsettings.js | 152 ------- .../libs/gitbook-2.6.7/js/plugin-search.js | 270 ----------- .../libs/gitbook-2.6.7/js/plugin-sharing.js | 116 ----- .../libs/jquery-3.6.0/jquery-3.6.0.min.js | 2 - docs/_book/overview-of-metadata-types.html | 235 ---------- docs/_book/overview-of-omics-data-types.html | 222 --------- ...rview-of-statistical-analysis-methods.html | 218 --------- docs/_book/reference-keys.txt | 23 - docs/_book/search_index.json | 1 - docs/_book/style.css | 14 - docs/_bookdown.yml | 4 - docs/_output.yml | 19 - docs/book.bib | 10 - docs/index.Rmd | 26 -- docs/preamble.tex | 1 - docs/style.css | 14 - 39 files changed, 3153 deletions(-) delete mode 100644 docs/.DS_Store delete mode 100644 docs/01-metadata.Rmd delete mode 100644 docs/02-omics-data.Rmd delete mode 100644 docs/03-statistical-analysis-.Rmd delete mode 100644 docs/README.md delete mode 100644 docs/_book/404.html delete mode 100644 docs/_book/index.html delete mode 100644 docs/_book/libs/anchor-sections-1.1.0/anchor-sections-hash.css delete mode 100644 docs/_book/libs/anchor-sections-1.1.0/anchor-sections.css delete mode 100644 docs/_book/libs/anchor-sections-1.1.0/anchor-sections.js delete mode 100644 docs/_book/libs/gitbook-2.6.7/css/fontawesome/fontawesome-webfont.ttf delete mode 100644 docs/_book/libs/gitbook-2.6.7/css/plugin-bookdown.css delete mode 100644 docs/_book/libs/gitbook-2.6.7/css/plugin-clipboard.css delete mode 100644 docs/_book/libs/gitbook-2.6.7/css/plugin-fontsettings.css delete mode 100644 docs/_book/libs/gitbook-2.6.7/css/plugin-highlight.css delete mode 100644 docs/_book/libs/gitbook-2.6.7/css/plugin-search.css delete mode 100644 docs/_book/libs/gitbook-2.6.7/css/plugin-table.css delete mode 100644 docs/_book/libs/gitbook-2.6.7/css/style.css delete mode 100644 docs/_book/libs/gitbook-2.6.7/js/app.min.js delete mode 100644 docs/_book/libs/gitbook-2.6.7/js/clipboard.min.js delete mode 100644 docs/_book/libs/gitbook-2.6.7/js/jquery.highlight.js delete mode 100644 docs/_book/libs/gitbook-2.6.7/js/plugin-bookdown.js delete mode 100644 docs/_book/libs/gitbook-2.6.7/js/plugin-clipboard.js delete mode 100644 docs/_book/libs/gitbook-2.6.7/js/plugin-fontsettings.js delete mode 100644 docs/_book/libs/gitbook-2.6.7/js/plugin-search.js delete mode 100644 docs/_book/libs/gitbook-2.6.7/js/plugin-sharing.js delete mode 100644 docs/_book/libs/jquery-3.6.0/jquery-3.6.0.min.js delete mode 100644 docs/_book/overview-of-metadata-types.html delete mode 100644 docs/_book/overview-of-omics-data-types.html delete mode 100644 docs/_book/overview-of-statistical-analysis-methods.html delete mode 100644 docs/_book/reference-keys.txt delete mode 100644 docs/_book/search_index.json delete mode 100644 docs/_book/style.css delete mode 100644 docs/_bookdown.yml delete mode 100644 docs/_output.yml delete mode 100644 docs/book.bib delete mode 100644 docs/index.Rmd delete mode 100644 docs/preamble.tex delete mode 100644 docs/style.css diff --git a/docs/.DS_Store b/docs/.DS_Store deleted file mode 100644 index 9712f24354127a7ed14a8c75f81022a89e6027cf..0000000000000000000000000000000000000000 GIT binary patch literal 0 HcmV?d00001 literal 6148 zcmeHKJ5Izv4D~>YAet>H=L&m+VHHl03W)-RMGI0^Sqagn;||=1p3_kC`~fA3mXZRV zCC|&)ewpMIaV#Qf^SoV)tVE=SE6R&5OVhmi!cHPm0h8XN->uubVSiXu9uFwDl3pIA zlcyQKzPX;}_CwQj{m>y+-@msXyVtkNd4Bt2{_rq)wzCW>jS5f!DnJFOz`s-gJzK3l zcjQV1r~noCRzSZG8Ln6YM@Rc~V6hPZsK4=MxVBjWm^A<_fukcLu;f&rQ&Wr>$?1sa zs4Ib^qthkX$+%CPoMJ*rb~@tO$|V&?u2g^u%oRBG?MnOq75vEjKPPcV1*pKEQXo}L z+idVk(OVZUr@c1AZ{c5tS}Vt5tr%#n7#nTH7n8cI*T|Q^(b4FL8y(0W0o8>@1%5+; EPmazi$^ZZW diff --git a/docs/01-metadata.Rmd b/docs/01-metadata.Rmd deleted file mode 100644 index 910e01f..0000000 --- a/docs/01-metadata.Rmd +++ /dev/null @@ -1,52 +0,0 @@ -# Overview of Metadata Types - -For each outcome type, include information on: - -- Overview of experimental procedures performed prior to collecting the data (and relevant technical parameters) -> refer to timeline diagram -- Glossary of every variable in the tool: what precisely does it mean, what are the units, etc -- Who collected the data (institution) -- Replicates - were there any, are they different groups of islets, different individual cells, etc -- Explanation of any changes in protocols (ie. switch to different GSIS concentrations, maybe different platform used halfway through, etc) -- Whether data was intentionally collected on specific subsets of donors -- Versions of data available for download -- Data processing prior to statistical analysis (merging replicates, transformations, removed outliers, definition of any computed/normalized values) -- Any additional notes -- Citations of papers that have published parts of the data - - -## Donor Characteristics: - -Donor characteristics are provided to the Isletcore team through the organ procurement programs. These characteristics can come from the family and aren’t always accurate reflections of the medical history. Hba1c measurements are performed in the Isletcore when the donor blood sample is available. - -## Organ Characteristics and Processing: - -Organ characteristic and processing data is recorded during the islet isolation by the lead technician. Cold Ischemia time will be calculated based on the cross clamp time during organ procurement until the start of the isolation in Edmonton. - -## Isolation Outcomes: - -Islet purity, IEQ, % trapped, IPI are determined by the lead technician. Full details on determining IEQ, purity etc can be found [here](https://www.protocols.io/view/human-islet-quantification-and-purity-assessment-14egnxxwml5d/v3/) or in our [IsletCore](http://www.bcell.org/uploads/5/1/3/3/51338649/adi_isletcore_welcome_booklet.pdf) welcome booklet. Details on determining Insulin and DNA samples can always be found [here](https://www.protocols.io/view/sampling-of-human-islets-for-quality-control-purpo-j8nlk553dl5r/v2). Cell proportion data is determined through our proteomics data. Proteomics samples are shipped to Jim Johnson’s lab at UBC. Samples are then hand picked and snap frozen for processing. - -## Cell Culture Outcomes: - -On the day of shipping, Islets are recounted to determine IEQ, % recovery, IPI after culture. Culture time is determined by the end of the isolation until approximately 9am on a shipping day. Post culture samples are collected for insulin and DNA as [previously described](https://www.protocols.io/view/sampling-of-human-islets-for-quality-control-purpo-j8nlk553dl5r/v2). - -## Static Insulin Secretion: - -In triplicates, 15 hand picked islets from each donor were sequentially treated with low glucose for 1 hour followed by high glucose 1 hour. Collected supernatant for low glucose, high glucose or insulin content are measured by ELISA and recorded in the database. For each donor, there are multiple glucose combinations that may have been used. Glucose pairs are 1mM to 10mM glucose, 1mM to 16.7mM glucose or 2.8mM glucose to 16.7mM glucose. Islets used in the 1mM to 10mM group are unique from the 1mM to 16.7mM group. The secretion data are commonly presented as a percentage of the total content (secreted insulin/total insulin *100), and as a stimulation index (high glucose secretion/low glucose secretion). Biological outliers were defined as “Seth is coming up with the definition now”, and identified outliers were removed from the dataset. The data for each replicate (after outlier removal) can be downloaded from the data export page. The total insulin content, secretion percentages, and stimulation indices, averaged across replicates, can be queried, analyzed, and visualized in the other parts of the tool. Complete experimental details can be found [here](https://www.protocols.io/view/static-glucose-stimulated-insulin-secretion-gsis-p-n2bvjkzxgk5w/v3). - - -## Islet Oxygen Consumption (Seahorse assay): - - -## Dynamic Insulin Responses to Macronutrients: - -Human islets are shipped to Jim Johnson’s lab at UBC. Islets are hand picked and cultured in RPMI for 24-72hrs before the experiment to allow the islets to recover from shipping. 65 islets are loaded per chamber and pre-incubated for 1 hour. Islets are stimulated with 6 or 15mM glucose, 5mM Leucine or 0.75mM Oleic acid/0.75mM palmitic acid as indicated. Samples are stored at -20C until analysis with RIA. Full details are described [here](https://www.medrxiv.org/content/10.1101/2023.05.24.23290298v1.full.pdf). - -## Single-cell Function (electrophysiology) - -Human islets are hand picked and dispersed into single cells and plated on 35mm cell culture dishes by the MacDonald lab. 24-72 hours after the dispersion, electrophysiological measurements are recorded. Cell identity is confirmed by immunohistochemistry. - - - - - diff --git a/docs/02-omics-data.Rmd b/docs/02-omics-data.Rmd deleted file mode 100644 index e56c21d..0000000 --- a/docs/02-omics-data.Rmd +++ /dev/null @@ -1,39 +0,0 @@ -# Overview of Omics Data Types - -For each data type, include information on: - -- Platform(s) -- Batches (and whether batch effect is significant) -- Any logistical (shipping, storage)/lab procedures conducted prior to collecting data (and indicate relevant technical parameters - ie. culture times, etc) -- Whether data was intentionally collected on specific subsets of donors -- Raw data processing pipeline -- Where you can find raw data files -- Missing value strategy, filtering, and normalization prior to statistical analysis -- Any additional notes -- Citations of papers that have published parts of the data - -## Gene expression (bulk RNA-seq) -RNA-seq profiles were collected starting in [YEAR]in batches of islets from ~10-20 donors. [Include information on batches]. Raw reads were aligned to the [BLANK GENOME] using [BLANK SOFTWARE version BLANK]. The counts matrix was filtered to remove any genes with fewer than [X] mean counts. The counts were normalized for sequencing depth and adjusted to account for high variance/high abundant genes using the [BLANK] method in the limma voom R package (version #). Batch effect was corrected using the Combat-Seq R package (version #). Since - -## Gene expression (Nanostring) -50 islets are hand picked in Edmonton. Cells are washed with PBS then collected in 100ul of RLT Beta-mercaptoethanol. Islets arestored at -80C before shipping to the Lynn Lab. - -## Protein expression (proteomics) -Human islets are shipped to Jim Johnson’s lab at UBC. 300 Islets are hand picked, washed with pbs and pellet is snap frozen and stored at -80C. Details of lysis and analysis are found [here](https://www.medrxiv.org/content/10.1101/2023.05.24.23290298v1.full.pdf). - -## Gene expression (single-cell RNA-seq) - -## Gene expression (pseudobulk RNA-seq) -150 islets are hand picked at the University of Alberta and transferred into a tube with 1ml of Trizol reagent. Samples are stored at -80C until shipping to Anna Gloyn’s lab (originally Oxford now Stanford). - - - - - - - - - - - - diff --git a/docs/03-statistical-analysis-.Rmd b/docs/03-statistical-analysis-.Rmd deleted file mode 100644 index d0e3acf..0000000 --- a/docs/03-statistical-analysis-.Rmd +++ /dev/null @@ -1,33 +0,0 @@ -# Overview of statistical analysis methods - -For each analysis, include details on: - -- Specific methods (and R packages) used for each task (aimed for statisticians/data scientists) -- Explanation of how the methods work, what they are useful for, and their limitations (aimed for biologists, not statisticians/data scientists) -- Which parameters are exposed in the interface, what they do, and rationale for which parameters were exposed -- How to interpret the results -- How to report the results (which details/citations to include in methods sections of papers) -- Any additional notes - -## Multiple linear regression - -## Spearman ranked correlation - -## Overrepresentation analysis - -## Gene set enrichment analysis - -## Pipelines to generate significant feature associations for feature search page - -## Sources of annotation files, pathway libraries, & link to code repository - - - - - - - - - - - diff --git a/docs/README.md b/docs/README.md deleted file mode 100644 index 97aa12b..0000000 --- a/docs/README.md +++ /dev/null @@ -1,2 +0,0 @@ - -This is an introduction of the Human Islet project. diff --git a/docs/_book/404.html b/docs/_book/404.html deleted file mode 100644 index c30cc0c..0000000 --- a/docs/_book/404.html +++ /dev/null @@ -1,193 +0,0 @@ - - - - - - - Page not found | Human Islets - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
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Chapter 1 General Introduction

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The HumanIslets tool houses data collected from or associated with human islets procured by the University of Alberta. The data includes clinical metadata

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I envision a branching timeline, so that you can visualize everything that happened to an islet sample prior to the collection of each data type. Here is a rough outline of steps (I know it’s incomplete/wrong - will look at some of the guides on the IsletCore website to better sketch out)

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b/docs/_book/libs/gitbook-2.6.7/css/plugin-fontsettings.css deleted file mode 100644 index 3fa6f35..0000000 --- a/docs/_book/libs/gitbook-2.6.7/css/plugin-fontsettings.css +++ /dev/null @@ -1,303 +0,0 @@ -/* - * Theme 1 - */ -.color-theme-1 .dropdown-menu { - background-color: #111111; - border-color: #7e888b; -} -.color-theme-1 .dropdown-menu .dropdown-caret .caret-inner { - border-bottom: 9px solid #111111; -} -.color-theme-1 .dropdown-menu .buttons { - border-color: #7e888b; -} -.color-theme-1 .dropdown-menu .button { - color: #afa790; -} -.color-theme-1 .dropdown-menu .button:hover { - color: #73553c; -} -/* - * Theme 2 - */ -.color-theme-2 .dropdown-menu { - background-color: #2d3143; - border-color: #272a3a; -} -.color-theme-2 .dropdown-menu .dropdown-caret .caret-inner { - border-bottom: 9px solid #2d3143; -} -.color-theme-2 .dropdown-menu .buttons { - border-color: #272a3a; -} -.color-theme-2 .dropdown-menu .button { - color: #62677f; -} -.color-theme-2 .dropdown-menu .button:hover { - color: #f4f4f5; -} -.book .book-header .font-settings .font-enlarge { - line-height: 30px; - font-size: 1.4em; -} -.book .book-header .font-settings .font-reduce { - line-height: 30px; - font-size: 1em; -} - -/* sidebar transition background */ -div.book.color-theme-1 { - background: #f3eacb; -} -.book.color-theme-1 .book-body { - color: #704214; - background: #f3eacb; -} -.book.color-theme-1 .book-body .page-wrapper .page-inner section { - background: #f3eacb; -} - -/* sidebar transition background */ -div.book.color-theme-2 { - background: #1c1f2b; -} - -.book.color-theme-2 .book-body { - color: #bdcadb; - background: #1c1f2b; -} -.book.color-theme-2 .book-body .page-wrapper .page-inner section { - background: #1c1f2b; -} -.book.font-size-0 .book-body .page-inner section { - font-size: 1.2rem; -} -.book.font-size-1 .book-body .page-inner section { - font-size: 1.4rem; -} -.book.font-size-2 .book-body .page-inner section { - font-size: 1.6rem; -} -.book.font-size-3 .book-body .page-inner section { - font-size: 2.2rem; -} -.book.font-size-4 .book-body .page-inner section { - font-size: 4rem; -} -.book.font-family-0 { - font-family: Georgia, serif; -} -.book.font-family-1 { - font-family: "Helvetica Neue", Helvetica, Arial, sans-serif; -} -.book.color-theme-1 .book-body .page-wrapper .page-inner section.normal { - color: #704214; -} -.book.color-theme-1 .book-body .page-wrapper .page-inner section.normal a { - color: inherit; -} -.book.color-theme-1 .book-body .page-wrapper .page-inner section.normal h1, -.book.color-theme-1 .book-body .page-wrapper .page-inner section.normal h2, -.book.color-theme-1 .book-body .page-wrapper .page-inner section.normal h3, -.book.color-theme-1 .book-body .page-wrapper .page-inner section.normal h4, -.book.color-theme-1 .book-body .page-wrapper .page-inner section.normal h5, -.book.color-theme-1 .book-body .page-wrapper .page-inner section.normal h6 { - color: inherit; -} -.book.color-theme-1 .book-body .page-wrapper 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section.normal table td { - border-color: #3b3f54; -} -.book.color-theme-2 .book-body .page-wrapper .page-inner section.normal table tr { - color: #b6c2d2; - background-color: #2d3143; - border-color: #3b3f54; -} -.book.color-theme-2 .book-body .page-wrapper .page-inner section.normal table tr:nth-child(2n) { - background-color: #35394b; -} -.book.color-theme-1 .book-header { - color: #afa790; - background: transparent; -} -.book.color-theme-1 .book-header .btn { - color: #afa790; -} -.book.color-theme-1 .book-header .btn:hover { - color: #73553c; - background: none; -} -.book.color-theme-1 .book-header h1 { - color: #704214; -} -.book.color-theme-2 .book-header { - color: #7e888b; - background: transparent; -} -.book.color-theme-2 .book-header .btn { - color: #3b3f54; -} -.book.color-theme-2 .book-header .btn:hover { - color: #fffff5; - background: none; -} -.book.color-theme-2 .book-header h1 { - color: #bdcadb; -} -.book.color-theme-1 .book-body .navigation { - color: #afa790; -} -.book.color-theme-1 .book-body .navigation:hover { - color: #73553c; -} -.book.color-theme-2 .book-body .navigation { - color: #383f52; -} -.book.color-theme-2 .book-body .navigation:hover { - color: #fffff5; -} -/* - * Theme 1 - */ -.book.color-theme-1 .book-summary { - color: #afa790; - background: #111111; - border-right: 1px solid rgba(0, 0, 0, 0.07); -} -.book.color-theme-1 .book-summary .book-search { - background: transparent; -} -.book.color-theme-1 .book-summary .book-search input, -.book.color-theme-1 .book-summary .book-search input:focus { - border: 1px solid transparent; -} -.book.color-theme-1 .book-summary ul.summary li.divider { - background: #7e888b; - box-shadow: none; -} -.book.color-theme-1 .book-summary ul.summary li i.fa-check { - color: #33cc33; -} -.book.color-theme-1 .book-summary ul.summary li.done > a { - color: #877f6a; -} -.book.color-theme-1 .book-summary ul.summary li a, -.book.color-theme-1 .book-summary ul.summary li span { - color: #877f6a; - 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nt:"\f083"}.fa-key:before{content:"\f084"}.fa-gears:before,.fa-cogs:before{content:"\f085"}.fa-comments:before{content:"\f086"}.fa-thumbs-o-up:before{content:"\f087"}.fa-thumbs-o-down:before{content:"\f088"}.fa-star-half:before{content:"\f089"}.fa-heart-o:before{content:"\f08a"}.fa-sign-out:before{content:"\f08b"}.fa-linkedin-square:before{content:"\f08c"}.fa-thumb-tack:before{content:"\f08d"}.fa-external-link:before{content:"\f08e"}.fa-sign-in:before{content:"\f090"}.fa-trophy:before{content:"\f091"}.fa-github-square:before{content:"\f092"}.fa-upload:before{content:"\f093"}.fa-lemon-o:before{content:"\f094"}.fa-phone:before{content:"\f095"}.fa-square-o:before{content:"\f096"}.fa-bookmark-o:before{content:"\f097"}.fa-phone-square:before{content:"\f098"}.fa-twitter:before{content:"\f099"}.fa-facebook-f:before,.fa-facebook:before{content:"\f09a"}.fa-github:before{content:"\f09b"}.fa-unlock:before{content:"\f09c"}.fa-credit-card:before{content:"\f09d"}.fa-feed:before,.fa-rss:before{content:"\f09e"}.fa-hdd-o:before{content:"\f0a0"}.fa-bullhorn:before{content:"\f0a1"}.fa-bell:before{content:"\f0f3"}.fa-certificate:before{content:"\f0a3"}.fa-hand-o-right:before{content:"\f0a4"}.fa-hand-o-left:before{content:"\f0a5"}.fa-hand-o-up:before{content:"\f0a6"}.fa-hand-o-down:before{content:"\f0a7"}.fa-arrow-circle-left:before{content:"\f0a8"}.fa-arrow-circle-right:before{content:"\f0a9"}.fa-arrow-circle-up:before{content:"\f0aa"}.fa-arrow-circle-down:before{content:"\f0ab"}.fa-globe:before{content:"\f0ac"}.fa-wrench:before{content:"\f0ad"}.fa-tasks:before{content:"\f0ae"}.fa-filter:before{content:"\f0b0"}.fa-briefcase:before{content:"\f0b1"}.fa-arrows-alt:before{content:"\f0b2"}.fa-group:before,.fa-users:before{content:"\f0c0"}.fa-chain:before,.fa-link:before{content:"\f0c1"}.fa-cloud:before{content:"\f0c2"}.fa-flask:before{content:"\f0c3"}.fa-cut:before,.fa-scissors:before{content:"\f0c4"}.fa-copy:before,.fa-files-o:before{content:"\f0c5"}.fa-paperclip:before{content:"\f0c6"}.fa-save:before,.fa-floppy-o:before{content:"\f0c7"}.fa-square:before{content:"\f0c8"}.fa-navicon:before,.fa-reorder:before,.fa-bars:before{content:"\f0c9"}.fa-list-ul:before{content:"\f0ca"}.fa-list-ol:before{content:"\f0cb"}.fa-strikethrough:before{content:"\f0cc"}.fa-underline:before{content:"\f0cd"}.fa-table:before{content:"\f0ce"}.fa-magic:before{content:"\f0d0"}.fa-truck:before{content:"\f0d1"}.fa-pinterest:before{content:"\f0d2"}.fa-pinterest-square:before{content:"\f0d3"}.fa-google-plus-square:before{content:"\f0d4"}.fa-google-plus:before{content:"\f0d5"}.fa-money:before{content:"\f0d6"}.fa-caret-down:before{content:"\f0d7"}.fa-caret-up:before{content:"\f0d8"}.fa-caret-left:before{content:"\f0d9"}.fa-caret-right:before{content:"\f0da"}.fa-columns:before{content:"\f0db"}.fa-unsorted:before,.fa-sort:before{content:"\f0dc"}.fa-sort-down:before,.fa-sort-desc:before{content:"\f0dd"}.fa-sort-up:before,.fa-sort-asc:before{content:"\f0de"}.fa-envelope:before{content:"\f0e0"}.fa-linkedin:before{content:"\f0e1"}.fa-rotate-left:before,.fa-undo:before{content:"\f0e2"}.fa-legal:before,.fa-gavel:before{content:"\f0e3"}.fa-dashboard:before,.fa-tachometer:before{content:"\f0e4"}.fa-comment-o:before{content:"\f0e5"}.fa-comments-o:before{content:"\f0e6"}.fa-flash:before,.fa-bolt:before{content:"\f0e7"}.fa-sitemap:before{content:"\f0e8"}.fa-umbrella:before{content:"\f0e9"}.fa-paste:before,.fa-clipboard:before{content:"\f0ea"}.fa-lightbulb-o:before{content:"\f0eb"}.fa-exchange:before{content:"\f0ec"}.fa-cloud-download:before{content:"\f0ed"}.fa-cloud-upload:before{content:"\f0ee"}.fa-user-md:before{content:"\f0f0"}.fa-stethoscope:before{content:"\f0f1"}.fa-suitcase:before{content:"\f0f2"}.fa-bell-o:before{content:"\f0a2"}.fa-coffee:before{content:"\f0f4"}.fa-cutlery:before{content:"\f0f5"}.fa-file-text-o:before{content:"\f0f6"}.fa-building-o:before{content:"\f0f7"}.fa-hospital-o:before{content:"\f0f8"}.fa-ambulance:before{content:"\f0f9"}.fa-medkit:before{content:"\f0fa"}.fa-fighter-jet:before{content:"\f0fb"}.fa-beer:before{content:"\f0fc"}.fa-h-square:before{content:"\f0fd"}.fa-plus-square:before{content:"\f0fe"}.fa-angle-double-left:before{content:"\f100"}.fa-angle-double-right:before{content:"\f101"}.fa-angle-double-up:before{content:"\f102"}.fa-angle-double-down:before{content:"\f103"}.fa-angle-left:before{content:"\f104"}.fa-angle-right:before{content:"\f105"}.fa-angle-up:before{content:"\f106"}.fa-angle-down:before{content:"\f107"}.fa-desktop:before{content:"\f108"}.fa-laptop:before{content:"\f109"}.fa-tablet:before{content:"\f10a"}.fa-mobile-phone:before,.fa-mobile:before{content:"\f10b"}.fa-circle-o:before{content:"\f10c"}.fa-quote-left:before{content:"\f10d"}.fa-quote-right:before{content:"\f10e"}.fa-spinner:before{content:"\f110"}.fa-circle:before{content:"\f111"}.fa-mail-reply:before,.fa-reply:before{content:"\f112"}.fa-github-alt:before{content:"\f113"}.fa-folder-o:before{content:"\f114"}.fa-folder-open-o:before{content:"\f115"}.fa-smile-o:before{c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isObj=isObject(source),props=isObj?keys(source):undefined,methodNames=props&&props.length?baseFunctions(source,props):undefined;if(!(methodNames?methodNames.length:isObj)){methodNames=false;options=source;source=object;object=this}}if(!methodNames){methodNames=baseFunctions(source,keys(source))}var chain=true,index=-1,isFunc=isFunction(object),length=methodNames.length;if(options===false){chain=false}else if(isObject(options)&&"chain"in options){chain=options.chain}while(++index0||end<0)){return new LazyWrapper(result)}if(start<0){result=result.takeRight(-start)}else if(start){result=result.drop(start)}if(end!==undefined){end=+end||0;result=end<0?result.dropRight(-end):result.take(end-start)}return result};LazyWrapper.prototype.takeRightWhile=function(predicate,thisArg){return this.reverse().takeWhile(predicate,thisArg).reverse()};LazyWrapper.prototype.toArray=function(){return this.take(POSITIVE_INFINITY)};baseForOwn(LazyWrapper.prototype,function(func,methodName){var 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if(freeExports&&freeModule){if(moduleExports){(freeModule.exports=_)._=_}else{freeExports._=_}}else{root._=_}}).call(this)}).call(this,typeof global!=="undefined"?global:typeof self!=="undefined"?self:typeof window!=="undefined"?window:{})},{}],3:[function(require,module,exports){(function(window,document,undefined){var _MAP={8:"backspace",9:"tab",13:"enter",16:"shift",17:"ctrl",18:"alt",20:"capslock",27:"esc",32:"space",33:"pageup",34:"pagedown",35:"end",36:"home",37:"left",38:"up",39:"right",40:"down",45:"ins",46:"del",91:"meta",93:"meta",224:"meta"};var _KEYCODE_MAP={106:"*",107:"+",109:"-",110:".",111:"/",186:";",187:"=",188:",",189:"-",190:".",191:"/",192:"`",219:"[",220:"\\",221:"]",222:"'"};var _SHIFT_MAP={"~":"`","!":"1","@":"2","#":"3",$:"4","%":"5","^":"6","&":"7","*":"8","(":"9",")":"0",_:"-","+":"=",":":";",'"':"'","<":",",">":".","?":"/","|":"\\"};var _SPECIAL_ALIASES={option:"alt",command:"meta",return:"enter",escape:"esc",plus:"+",mod:/Mac|iPod|iPhone|iPad/.test(navigator.platform)?"meta":"ctrl"};var _REVERSE_MAP;for(var i=1;i<20;++i){_MAP[111+i]="f"+i}for(i=0;i<=9;++i){_MAP[i+96]=i}function _addEvent(object,type,callback){if(object.addEventListener){object.addEventListener(type,callback,false);return}object.attachEvent("on"+type,callback)}function _characterFromEvent(e){if(e.type=="keypress"){var character=String.fromCharCode(e.which);if(!e.shiftKey){character=character.toLowerCase()}return character}if(_MAP[e.which]){return _MAP[e.which]}if(_KEYCODE_MAP[e.which]){return _KEYCODE_MAP[e.which]}return String.fromCharCode(e.which).toLowerCase()}function _modifiersMatch(modifiers1,modifiers2){return modifiers1.sort().join(",")===modifiers2.sort().join(",")}function _eventModifiers(e){var modifiers=[];if(e.shiftKey){modifiers.push("shift")}if(e.altKey){modifiers.push("alt")}if(e.ctrlKey){modifiers.push("ctrl")}if(e.metaKey){modifiers.push("meta")}return modifiers}function _preventDefault(e){if(e.preventDefault){e.preventDefault();return}e.returnValue=false}function _stopPropagation(e){if(e.stopPropagation){e.stopPropagation();return}e.cancelBubble=true}function _isModifier(key){return key=="shift"||key=="ctrl"||key=="alt"||key=="meta"}function _getReverseMap(){if(!_REVERSE_MAP){_REVERSE_MAP={};for(var key in _MAP){if(key>95&&key<112){continue}if(_MAP.hasOwnProperty(key)){_REVERSE_MAP[_MAP[key]]=key}}}return _REVERSE_MAP}function _pickBestAction(key,modifiers,action){if(!action){action=_getReverseMap()[key]?"keydown":"keypress"}if(action=="keypress"&&modifiers.length){action="keydown"}return action}function _keysFromString(combination){if(combination==="+"){return["+"]}combination=combination.replace(/\+{2}/g,"+plus");return combination.split("+")}function _getKeyInfo(combination,action){var keys;var key;var i;var modifiers=[];keys=_keysFromString(combination);for(i=0;i1){_bindSequence(combination,sequence,callback,action);return}info=_getKeyInfo(combination,action);self._callbacks[info.key]=self._callbacks[info.key]||[];_getMatches(info.key,info.modifiers,{type:info.action},sequenceName,combination,level);self._callbacks[info.key][sequenceName?"unshift":"push"]({callback:callback,modifiers:info.modifiers,action:info.action,seq:sequenceName,level:level,combo:combination})}self._bindMultiple=function(combinations,callback,action){for(var i=0;i-1){return false}if(_belongsTo(element,self.target)){return false}return element.tagName=="INPUT"||element.tagName=="SELECT"||element.tagName=="TEXTAREA"||element.isContentEditable};Mousetrap.prototype.handleKey=function(){var self=this;return self._handleKey.apply(self,arguments)};Mousetrap.init=function(){var documentMousetrap=Mousetrap(document);for(var method in documentMousetrap){if(method.charAt(0)!=="_"){Mousetrap[method]=function(method){return function(){return documentMousetrap[method].apply(documentMousetrap,arguments)}}(method)}}};Mousetrap.init();window.Mousetrap=Mousetrap;if(typeof module!=="undefined"&&module.exports){module.exports=Mousetrap}if(typeof define==="function"&&define.amd){define(function(){return Mousetrap})}})(window,document)},{}],4:[function(require,module,exports){(function(process){function normalizeArray(parts,allowAboveRoot){var up=0;for(var i=parts.length-1;i>=0;i--){var last=parts[i];if(last==="."){parts.splice(i,1)}else if(last===".."){parts.splice(i,1);up++}else if(up){parts.splice(i,1);up--}}if(allowAboveRoot){for(;up--;up){parts.unshift("..")}}return parts}var splitPathRe=/^(\/?|)([\s\S]*?)((?:\.{1,2}|[^\/]+?|)(\.[^.\/]*|))(?:[\/]*)$/;var splitPath=function(filename){return splitPathRe.exec(filename).slice(1)};exports.resolve=function(){var resolvedPath="",resolvedAbsolute=false;for(var i=arguments.length-1;i>=-1&&!resolvedAbsolute;i--){var path=i>=0?arguments[i]:process.cwd();if(typeof path!=="string"){throw new TypeError("Arguments to path.resolve must be strings")}else if(!path){continue}resolvedPath=path+"/"+resolvedPath;resolvedAbsolute=path.charAt(0)==="/"}resolvedPath=normalizeArray(filter(resolvedPath.split("/"),function(p){return!!p}),!resolvedAbsolute).join("/");return(resolvedAbsolute?"/":"")+resolvedPath||"."};exports.normalize=function(path){var isAbsolute=exports.isAbsolute(path),trailingSlash=substr(path,-1)==="/";path=normalizeArray(filter(path.split("/"),function(p){return!!p}),!isAbsolute).join("/");if(!path&&!isAbsolute){path="."}if(path&&trailingSlash){path+="/"}return(isAbsolute?"/":"")+path};exports.isAbsolute=function(path){return path.charAt(0)==="/"};exports.join=function(){var paths=Array.prototype.slice.call(arguments,0);return exports.normalize(filter(paths,function(p,index){if(typeof p!=="string"){throw new TypeError("Arguments to path.join must be strings")}return p}).join("/"))};exports.relative=function(from,to){from=exports.resolve(from).substr(1);to=exports.resolve(to).substr(1);function trim(arr){var start=0;for(;start=0;end--){if(arr[end]!=="")break}if(start>end)return[];return arr.slice(start,end-start+1)}var fromParts=trim(from.split("/"));var toParts=trim(to.split("/"));var length=Math.min(fromParts.length,toParts.length);var samePartsLength=length;for(var i=0;i1){for(var i=1;i= 0x80 (not a basic code point)","invalid-input":"Invalid input"},baseMinusTMin=base-tMin,floor=Math.floor,stringFromCharCode=String.fromCharCode,key;function error(type){throw RangeError(errors[type])}function map(array,fn){var length=array.length;var result=[];while(length--){result[length]=fn(array[length])}return result}function mapDomain(string,fn){var parts=string.split("@");var result="";if(parts.length>1){result=parts[0]+"@";string=parts[1]}string=string.replace(regexSeparators,".");var labels=string.split(".");var encoded=map(labels,fn).join(".");return result+encoded}function ucs2decode(string){var output=[],counter=0,length=string.length,value,extra;while(counter=55296&&value<=56319&&counter65535){value-=65536;output+=stringFromCharCode(value>>>10&1023|55296);value=56320|value&1023}output+=stringFromCharCode(value);return output}).join("")}function basicToDigit(codePoint){if(codePoint-48<10){return codePoint-22}if(codePoint-65<26){return codePoint-65}if(codePoint-97<26){return codePoint-97}return base}function digitToBasic(digit,flag){return digit+22+75*(digit<26)-((flag!=0)<<5)}function adapt(delta,numPoints,firstTime){var k=0;delta=firstTime?floor(delta/damp):delta>>1;delta+=floor(delta/numPoints);for(;delta>baseMinusTMin*tMax>>1;k+=base){delta=floor(delta/baseMinusTMin)}return floor(k+(baseMinusTMin+1)*delta/(delta+skew))}function decode(input){var output=[],inputLength=input.length,out,i=0,n=initialN,bias=initialBias,basic,j,index,oldi,w,k,digit,t,baseMinusT;basic=input.lastIndexOf(delimiter);if(basic<0){basic=0}for(j=0;j=128){error("not-basic")}output.push(input.charCodeAt(j))}for(index=basic>0?basic+1:0;index=inputLength){error("invalid-input")}digit=basicToDigit(input.charCodeAt(index++));if(digit>=base||digit>floor((maxInt-i)/w)){error("overflow")}i+=digit*w;t=k<=bias?tMin:k>=bias+tMax?tMax:k-bias;if(digitfloor(maxInt/baseMinusT)){error("overflow")}w*=baseMinusT}out=output.length+1;bias=adapt(i-oldi,out,oldi==0);if(floor(i/out)>maxInt-n){error("overflow")}n+=floor(i/out);i%=out;output.splice(i++,0,n)}return ucs2encode(output)}function encode(input){var n,delta,handledCPCount,basicLength,bias,j,m,q,k,t,currentValue,output=[],inputLength,handledCPCountPlusOne,baseMinusT,qMinusT;input=ucs2decode(input);inputLength=input.length;n=initialN;delta=0;bias=initialBias;for(j=0;j=n&¤tValuefloor((maxInt-delta)/handledCPCountPlusOne)){error("overflow")}delta+=(m-n)*handledCPCountPlusOne;n=m;for(j=0;jmaxInt){error("overflow")}if(currentValue==n){for(q=delta,k=base;;k+=base){t=k<=bias?tMin:k>=bias+tMax?tMax:k-bias;if(q0&&len>maxKeys){len=maxKeys}for(var i=0;i=0){kstr=x.substr(0,idx);vstr=x.substr(idx+1)}else{kstr=x;vstr=""}k=decodeURIComponent(kstr);v=decodeURIComponent(vstr);if(!hasOwnProperty(obj,k)){obj[k]=v}else if(isArray(obj[k])){obj[k].push(v)}else{obj[k]=[obj[k],v]}}return obj};var isArray=Array.isArray||function(xs){return Object.prototype.toString.call(xs)==="[object Array]"}},{}],8:[function(require,module,exports){"use strict";var stringifyPrimitive=function(v){switch(typeof v){case"string":return v;case"boolean":return v?"true":"false";case"number":return isFinite(v)?v:"";default:return""}};module.exports=function(obj,sep,eq,name){sep=sep||"&";eq=eq||"=";if(obj===null){obj=undefined}if(typeof obj==="object"){return map(objectKeys(obj),function(k){var ks=encodeURIComponent(stringifyPrimitive(k))+eq;if(isArray(obj[k])){return map(obj[k],function(v){return ks+encodeURIComponent(stringifyPrimitive(v))}).join(sep)}else{return ks+encodeURIComponent(stringifyPrimitive(obj[k]))}}).join(sep)}if(!name)return"";return encodeURIComponent(stringifyPrimitive(name))+eq+encodeURIComponent(stringifyPrimitive(obj))};var isArray=Array.isArray||function(xs){return Object.prototype.toString.call(xs)==="[object Array]"};function map(xs,f){if(xs.map)return xs.map(f);var res=[];for(var i=0;i",'"',"`"," ","\r","\n","\t"],unwise=["{","}","|","\\","^","`"].concat(delims),autoEscape=["'"].concat(unwise),nonHostChars=["%","/","?",";","#"].concat(autoEscape),hostEndingChars=["/","?","#"],hostnameMaxLen=255,hostnamePartPattern=/^[a-z0-9A-Z_-]{0,63}$/,hostnamePartStart=/^([a-z0-9A-Z_-]{0,63})(.*)$/,unsafeProtocol={javascript:true,"javascript:":true},hostlessProtocol={javascript:true,"javascript:":true},slashedProtocol={http:true,https:true,ftp:true,gopher:true,file:true,"http:":true,"https:":true,"ftp:":true,"gopher:":true,"file:":true},querystring=require("querystring");function urlParse(url,parseQueryString,slashesDenoteHost){if(url&&isObject(url)&&url instanceof Url)return url;var u=new Url;u.parse(url,parseQueryString,slashesDenoteHost);return u}Url.prototype.parse=function(url,parseQueryString,slashesDenoteHost){if(!isString(url)){throw new TypeError("Parameter 'url' must be a string, not "+typeof url)}var rest=url;rest=rest.trim();var proto=protocolPattern.exec(rest);if(proto){proto=proto[0];var lowerProto=proto.toLowerCase();this.protocol=lowerProto;rest=rest.substr(proto.length)}if(slashesDenoteHost||proto||rest.match(/^\/\/[^@\/]+@[^@\/]+/)){var slashes=rest.substr(0,2)==="//";if(slashes&&!(proto&&hostlessProtocol[proto])){rest=rest.substr(2);this.slashes=true}}if(!hostlessProtocol[proto]&&(slashes||proto&&!slashedProtocol[proto])){var hostEnd=-1;for(var i=0;i127){newpart+="x"}else{newpart+=part[j]}}if(!newpart.match(hostnamePartPattern)){var validParts=hostparts.slice(0,i);var notHost=hostparts.slice(i+1);var bit=part.match(hostnamePartStart);if(bit){validParts.push(bit[1]);notHost.unshift(bit[2])}if(notHost.length){rest="/"+notHost.join(".")+rest}this.hostname=validParts.join(".");break}}}}if(this.hostname.length>hostnameMaxLen){this.hostname=""}else{this.hostname=this.hostname.toLowerCase()}if(!ipv6Hostname){var domainArray=this.hostname.split(".");var newOut=[];for(var i=0;i0?result.host.split("@"):false;if(authInHost){result.auth=authInHost.shift();result.host=result.hostname=authInHost.shift()}}result.search=relative.search;result.query=relative.query;if(!isNull(result.pathname)||!isNull(result.search)){result.path=(result.pathname?result.pathname:"")+(result.search?result.search:"")}result.href=result.format();return result}if(!srcPath.length){result.pathname=null;if(result.search){result.path="/"+result.search}else{result.path=null}result.href=result.format();return result}var last=srcPath.slice(-1)[0];var hasTrailingSlash=(result.host||relative.host)&&(last==="."||last==="..")||last==="";var up=0;for(var i=srcPath.length;i>=0;i--){last=srcPath[i];if(last=="."){srcPath.splice(i,1)}else if(last===".."){srcPath.splice(i,1);up++}else if(up){srcPath.splice(i,1);up--}}if(!mustEndAbs&&!removeAllDots){for(;up--;up){srcPath.unshift("..")}}if(mustEndAbs&&srcPath[0]!==""&&(!srcPath[0]||srcPath[0].charAt(0)!=="/")){srcPath.unshift("")}if(hasTrailingSlash&&srcPath.join("/").substr(-1)!=="/"){srcPath.push("")}var isAbsolute=srcPath[0]===""||srcPath[0]&&srcPath[0].charAt(0)==="/";if(psychotic){result.hostname=result.host=isAbsolute?"":srcPath.length?srcPath.shift():"";var authInHost=result.host&&result.host.indexOf("@")>0?result.host.split("@"):false;if(authInHost){result.auth=authInHost.shift();result.host=result.hostname=authInHost.shift()}}mustEndAbs=mustEndAbs||result.host&&srcPath.length;if(mustEndAbs&&!isAbsolute){srcPath.unshift("")}if(!srcPath.length){result.pathname=null;result.path=null}else{result.pathname=srcPath.join("/")}if(!isNull(result.pathname)||!isNull(result.search)){result.path=(result.pathname?result.pathname:"")+(result.search?result.search:"")}result.auth=relative.auth||result.auth;result.slashes=result.slashes||relative.slashes;result.href=result.format();return result};Url.prototype.parseHost=function(){var host=this.host;var port=portPattern.exec(host);if(port){port=port[0];if(port!==":"){this.port=port.substr(1)}host=host.substr(0,host.length-port.length)}if(host)this.hostname=host};function isString(arg){return typeof arg==="string"}function isObject(arg){return typeof arg==="object"&&arg!==null}function isNull(arg){return arg===null}function isNullOrUndefined(arg){return arg==null}},{punycode:6,querystring:9}],11:[function(require,module,exports){var $=require("jquery");function toggleDropdown(e){var $dropdown=$(e.currentTarget).parent().find(".dropdown-menu");$dropdown.toggleClass("open");e.stopPropagation();e.preventDefault()}function closeDropdown(e){$(".dropdown-menu").removeClass("open")}function init(){$(document).on("click",".toggle-dropdown",toggleDropdown);$(document).on("click",".dropdown-menu",function(e){e.stopPropagation()});$(document).on("click",closeDropdown)}module.exports={init:init}},{jquery:1}],12:[function(require,module,exports){var $=require("jquery");module.exports=$({})},{jquery:1}],13:[function(require,module,exports){var $=require("jquery");var _=require("lodash");var storage=require("./storage");var dropdown=require("./dropdown");var events=require("./events");var state=require("./state");var keyboard=require("./keyboard");var navigation=require("./navigation");var sidebar=require("./sidebar");var toolbar=require("./toolbar");function start(config){sidebar.init();keyboard.init();dropdown.init();navigation.init();toolbar.createButton({index:0,icon:"fa fa-align-justify",label:"Toggle Sidebar",onClick:function(e){e.preventDefault();sidebar.toggle()}});events.trigger("start",config);navigation.notify()}var gitbook={start:start,events:events,state:state,toolbar:toolbar,sidebar:sidebar,storage:storage,keyboard:keyboard};var MODULES={gitbook:gitbook,jquery:$,lodash:_};window.gitbook=gitbook;window.$=$;window.jQuery=$;gitbook.require=function(mods,fn){mods=_.map(mods,function(mod){mod=mod.toLowerCase();if(!MODULES[mod]){throw new Error("GitBook module "+mod+" doesn't exist")}return MODULES[mod]});fn.apply(null,mods)};module.exports={}},{"./dropdown":11,"./events":12,"./keyboard":14,"./navigation":16,"./sidebar":18,"./state":19,"./storage":20,"./toolbar":21,jquery:1,lodash:2}],14:[function(require,module,exports){var Mousetrap=require("mousetrap");var navigation=require("./navigation");var sidebar=require("./sidebar");function bindShortcut(keys,fn){Mousetrap.bind(keys,function(e){fn();return false})}function init(){bindShortcut(["right"],function(e){navigation.goNext()});bindShortcut(["left"],function(e){navigation.goPrev()});bindShortcut(["s"],function(e){sidebar.toggle()})}module.exports={init:init,bind:bindShortcut}},{"./navigation":16,"./sidebar":18,mousetrap:3}],15:[function(require,module,exports){var state=require("./state");function showLoading(p){state.$book.addClass("is-loading");p.always(function(){state.$book.removeClass("is-loading")});return p}module.exports={show:showLoading}},{"./state":19}],16:[function(require,module,exports){var $=require("jquery");var url=require("url");var events=require("./events");var state=require("./state");var loading=require("./loading");var usePushState=typeof history.pushState!=="undefined";function handleNavigation(relativeUrl,push){var uri=url.resolve(window.location.pathname,relativeUrl);notifyPageChange();location.href=relativeUrl;return}function updateNavigationPosition(){var bodyInnerWidth,pageWrapperWidth;bodyInnerWidth=parseInt($(".body-inner").css("width"),10);pageWrapperWidth=parseInt($(".page-wrapper").css("width"),10);$(".navigation-next").css("margin-right",bodyInnerWidth-pageWrapperWidth+"px")}function notifyPageChange(){events.trigger("page.change")}function preparePage(notify){var $bookBody=$(".book-body");var $bookInner=$bookBody.find(".body-inner");var $pageWrapper=$bookInner.find(".page-wrapper");updateNavigationPosition();$bookInner.scrollTop(0);$bookBody.scrollTop(0);if(notify!==false)notifyPageChange()}function isLeftClickEvent(e){return e.button===0}function isModifiedEvent(e){return!!(e.metaKey||e.altKey||e.ctrlKey||e.shiftKey)}function handlePagination(e){if(isModifiedEvent(e)||!isLeftClickEvent(e)){return}e.stopPropagation();e.preventDefault();var url=$(this).attr("href");if(url)handleNavigation(url,true)}function goNext(){var url=$(".navigation-next").attr("href");if(url)handleNavigation(url,true)}function goPrev(){var url=$(".navigation-prev").attr("href");if(url)handleNavigation(url,true)}function init(){$.ajaxSetup({});if(location.protocol!=="file:"){history.replaceState({path:window.location.href},"")}window.onpopstate=function(event){if(event.state===null){return}return handleNavigation(event.state.path,false)};$(document).on("click",".navigation-prev",handlePagination);$(document).on("click",".navigation-next",handlePagination);$(document).on("click",".summary [data-path] a",handlePagination);$(window).resize(updateNavigationPosition);preparePage(false)}module.exports={init:init,goNext:goNext,goPrev:goPrev,notify:notifyPageChange}},{"./events":12,"./loading":15,"./state":19,jquery:1,url:10}],17:[function(require,module,exports){module.exports={isMobile:function(){return document.body.clientWidth<=600}}},{}],18:[function(require,module,exports){var $=require("jquery");var _=require("lodash");var storage=require("./storage");var platform=require("./platform");var state=require("./state");function toggleSidebar(_state,animation){if(state!=null&&isOpen()==_state)return;if(animation==null)animation=true;state.$book.toggleClass("without-animation",!animation);state.$book.toggleClass("with-summary",_state);storage.set("sidebar",isOpen())}function isOpen(){return state.$book.hasClass("with-summary")}function init(){if(platform.isMobile()){toggleSidebar(false,false)}else{toggleSidebar(storage.get("sidebar",true),false)}$(document).on("click",".book-summary li.chapter a",function(e){if(platform.isMobile())toggleSidebar(false,false)})}function filterSummary(paths){var $summary=$(".book-summary");$summary.find("li").each(function(){var path=$(this).data("path");var st=paths==null||_.contains(paths,path);$(this).toggle(st);if(st)$(this).parents("li").show()})}module.exports={init:init,isOpen:isOpen,toggle:toggleSidebar,filter:filterSummary}},{"./platform":17,"./state":19,"./storage":20,jquery:1,lodash:2}],19:[function(require,module,exports){var $=require("jquery");var url=require("url");var path=require("path");var state={};state.update=function(dom){var $book=$(dom.find(".book"));state.$book=$book;state.level=$book.data("level");state.basePath=$book.data("basepath");state.innerLanguage=$book.data("innerlanguage");state.revision=$book.data("revision");state.filepath=$book.data("filepath");state.chapterTitle=$book.data("chapter-title");state.root=url.resolve(location.protocol+"//"+location.host,path.dirname(path.resolve(location.pathname.replace(/\/$/,"/index.html"),state.basePath))).replace(/\/?$/,"/");state.bookRoot=state.innerLanguage?url.resolve(state.root,".."):state.root};state.update($);module.exports=state},{jquery:1,path:4,url:10}],20:[function(require,module,exports){var baseKey="";module.exports={setBaseKey:function(key){baseKey=key},set:function(key,value){key=baseKey+":"+key;try{sessionStorage[key]=JSON.stringify(value)}catch(e){}},get:function(key,def){key=baseKey+":"+key;if(sessionStorage[key]===undefined)return def;try{var v=JSON.parse(sessionStorage[key]);return v==null?def:v}catch(err){return 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",{class:"buttons"});var sizeClass="size-"+group.length;_.each(group,function(btn){btn=_.defaults(btn||{},{text:"",className:"",onClick:defaultOnClick});var $btn=$("'; - var clipboard; - - gitbook.events.bind("page.change", function() { - - if (!ClipboardJS.isSupported()) return; - - // the page.change event is thrown twice: before and after the page changes - if (clipboard) { - // clipboard is already defined but we are on the same page - if (clipboard._prevPage === window.location.pathname) return; - // clipboard is already defined and url path change - // we can deduct that we are before page changes - clipboard.destroy(); // destroy the previous events listeners - clipboard = undefined; // reset the clipboard object - return; - } - - $(copyButton).prependTo("div.sourceCode"); - - clipboard = new ClipboardJS(".copy-to-clipboard-button", { - text: function(trigger) { - return trigger.parentNode.textContent; - } - }); - - clipboard._prevPage = window.location.pathname - - }); - -}); diff --git a/docs/_book/libs/gitbook-2.6.7/js/plugin-fontsettings.js b/docs/_book/libs/gitbook-2.6.7/js/plugin-fontsettings.js deleted file mode 100644 index a70f0fb..0000000 --- a/docs/_book/libs/gitbook-2.6.7/js/plugin-fontsettings.js +++ /dev/null @@ -1,152 +0,0 @@ -gitbook.require(["gitbook", "lodash", "jQuery"], function(gitbook, _, $) { - var fontState; - - var THEMES = { - "white": 0, - "sepia": 1, - "night": 2 - }; - - var FAMILY = { - "serif": 0, - "sans": 1 - }; - - // Save current font settings - function saveFontSettings() { - gitbook.storage.set("fontState", fontState); - update(); - } - - // Increase font size - function enlargeFontSize(e) { - e.preventDefault(); - if (fontState.size >= 4) return; - - fontState.size++; - saveFontSettings(); - }; - - // Decrease font size - function reduceFontSize(e) { - e.preventDefault(); - if (fontState.size <= 0) return; - - fontState.size--; - saveFontSettings(); - }; - - // Change font family - function changeFontFamily(index, e) { - e.preventDefault(); - - fontState.family = index; - saveFontSettings(); - }; - - // Change type of color - function changeColorTheme(index, e) { - e.preventDefault(); - - var $book = $(".book"); - - if (fontState.theme !== 0) - $book.removeClass("color-theme-"+fontState.theme); - - fontState.theme = index; - if (fontState.theme !== 0) - $book.addClass("color-theme-"+fontState.theme); - - saveFontSettings(); - }; - - function update() { - var $book = gitbook.state.$book; - - $(".font-settings .font-family-list li").removeClass("active"); - $(".font-settings .font-family-list li:nth-child("+(fontState.family+1)+")").addClass("active"); - - $book[0].className = $book[0].className.replace(/\bfont-\S+/g, ''); - $book.addClass("font-size-"+fontState.size); - $book.addClass("font-family-"+fontState.family); - - if(fontState.theme !== 0) { - $book[0].className = $book[0].className.replace(/\bcolor-theme-\S+/g, ''); - $book.addClass("color-theme-"+fontState.theme); - } - }; - - function init(config) { - var $bookBody, $book; - - //Find DOM elements. - $book = gitbook.state.$book; - $bookBody = $book.find(".book-body"); - - // Instantiate font state object - fontState = gitbook.storage.get("fontState", { - size: config.size || 2, - family: FAMILY[config.family || "sans"], - theme: THEMES[config.theme || "white"] - }); - - update(); - }; - - - gitbook.events.bind("start", function(e, config) { - var opts = config.fontsettings; - if (!opts) return; - - // Create buttons in toolbar - gitbook.toolbar.createButton({ - icon: 'fa fa-font', - label: 'Font Settings', - className: 'font-settings', - dropdown: [ - [ - { - text: 'A', - className: 'font-reduce', - onClick: reduceFontSize - }, - { - text: 'A', - className: 'font-enlarge', - onClick: enlargeFontSize - } - ], - [ - { - text: 'Serif', - onClick: _.partial(changeFontFamily, 0) - }, - { - text: 'Sans', - onClick: _.partial(changeFontFamily, 1) - } - ], - [ - { - text: 'White', - onClick: _.partial(changeColorTheme, 0) - }, - { - text: 'Sepia', - onClick: _.partial(changeColorTheme, 1) - }, - { - text: 'Night', - onClick: _.partial(changeColorTheme, 2) - } - ] - ] - }); - - - // Init current settings - init(opts); - }); -}); - - diff --git a/docs/_book/libs/gitbook-2.6.7/js/plugin-search.js b/docs/_book/libs/gitbook-2.6.7/js/plugin-search.js deleted file mode 100644 index 747fcce..0000000 --- a/docs/_book/libs/gitbook-2.6.7/js/plugin-search.js +++ /dev/null @@ -1,270 +0,0 @@ -gitbook.require(["gitbook", "lodash", "jQuery"], function(gitbook, _, $) { - var index = null; - var fuse = null; - var _search = {engine: 'lunr', opts: {}}; - var $searchInput, $searchLabel, $searchForm; - var $highlighted = [], hi, hiOpts = { className: 'search-highlight' }; - var collapse = false, toc_visible = []; - - function init(config) { - // Instantiate search settings - _search = gitbook.storage.get("search", { - engine: config.search.engine || 'lunr', - opts: config.search.options || {}, - }); - }; - - // Save current search settings - function saveSearchSettings() { - gitbook.storage.set("search", _search); - } - - // Use a specific index - function loadIndex(data) { - // [Yihui] In bookdown, I use a character matrix to store the chapter - // content, and the index is dynamically built on the client side. - // Gitbook prebuilds the index data instead: https://github.com/GitbookIO/plugin-search - // We can certainly do that via R packages V8 and jsonlite, but let's - // see how slow it really is before improving it. 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Chapter 2 Overview of Metadata Types

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For each outcome type, include information on:

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    -
  • Overview of experimental procedures performed prior to collecting the data (and relevant technical parameters) -> refer to timeline diagram
    • -
  • Glossary of every variable in the tool: what precisely does it mean, what are the units, etc
    • -
  • Who collected the data (institution)
    • -
  • Replicates - were there any, are they different groups of islets, different individual cells, etc
    • -
  • Explanation of any changes in protocols (ie. switch to different GSIS concentrations, maybe different platform used halfway through, etc)
    • -
  • Whether data was intentionally collected on specific subsets of donors
    • -
  • Versions of data available for download
    • -
  • Data processing prior to statistical analysis (merging replicates, transformations, removed outliers, definition of any computed/normalized values)
    • -
  • Any additional notes
    • -
  • Citations of papers that have published parts of the data
    • -
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2.1 Donor Characteristics:

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Donor characteristics are provided to the Isletcore team through the organ procurement programs. These characteristics can come from the family and aren’t always accurate reflections of the medical history. Hba1c measurements are performed in the Isletcore when the donor blood sample is available.

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2.2 Organ Characteristics and Processing:

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Organ characteristic and processing data is recorded during the islet isolation by the lead technician. Cold Ischemia time will be calculated based on the cross clamp time during organ procurement until the start of the isolation in Edmonton.

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2.3 Isolation Outcomes:

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Islet purity, IEQ, % trapped, IPI are determined by the lead technician. Full details on determining IEQ, purity etc can be found here or in our IsletCore welcome booklet. Details on determining Insulin and DNA samples can always be found here. Cell proportion data is determined through our proteomics data. Proteomics samples are shipped to Jim Johnson’s lab at UBC. Samples are then hand picked and snap frozen for processing.

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2.4 Cell Culture Outcomes:

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On the day of shipping, Islets are recounted to determine IEQ, % recovery, IPI after culture. Culture time is determined by the end of the isolation until approximately 9am on a shipping day. Post culture samples are collected for insulin and DNA as previously described.

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2.5 Static Insulin Secretion:

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In triplicates, 15 hand picked islets from each donor were sequentially treated with low glucose for 1 hour followed by high glucose 1 hour. Collected supernatant for low glucose, high glucose or insulin content are measured by ELISA and recorded in the database. For each donor, there are multiple glucose combinations that may have been used. Glucose pairs are 1mM to 10mM glucose, 1mM to 16.7mM glucose or 2.8mM glucose to 16.7mM glucose. Islets used in the 1mM to 10mM group are unique from the 1mM to 16.7mM group. The secretion data are commonly presented as a percentage of the total content (secreted insulin/total insulin *100), and as a stimulation index (high glucose secretion/low glucose secretion). Biological outliers were defined as “Seth is coming up with the definition now”, and identified outliers were removed from the dataset. The data for each replicate (after outlier removal) can be downloaded from the data export page. The total insulin content, secretion percentages, and stimulation indices, averaged across replicates, can be queried, analyzed, and visualized in the other parts of the tool. Complete experimental details can be found here.

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2.6 Islet Oxygen Consumption (Seahorse assay):

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2.7 Dynamic Insulin Responses to Macronutrients:

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Human islets are shipped to Jim Johnson’s lab at UBC. Islets are hand picked and cultured in RPMI for 24-72hrs before the experiment to allow the islets to recover from shipping. 65 islets are loaded per chamber and pre-incubated for 1 hour. Islets are stimulated with 6 or 15mM glucose, 5mM Leucine or 0.75mM Oleic acid/0.75mM palmitic acid as indicated. Samples are stored at -20C until analysis with RIA. Full details are described here.

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2.8 Single-cell Function (electrophysiology)

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Human islets are hand picked and dispersed into single cells and plated on 35mm cell culture dishes by the MacDonald lab. 24-72 hours after the dispersion, electrophysiological measurements are recorded. Cell identity is confirmed by immunohistochemistry.

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Chapter 3 Overview of Omics Data Types

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For each data type, include information on:

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  • Platform(s)
    • -
  • Batches (and whether batch effect is significant)
    • -
  • Any logistical (shipping, storage)/lab procedures conducted prior to collecting data (and indicate relevant technical parameters - ie. culture times, etc)
    • -
  • Whether data was intentionally collected on specific subsets of donors
    • -
  • Raw data processing pipeline
    • -
  • Where you can find raw data files
    • -
  • Missing value strategy, filtering, and normalization prior to statistical analysis
    • -
  • Any additional notes
    • -
  • Citations of papers that have published parts of the data
    • -
-
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3.1 Gene expression (bulk RNA-seq)

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RNA-seq profiles were collected starting in [YEAR]in batches of islets from ~10-20 donors. [Include information on batches]. Raw reads were aligned to the [BLANK GENOME] using [BLANK SOFTWARE version BLANK]. The counts matrix was filtered to remove any genes with fewer than [X] mean counts. The counts were normalized for sequencing depth and adjusted to account for high variance/high abundant genes using the [BLANK] method in the limma voom R package (version #). Batch effect was corrected using the Combat-Seq R package (version #). Since

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3.2 Gene expression (Nanostring)

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50 islets are hand picked in Edmonton. Cells are washed with PBS then collected in 100ul of RLT Beta-mercaptoethanol. Islets arestored at -80C before shipping to the Lynn Lab.

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3.3 Protein expression (proteomics)

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Human islets are shipped to Jim Johnson’s lab at UBC. 300 Islets are hand picked, washed with pbs and pellet is snap frozen and stored at -80C. Details of lysis and analysis are found here.

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3.4 Gene expression (single-cell RNA-seq)

-
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3.5 Gene expression (pseudobulk RNA-seq)

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150 islets are hand picked at the University of Alberta and transferred into a tube with 1ml of Trizol reagent. Samples are stored at -80C until shipping to Anna Gloyn’s lab (originally Oxford now Stanford).

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Chapter 4 Overview of statistical analysis methods

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For each analysis, include details on:

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  • Specific methods (and R packages) used for each task (aimed for statisticians/data scientists)
    • -
  • Explanation of how the methods work, what they are useful for, and their limitations (aimed for biologists, not statisticians/data scientists)
    • -
  • Which parameters are exposed in the interface, what they do, and rationale for which parameters were exposed
    • -
  • How to interpret the results
    • -
  • How to report the results (which details/citations to include in methods sections of papers)
    • -
  • Any additional notes
    • -
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4.1 Multiple linear regression

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4.2 Spearman ranked correlation

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4.3 Overrepresentation analysis

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4.4 Gene set enrichment analysis

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4.5 Pipelines to generate significant feature associations for feature search page

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The data includes clinical metadata I envision a branching timeline, so that you can visualize everything that happened to an islet sample prior to the collection of each data type. Here is a rough outline of steps (I know it’s incomplete/wrong - will look at some of the guides on the IsletCore website to better sketch out) Pancreas procurement Shipping to Edmonton Islet isolation (more details here - I assume many/multiple steps) GSIS outcomes Other outcomes at UofA Shipping to other labs for seahorse, perifusion, omics Shipping to other labs (not in project) "],["overview-of-metadata-types.html", "Chapter 2 Overview of Metadata Types 2.1 Donor Characteristics: 2.2 Organ Characteristics and Processing: 2.3 Isolation Outcomes: 2.4 Cell Culture Outcomes: 2.5 Static Insulin Secretion: 2.6 Islet Oxygen Consumption (Seahorse assay): 2.7 Dynamic Insulin Responses to Macronutrients: 2.8 Single-cell Function (electrophysiology)", " Chapter 2 Overview of Metadata Types For each outcome type, include information on: Overview of experimental procedures performed prior to collecting the data (and relevant technical parameters) -> refer to timeline diagram Glossary of every variable in the tool: what precisely does it mean, what are the units, etc Who collected the data (institution) Replicates - were there any, are they different groups of islets, different individual cells, etc Explanation of any changes in protocols (ie. switch to different GSIS concentrations, maybe different platform used halfway through, etc) Whether data was intentionally collected on specific subsets of donors Versions of data available for download Data processing prior to statistical analysis (merging replicates, transformations, removed outliers, definition of any computed/normalized values) Any additional notes Citations of papers that have published parts of the data 2.1 Donor Characteristics: Donor characteristics are provided to the Isletcore team through the organ procurement programs. These characteristics can come from the family and aren’t always accurate reflections of the medical history. Hba1c measurements are performed in the Isletcore when the donor blood sample is available. 2.2 Organ Characteristics and Processing: Organ characteristic and processing data is recorded during the islet isolation by the lead technician. Cold Ischemia time will be calculated based on the cross clamp time during organ procurement until the start of the isolation in Edmonton. 2.3 Isolation Outcomes: Islet purity, IEQ, % trapped, IPI are determined by the lead technician. Full details on determining IEQ, purity etc can be found here or in our IsletCore welcome booklet. Details on determining Insulin and DNA samples can always be found here. Cell proportion data is determined through our proteomics data. Proteomics samples are shipped to Jim Johnson’s lab at UBC. Samples are then hand picked and snap frozen for processing. 2.4 Cell Culture Outcomes: On the day of shipping, Islets are recounted to determine IEQ, % recovery, IPI after culture. Culture time is determined by the end of the isolation until approximately 9am on a shipping day. Post culture samples are collected for insulin and DNA as previously described. 2.5 Static Insulin Secretion: In triplicates, 15 hand picked islets from each donor were sequentially treated with low glucose for 1 hour followed by high glucose 1 hour. Collected supernatant for low glucose, high glucose or insulin content are measured by ELISA and recorded in the database. For each donor, there are multiple glucose combinations that may have been used. Glucose pairs are 1mM to 10mM glucose, 1mM to 16.7mM glucose or 2.8mM glucose to 16.7mM glucose. Islets used in the 1mM to 10mM group are unique from the 1mM to 16.7mM group. The secretion data are commonly presented as a percentage of the total content (secreted insulin/total insulin *100), and as a stimulation index (high glucose secretion/low glucose secretion). Biological outliers were defined as “Seth is coming up with the definition now”, and identified outliers were removed from the dataset. The data for each replicate (after outlier removal) can be downloaded from the data export page. The total insulin content, secretion percentages, and stimulation indices, averaged across replicates, can be queried, analyzed, and visualized in the other parts of the tool. Complete experimental details can be found here. 2.6 Islet Oxygen Consumption (Seahorse assay): 2.7 Dynamic Insulin Responses to Macronutrients: Human islets are shipped to Jim Johnson’s lab at UBC. Islets are hand picked and cultured in RPMI for 24-72hrs before the experiment to allow the islets to recover from shipping. 65 islets are loaded per chamber and pre-incubated for 1 hour. Islets are stimulated with 6 or 15mM glucose, 5mM Leucine or 0.75mM Oleic acid/0.75mM palmitic acid as indicated. Samples are stored at -20C until analysis with RIA. Full details are described here. 2.8 Single-cell Function (electrophysiology) Human islets are hand picked and dispersed into single cells and plated on 35mm cell culture dishes by the MacDonald lab. 24-72 hours after the dispersion, electrophysiological measurements are recorded. Cell identity is confirmed by immunohistochemistry. "],["overview-of-omics-data-types.html", "Chapter 3 Overview of Omics Data Types 3.1 Gene expression (bulk RNA-seq) 3.2 Gene expression (Nanostring) 3.3 Protein expression (proteomics) 3.4 Gene expression (single-cell RNA-seq) 3.5 Gene expression (pseudobulk RNA-seq)", " Chapter 3 Overview of Omics Data Types For each data type, include information on: Platform(s) Batches (and whether batch effect is significant) Any logistical (shipping, storage)/lab procedures conducted prior to collecting data (and indicate relevant technical parameters - ie. culture times, etc) Whether data was intentionally collected on specific subsets of donors Raw data processing pipeline Where you can find raw data files Missing value strategy, filtering, and normalization prior to statistical analysis Any additional notes Citations of papers that have published parts of the data 3.1 Gene expression (bulk RNA-seq) RNA-seq profiles were collected starting in [YEAR]in batches of islets from ~10-20 donors. [Include information on batches]. Raw reads were aligned to the [BLANK GENOME] using [BLANK SOFTWARE version BLANK]. The counts matrix was filtered to remove any genes with fewer than [X] mean counts. The counts were normalized for sequencing depth and adjusted to account for high variance/high abundant genes using the [BLANK] method in the limma voom R package (version #). Batch effect was corrected using the Combat-Seq R package (version #). Since 3.2 Gene expression (Nanostring) 50 islets are hand picked in Edmonton. Cells are washed with PBS then collected in 100ul of RLT Beta-mercaptoethanol. Islets arestored at -80C before shipping to the Lynn Lab. 3.3 Protein expression (proteomics) Human islets are shipped to Jim Johnson’s lab at UBC. 300 Islets are hand picked, washed with pbs and pellet is snap frozen and stored at -80C. Details of lysis and analysis are found here. 3.4 Gene expression (single-cell RNA-seq) 3.5 Gene expression (pseudobulk RNA-seq) 150 islets are hand picked at the University of Alberta and transferred into a tube with 1ml of Trizol reagent. Samples are stored at -80C until shipping to Anna Gloyn’s lab (originally Oxford now Stanford). 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You may want to try searching to find the page's new location, or use the table of contents to find the page you are looking for. "]] diff --git a/docs/_book/style.css b/docs/_book/style.css deleted file mode 100644 index f317b43..0000000 --- a/docs/_book/style.css +++ /dev/null @@ -1,14 +0,0 @@ -p.caption { - color: #777; - margin-top: 10px; -} -p code { - white-space: inherit; -} -pre { - word-break: normal; - word-wrap: normal; -} -pre code { - white-space: inherit; -} diff --git a/docs/_bookdown.yml b/docs/_bookdown.yml deleted file mode 100644 index 30bf605..0000000 --- a/docs/_bookdown.yml +++ /dev/null @@ -1,4 +0,0 @@ -delete_merged_file: true -language: - ui: - chapter_name: "Chapter " diff --git a/docs/_output.yml b/docs/_output.yml deleted file mode 100644 index 58bb0e0..0000000 --- a/docs/_output.yml +++ /dev/null @@ -1,19 +0,0 @@ -bookdown::gitbook: - css: style.css - config: - toc: - before: | -
  • Human Islets
    • - - edit: https://github.com/yao-lzy/HumanIslets/edit/main/example/%s - download: ["pdf", "epub"] - search: - enabled: true - content_selector: '.markdown-body' -bookdown::pdf_book: - includes: - in_header: preamble.tex - latex_engine: xelatex - citation_package: natbib - keep_tex: yes -bookdown::epub_book: default diff --git a/docs/book.bib b/docs/book.bib deleted file mode 100644 index f275a09..0000000 --- a/docs/book.bib +++ /dev/null @@ -1,10 +0,0 @@ -@Book{xie2015, - title = {Dynamic Documents with {R} and knitr}, - author = {Yihui Xie}, - publisher = {Chapman and Hall/CRC}, - address = {Boca Raton, Florida}, - year = {2015}, - edition = {2nd}, - note = {ISBN 978-1498716963}, - url = {http://yihui.org/knitr/}, -} diff --git a/docs/index.Rmd b/docs/index.Rmd deleted file mode 100644 index 51de750..0000000 --- a/docs/index.Rmd +++ /dev/null @@ -1,26 +0,0 @@ ---- -title: "Human Islets" -author: "" -date: "`r Sys.Date()`" -site: bookdown::bookdown_site -output: bookdown::gitbook -documentclass: book - -description: | - This is an introduction of the Human Islet project. ---- - -# General Introduction - -The HumanIslets tool houses data collected from or associated with human islets procured by the University of Alberta. The data includes clinical metadata - -I envision a branching timeline, so that you can visualize everything that happened to an islet sample prior to the collection of each data type. Here is a rough outline of steps (I know it’s incomplete/wrong - will look at some of the guides on the IsletCore website to better sketch out) - - 1. Pancreas procurement - 2. Shipping to Edmonton - 3. Islet isolation (more details here - I assume many/multiple steps) - 4. GSIS outcomes - 5. Other outcomes at UofA - 6. Shipping to other labs for seahorse, perifusion, omics - 7. Shipping to other labs (not in project) - diff --git a/docs/preamble.tex b/docs/preamble.tex deleted file mode 100644 index dfd2e14..0000000 --- a/docs/preamble.tex +++ /dev/null @@ -1 +0,0 @@ -\usepackage{booktabs} diff --git a/docs/style.css b/docs/style.css deleted file mode 100644 index f317b43..0000000 --- a/docs/style.css +++ /dev/null @@ -1,14 +0,0 @@ -p.caption { - color: #777; - margin-top: 10px; -} -p code { - white-space: inherit; -} -pre { - word-break: normal; - word-wrap: normal; -} -pre code { - white-space: inherit; -}