1. crisprScore
  2. Commit 6f2475d61a0623b7dd82df77d6bfbbf88c5c6daf
Browse code

Updated doc, and added crisprRater

fortinj2 authored on 24/06/2022 19:08:17
Showing 11 changed files
DESCRIPTION
History View file @ 6f2475d
... ... 
@@ -1,5 +1,5 @@
1 1 
 Package: crisprScore
2 
-Version: 1.1.2
2 
+Version: 1.1.3
3 3 
 Date: 2022-06-22
4 4 
 Title: On-Target and Off-Target Scoring Algorithms for CRISPR gRNAs
5 5 
 Authors@R: c(
NAMESPACE
History View file @ 6f2475d
... ... 
@@ -2,6 +2,7 @@
2 2
3 3 
 export(getAzimuthScores)
4 4 
 export(getCFDScores)
5 
+export(getCRISPRaterScores)
5 6 
 export(getCRISPRscanScores)
6 7 
 export(getCasRxRFScores)
7 8 
 export(getCrispraiScores)
R/getCrispraterScores.R
History View file @ 6f2475d
... ... 
@@ -1,33 +1,76 @@
1 
+#' @title Calculate on-target sgRNA activity scores for Cas9 using CRISPRater
2 
+#' @description Calculate on-target sgRNA activity scores for
3 
+#'     CRISPR/Cas9-induced knockout using the DeepHF scoring method. Both U6
4 
+#'     and T7 promoters are supported. Three different versions of the SpCas9
5 
+#'     nuclease are supported: wildtype (WT-SpCas9), high-fidelity Cas9
6 
+#'     (SpCas9-HF1) and enhanced Cas9 (eSpCas9). Currently not supported
7 
+#'     on Windows machines.
8 
+#'
9 
+#' @param sequences Character vector of 20bp protospacer sequences.
10 
+#'
11 
+#' @details Input sequences for CRISPRater scoring must be 20 spacer sequences.
12 
+#'
13 
+#' @return \strong{getCrisprRaterScores} returns a data.frame with
14 
+#'     \code{sequence} and \code{score} columns. The CRISPRater score takes on
15 
+#'     a value between 0 and 1. A higher score indicates higher knockout
16 
+#'     efficiency.
17 
+#'
18 
+#'
19 
+#' @references
20 
+#' Labuhn M, Adams FF, Ng M, et al. Refined sgRNA efficacy prediction improves
21 
+#' large-and small-scale CRISPR–Cas9 applications. Nucleic acids research. 2018
22 
+#' Feb 16;46(3):1375-85.
23 
+#'
24 
+#' @author Jean-Philippe Fortin
25 
+#'
26 
+#' @examples
27 
+#' spacer  <- "ATCGATGCTGATGCTAGATA" #20bp
28 
+#' results <- getCRISPRaterScores(spacer)
29 
+#'
30 
+#' @export
31 
+getCRISPRaterScores <- function(sequences){
32 
+
33 
+    sequences <- .checkSequenceInputs(sequences)
34 
+    if (unique(nchar(sequences))!=20){
35 
+        stop("Provided sequences must have length 20nt (20nt-spacer")
36 
+    }
37 
+    results <- .getModelScoreCRISPRater(sequences)
38 
+    return(results)
39 
+}
40 
+
1 41
2 42
3 43 
 # Must be 20nt long
4 44 
 #spacers <- c("GGTGCTGATGCTGTGTGATG",
5 45 
 #             "GGTGCTGATAAAGTGTGATG")
6 
-.getModelScore <- function(spacers){
7 
-    features <- .extractFeatures(spacers)
8 
-    score <- model_offset + model_weights%*%t(features)
46 
+.getModelScoreCRISPRater <- function(sequences){
47 
+
48 
+    model_weights <- c(0.14177385,
49 
+                       0.06966514,
50 
+                       0.04216254,
51 
+                       0.03303432,
52 
+                       0.02355430,
53 
+                       -0.04746424,
54 
+                       -0.04878001,
55 
+                       -0.06981921,
56 
+                       -0.07087756,
57 
+                       -0.08160700)
58 
+    model_offset <- 0.6505037
59 
+
60 
+    features <- .extractFeaturesForCRISPRater(sequences)
61 
+    score <- model_offset + model_weights %*% t(features)
9 62 
     return(score)
10 63 
 }
11 64
12 
-model_weights <- c(0.14177385,
13 
-                   0.06966514,
14 
-                   0.04216254,
15 
-                   0.03303432,
16 
-                   0.02355430,
17 
-                   -0.04746424,
18 
-                   -0.04878001,
19 
-                   -0.06981921,
20 
-                   -0.07087756,
21 
-                   -0.08160700)
22 
-model_offset <- 0.6505037
65 
+
23 66
24 67
25 68 
 #' @importFrom Biostrings DNAStringSet letterFrequency
26 
-.extractFeatures <- function(spacers){
27 
-    gc <- rowSums(letterFrequency(DNAStringSet(substr(spacers,4,14)),
69 
+.extractFeaturesForCRISPRater <- function(sequences){
70 
+    gc <- rowSums(letterFrequency(DNAStringSet(substr(sequences,4,14)),
28 71 
                                   c("G", "C")))/10
29 
-    spacers <- DNAStringSet(spacers)
30 
-    mat <- as.matrix(DNAStringSet(spacers))
72 
+    sequences <- DNAStringSet(sequences)
73 
+    mat <- as.matrix(DNAStringSet(sequences))
31 74 
     features <- list()
32 75 
     features[[1]] <- gc
33 76 
     features[[2]] <- mat[,20,drop=FALSE]=="G"
data/scoringMethodsInfo.rda
History View file @ 6f2475d
34 77 
Binary files a/data/scoringMethodsInfo.rda and b/data/scoringMethodsInfo.rda differ
inst/roster/methods.txt
History View file @ 6f2475d
... ... 
@@ -9,4 +9,5 @@ deepcpf1	AsCas12a	-4	29	On-target	DeepCpf1
9 9 
 enpamgb	enAsCas12a	-4	29	On-target	EnPAMGB
10 10 
 crisprscan	SpCas9	-26	8	On-target	CRISPRscan
11 11 
 casrxrf	CasRx	NA	NA	On-target	CasRx-RF
12 
-crisprai	SpCas9	-19	2	On-target	CRISPRai
13 12 
\ No newline at end of file
13 
+crisprai	SpCas9	-19	2	On-target	CRISPRai
14 
+crisprater	SpCas9	-20	-1	On-target	CRISPRater
14 15 
\ No newline at end of file
man/getCRISPRaterScores.Rd
History View file @ 6f2475d
15 16 
new file mode 100644
... ... 
@@ -0,0 +1,41 @@
1 
+% Generated by roxygen2: do not edit by hand
2 
+% Please edit documentation in R/getCRISPRaterScores.R
3 
+\name{getCRISPRaterScores}
4 
+\alias{getCRISPRaterScores}
5 
+\title{Calculate on-target sgRNA activity scores for Cas9 using CRISPRater}
6 
+\usage{
7 
+getCRISPRaterScores(sequences)
8 
+}
9 
+\arguments{
10 
+\item{sequences}{Character vector of 20bp protospacer sequences.}
11 
+}
12 
+\value{
13 
+\strong{getCrisprRaterScores} returns a data.frame with
14 
+    \code{sequence} and \code{score} columns. The CRISPRater score takes on
15 
+    a value between 0 and 1. A higher score indicates higher knockout
16 
+    efficiency.
17 
+}
18 
+\description{
19 
+Calculate on-target sgRNA activity scores for
20 
+    CRISPR/Cas9-induced knockout using the DeepHF scoring method. Both U6
21 
+    and T7 promoters are supported. Three different versions of the SpCas9
22 
+    nuclease are supported: wildtype (WT-SpCas9), high-fidelity Cas9
23 
+    (SpCas9-HF1) and enhanced Cas9 (eSpCas9). Currently not supported
24 
+    on Windows machines.
25 
+}
26 
+\details{
27 
+Input sequences for CRISPRater scoring must be 20 spacer sequences.
28 
+}
29 
+\examples{
30 
+spacer  <- "ATCGATGCTGATGCTAGATA" #20bp
31 
+results <- getCRISPRaterScores(spacer)
32 
+
33 
+}
34 
+\references{
35 
+Labuhn M, Adams FF, Ng M, et al. Refined sgRNA efficacy prediction improves
36 
+large-and small-scale CRISPR–Cas9 applications. Nucleic acids research. 2018
37 
+Feb 16;46(3):1375-85.
38 
+}
39 
+\author{
40 
+Jean-Philippe Fortin
41 
+}
vignettes/crisprScore.Rmd
History View file @ 6f2475d
... ... 
@@ -2,13 +2,13 @@
2 2 
 title: "On-target and off-target scoring for CRISPR/Cas systems"
3 3 
 author:
4 4 
 - name: Jean-Philippe Fortin
5 
-  affiliation: OMNI Bioinformatics, gRED, Genentech
5 
+  affiliation: Data Science and Statistical Computing, gRED, Genentech
6 6 
   email: [email protected]
7 7 
 - name: Aaron Lun
8 
-  affiliation: Data Science Statistical Computing, gRED, Genentech
8 
+  affiliation: Data Science and Statistical Computing, gRED, Genentech
9 9 
   email: [email protected]
10 10 
 - name: Luke Hoberecht
11 
-  affiliation: OMNI Bioinformatics, gRED, Genentech
11 
+  affiliation: Data Science and Statistical Computing, gRED, Genentech
12 12 
   email: [email protected]
13 13 
 date: "`r Sys.Date()`"
14 14 
 output:
... ... 
@@ -59,11 +59,16 @@ file in order for `crisprScore` to work properly:
59 59 
 options(reticulate.useImportHook=FALSE)
60 60 
 ```
61 61
62 
+We load `crisprScore` in the usual way:
63 
+
64 
+```{r, warnings=FALSE, message=FALSE}
65 
+library(crisprScore)
66 
+```
67 
+
62 68 
 The `scoringMethodsInfo` data.frame contains a succinct summary of scoring
63 69 
 methods available in `crisprScore`:
64 70
65 71 
 ```{r}
66 
-library(crisprScore)
67 72 
 data(scoringMethodsInfo)
68 73 
 print(scoringMethodsInfo)
69 74 
 ```
... ... 
@@ -74,21 +79,21 @@ See `?scoringMethodsInfo` for more information about the different columns.
74 79
75 80 
 Predicting on-target cutting efficiency is an extensive area of research, and
76 81 
 we try to provide in `crisprScore` the latest state-of-the-art algorithms as
77 
-they become available. Different algorithms require different input nucleotide
78 
-sequences to predict cutting efficiency as illustrated in the two
79 
-figures below.
82 
+they become available.
83 
+
84 
+## Cas9 methods
80 85
86 
+Different algorithms require different input nucleotide
87 
+sequences to predict cutting efficiency as illustrated in the figure below.
81 88
82 89 
 ```{r, echo=FALSE,fig.cap="Sequence inputs for Cas9 scoring methods"}
83 90 
 knitr::include_graphics("./figures/sequences_cas9.svg")
84 91 
 ```
85 92
86 
-```{r, echo=FALSE, fig.cap="Sequence inputs for Cas12a scoring methods"}
87 
-knitr::include_graphics("./figures/sequences_cas12a.svg")
88 
-```
89 93
90 94
91 
-## Rule Set 1 (Cas9)
95 
+
96 
+### Rule Set 1 (SpCas9)
92 97
93 98 
 The Rule Set 1 algorithm is one of the first on-target efficiency methods
94 99 
 developed for the Cas9 nuclease [@ruleset1]. It generates a probability
... ... 
@@ -108,7 +113,7 @@ results <- getRuleSet1Scores(input)
108 113 
 The Azimuth score described below is an improvement over Rule Set 1
109 114 
 from the same lab.
110 115
111 
-## Azimuth score (Cas9)
116 
+### Azimuth score (SpCas9)
112 117
113 118 
 The Azimuth algorithm is an improved version of the popular Rule Set 2 score for
114 119 
 the Cas9 nuclease [@azimuth]. It generates a probability (therefore a score
... ... 
@@ -125,7 +130,7 @@ input  <- paste0(flank5, spacer, pam, flank3)
125 130 
 results <- getAzimuthScores(input)
126 131 
 ```
127 132
128 
-## DeepHF score (Cas9)
133 
+### DeepHF score (SpCas9, HF-SpCas9)
129 134
130 135 
 The DeepHF algorithm is an on-target cutting efficiency prediction algorithm for
131 136 
 several variants of the Cas9 nuclease [@deepcas9] using a recurrent neural
... ... 
@@ -148,7 +153,95 @@ also specify the promoter used for expressing sgRNAs using the argument
148 153 
 `promoter` ("U6" by default). See `?getDeepHFScores` for more details.
149 154
150 155
151 
-## DeepCpf1 score (Cas12a)
156 
+
157 
+
158 
+
159 
+
160 
+
161 
+
162 
+### CRISPRscan (Moreno-Mateos score, SpCas9)
163 
+
164 
+The CRISPRscan algorithm, also known as the Moreno-Mateos score), is an
165 
+on-target efficiency method for the SpCas9 nuclease developed for sgRNAs
166 
+expressed from a T7 promoter, and trained on zebrafish data [@crisprscan].
167 
+It generates a probability (therefore a score between 0 and 1) that a given
168 
+sgRNA will cut at its intended target.
169 
+6 nucleotides upstream of the protospacer sequence
170 
+and 6 nucleotides downstream of the PAM sequence are needed for scoring:
171 
+
172 
+```{r, eval=TRUE}
173 
+flank5 <- "ACCTAA" #6bp
174 
+spacer <- "ATCGATGCTGATGCTAGATA" #20bp
175 
+pam    <- "AGG" #3bp
176 
+flank3 <- "TTGAAT" #6bp
177 
+input  <- paste0(flank5, spacer, pam, flank3)
178 
+results <- getCRISPRscanScores(input)
179 
+```
180 
+
181 
+
182 
+
183 
+### CRISPRater (SpCas9)
184 
+
185 
+The CRISPRater algorithm is an on-target efficiency method for the SpCas9 nuclease [@crisprater].
186 
+It generates a probability (therefore a score between 0 and 1) that a given
187 
+sgRNA will cut at its intended target.
188 
+Only the 20bp spacer sequence is required.
189 
+
190 
+```{r, eval=TRUE}
191 
+spacer <- "ATCGATGCTGATGCTAGATA" #20bp
192 
+results <- getCRISPRaterScores(spacer)
193 
+```
194 
+
195 
+### CRISPRai (SpCas9)
196 
+
197 
+The CRISPRai algorithm was developed by the Weissman lab to score SpCas9 gRNAs for CRISPRa and CRISPRi applications [@crisprai], for the human genome. The function `getCrispraiScores` requires several inputs.
198 
+
199 
+First, it requires a data.frame specifying the genomic coordinates of the transcription starting sites (TSSs).
200 
+An example of such a data.frame is provided in the crisprScore package:
201 
+
202 
+```{r, eval=TRUE}
203 
+head(tssExampleCrispri)
204 
+```
205 
+
206 
+It also requires a data.frame specifying the genomic coordinates of the  gRNA sequences to score. An example of such a data.frame is provided in the crisprScore package:
207 
+
208 
+```{r, eval=TRUE}
209 
+head(sgrnaExampleCrispri)
210 
+```
211 
+
212 
+All columns  present in `tssExampleCrispri` and `sgrnaExampleCrispri` are mandatory for `getCrispraiScores` to work.
213 
+
214 
+Two additional arguments are required: `fastaFile`, to specify the path of the fasta file of the human reference genome, and `chromatinFiles`, which is a list specifying the path of files containing chromatin accessibility genomic tracks in hg38 coordinates. The chromatin files can be downloaded from Zenodo at the following link:  [Currently being uploaded].
215 
+The fasta file for the human genome (hg38) can be dowloaded directly from here:
216 
+https://hgdownload.soe.ucsc.edu/goldenPath/hg38/bigZips/hg38.fa.gz
217 
+
218 
+
219 
+
220 
+One can obtain the CRISPRai scores using the following command:
221 
+
222 
+```{r, eval=FALSE}
223 
+results <- getCrispraiScores(tss_df=tssExampleCrispri,
224 
+                             sgrna_df=sgrnaExampleCrispri,
225 
+                             modality="CRISPRi",
226 
+                             fastaFile="your/path/hg38.fa",
227 
+                             chromatinFiles=list(mnase="path/to/mnaseFile.bw",
228 
+                                                 dnase="path/to/dnaseFile.bw",
229 
+                                                 faire="oath/to/faireFile.bw"))
230 
+```
231 
+
232 
+The function works identically for CRISPRa applications, with modality replaced
233 
+by `CRISPRa`.
234 
+
235 
+## Cas12a methods
236 
+
237 
+Different algorithms require different input nucleotide
238 
+sequences to predict cutting efficiency as illustrated in the figure below.
239 
+
240 
+```{r, echo=FALSE, fig.cap="Sequence inputs for Cas12a scoring methods"}
241 
+knitr::include_graphics("./figures/sequences_cas12a.svg")
242 
+```
243 
+
244 
+### DeepCpf1 score (AsCas12a)
152 245
153 246 
 The DeepCpf1 algorithm is an on-target cutting efficiency prediction algorithm
154 247 
 for the Cas12a nuclease [@deepcpf1] using a convolutional neural network (CNN)
... ... 
@@ -166,10 +259,7 @@ input  <- paste0(flank5, pam, spacer, flank3)
166 259 
 results <- getDeepCpf1Scores(input)
167 260 
 ```
168 261
169 
-
170 
-
171 
-
172 
-## enPAM+GB score (enCas12a)
262 
+### enPAM+GB score (enCas12a)
173 263
174 264 
 The enPAM+GB algorithm is an on-target cutting efficiency prediction algorithm
175 265 
 for the enhanced Cas12a (enCas12a) nuclease [@enpamgb] using a gradient-booster
... ... 
@@ -189,23 +279,25 @@ input  <- paste0(flank5, pam, spacer, flank3)
189 279 
 results <- getEnPAMGBScores(input)
190 280 
 ```
191 281
192 
-## CRISPRscan (Moreno-Mateos score)
193 282
194 
-The CRISPRscan algorithm, also known as the Moreno-Mateos score), is an
195 
-on-target efficiency method for the SpCas9 nuclease developed for sgRNAs
196 
-expressed from a T7 promoter, and trained on zebrafish data [@crisprscan].
197 
-It generates a probability (therefore a score between 0 and 1) that a given
198 
-sgRNA will cut at its intended target.
199 
-6 nucleotides upstream of the protospacer sequence
200 
-and 6 nucleotides downstream of the PAM sequence are needed for scoring:
283 
+## Cas13d methods
201 284
202 
-```{r, eval=TRUE}
203 
-flank5 <- "ACCTAA" #6bp
204 
-spacer <- "ATCGATGCTGATGCTAGATA" #20bp
205 
-pam    <- "AGG" #3bp
206 
-flank3 <- "TTGAAT" #6bp
207 
-input  <- paste0(flank5, spacer, pam, flank3)
208 
-results <- getCRISPRscanScores(input)
285 
+### CasRxRF (RfxCas13d)
286 
+
287 
+The CasRxRF method was developed to characterize on-target efficiency of the RNA-targeting nuclease RfxCas13d, abbreviated as CasRx [@casrxrf].
288 
+
289 
+It requires as an input the mRNA sequence targeted by the gRNAs, and returns as an output on-target efficiency scores for all gRNAs targeting the mRNA sequence.
290 
+
291 
+As an example, we predict on-target efficiency for gRNAs targeting the mRNA sequence stored in the file `test.fa`:
292 
+
293 
+
294 
+```{r, eval=FALSE}
295 
+fasta <- file.path(system.file(package="crisprScore"),
296 
+                   "casrxrf/test.fa")
297 
+mrnaSequence <- Biostrings::readDNAStringSet(filepath=fasta
298 
+                                             format="fasta",
299 
+                                             use.names=TRUE)
300 
+results <- getCasRxRFScores(mrnaSequence)
209 301 
 ```
210 302
211 303
vignettes/figures/sequences_cas9.pdf
History View file @ 6f2475d
212 304 
Binary files a/vignettes/figures/sequences_cas9.pdf and b/vignettes/figures/sequences_cas9.pdf differ
vignettes/figures/sequences_cas9.pptx
History View file @ 6f2475d
213 305 
Binary files a/vignettes/figures/sequences_cas9.pptx and b/vignettes/figures/sequences_cas9.pptx differ
vignettes/figures/sequences_cas9.svg
History View file @ 6f2475d
... ... 
@@ -6,575 +6,691 @@
6 6 
    id="svg2"
7 7 
    xml:space="preserve"
8 8 
    width="1296"
9 
-   height="480"
10 
-   viewBox="0 0 1296 480"
9 
+   height="498.66666"
10 
+   viewBox="0 0 1296 498.66666"
11 11 
    xmlns="http://www.w3.org/2000/svg"
12 12 
    xmlns:svg="http://www.w3.org/2000/svg"><defs
13 13 
      id="defs6"><clipPath
14 14 
        clipPathUnits="userSpaceOnUse"
15 15 
        id="clipPath18"><path
16 
-         d="M 0,8.046627e-6 H 971.76 V 360.00001 H 0 Z"
16 
+         d="M 0,0.08000836 H 971.76 V 374.00001 H 0 Z"
17 17 
          id="path16" /></clipPath></defs><g
18 18 
      id="g8"
19 
-     transform="matrix(1.3333333,0,0,-1.3333333,0,480)"><g
19 
+     transform="matrix(1.3333333,0,0,-1.3333333,0,498.66667)"><g
20 20 
        id="g10" /><g
21 21 
        id="g12"><g
22 22 
          id="g14"
23 23 
          clip-path="url(#clipPath18)"><path
24 
-           d="M 0,360 H 971.76 V 8.046627e-6 H 0 Z"
24 
+           d="M 0,374 H 971.76 V 0.08000836 H 0 Z"
25 25 
            style="fill:#ffffff;fill-opacity:1;fill-rule:nonzero;stroke:none"
26 26 
            id="path20" /></g></g><g
27 27 
        id="g22"><path
28 
-         d="M 0,360 H 972 V 9.387731e-6 H 0 Z"
28 
+         d="M 0,374 H 972 V -0.3750296 H 0 Z"
29 29 
          style="fill:#ffffff;fill-opacity:1;fill-rule:nonzero;stroke:none"
30 30 
          id="path24" /><g
31 31 
          id="g26"
32 
-         transform="matrix(0.24,0,0,0.24,355.1134,-126)"><text
33 
-           transform="matrix(1,0,0,-1,0,1500)"
32 
+         transform="matrix(0.24,0,0,0.24,355.1134,-177.28)"><text
33 
+           transform="matrix(1,0,0,-1,0,1558)"
34 34 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
35 35 
            id="text30"><tspan
36 36 
              x="0 62.500019 125.00004 187.50006 250.00008 312.50009 375.00012 437.50015 500.00015 562.50018 625.00018 687.50024 750.00024 812.50024 875.00031 937.50031"
37 37 
              y="0"
38 38 
              id="tspan28">ATCGATGCTGATGCTA</tspan></text></g><g
39 39 
          id="g32"
40 
-         transform="matrix(0.24,0,0,0.24,595.1134,-126)"><text
41 
-           transform="matrix(1,0,0,-1,0,1500)"
40 
+         transform="matrix(0.24,0,0,0.24,595.1134,-177.28)"><text
41 
+           transform="matrix(1,0,0,-1,0,1558)"
42 42 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
43 43 
            id="text36"><tspan
44 44 
              x="0"
45 45 
              y="0"
46 46 
              id="tspan34">G</tspan></text></g><g
47 47 
          id="g38"
48 
-         transform="matrix(0.24,0,0,0.24,610.1134,-126)"><text
49 
-           transform="matrix(1,0,0,-1,0,1500)"
48 
+         transform="matrix(0.24,0,0,0.24,610.1134,-177.28)"><text
49 
+           transform="matrix(1,0,0,-1,0,1558)"
50 50 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
51 51 
            id="text42"><tspan
52 52 
              x="0 62.500019 125.00004"
53 53 
              y="0"
54 54 
              id="tspan40">ATA</tspan></text></g><g
55 55 
          id="g44"
56 
-         transform="matrix(0.24,0,0,0.24,655.1134,-126)"><text
57 
-           transform="matrix(1,0,0,-1,0,1500)"
56 
+         transform="matrix(0.24,0,0,0.24,655.1134,-177.28)"><text
57 
+           transform="matrix(1,0,0,-1,0,1558)"
58 58 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
59 59 
            id="text48"><tspan
60 60 
              x="0"
61 61 
              y="0"
62 62 
              id="tspan46">A</tspan></text></g><g
63 63 
          id="g50"
64 
-         transform="matrix(0.24,0,0,0.24,670.1134,-126)"><text
65 
-           transform="matrix(1,0,0,-1,0,1500)"
64 
+         transform="matrix(0.24,0,0,0.24,670.1134,-177.28)"><text
65 
+           transform="matrix(1,0,0,-1,0,1558)"
66 66 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#c55a11;fill-opacity:1;fill-rule:nonzero;stroke:none"
67 67 
            id="text54"><tspan
68 68 
              x="0 62.500019"
69 69 
              y="0"
70 70 
              id="tspan52">GG</tspan></text></g><g
71 71 
          id="g56"
72 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.421,240.6492)"><path
72 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.4213,203.41)"><path
73 73 
            d="M 0,0 2785439,1"
74 74 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
75 75 
            id="path58" /></g><g
76 76 
          id="g60"
77 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.4206,207.5347)"><path
77 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.4206,173.3378)"><path
78 78 
            d="M 0,0 2054114,1"
79 79 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
80 80 
            id="path62" /></g><g
81 81 
          id="g64"
82 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,709.5364,240.6492)"><path
82 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,709.5367,203.41)"><path
83 83 
            d="M 0,0 2573401,1"
84 84 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
85 85 
            id="path66" /></g><g
86 86 
          id="g68"
87 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,755.3,207.5347)"><path
87 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,755.3003,173.3378)"><path
88 88 
            d="M 0,0 1992203,1"
89 89 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
90 90 
            id="path70" /></g><g
91 91 
          id="g72"
92 
-         transform="matrix(0.24,0,0,0.24,50.45334,-123.36)"><text
93 
-           transform="matrix(1,0,0,-1,0,1500)"
92 
+         transform="matrix(0.24,0,0,0.24,50.45397,-174.64)"><text
93 
+           transform="matrix(1,0,0,-1,0,1558)"
94 94 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
95 95 
            id="text76"><tspan
96 96 
              x="0 46.357498 83.864998 121.3725 160.98 207.8625"
97 97 
              y="0"
98 98 
              id="tspan74">DeepHF</tspan></text></g><g
99 99 
          id="g78"
100 
-         transform="matrix(0.24,0,0,0.24,295.3618,-159.6)"><text
101 
-           transform="matrix(1,0,0,-1,0,1500)"
100 
+         transform="matrix(0.24,0,0,0.24,295.3618,-207.76)"><text
101 
+           transform="matrix(1,0,0,-1,0,1558)"
102 102 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#a9d18e;fill-opacity:1;fill-rule:nonzero;stroke:none"
103 103 
            id="text82"><tspan
104 104 
              x="0 62.500019 125.00004 187.50006"
105 105 
              y="0"
106 106 
              id="tspan80">ACCT</tspan></text></g><g
107 107 
          id="g84"
108 
-         transform="matrix(0.24,0,0,0.24,355.3618,-159.6)"><text
109 
-           transform="matrix(1,0,0,-1,0,1500)"
108 
+         transform="matrix(0.24,0,0,0.24,355.3618,-207.76)"><text
109 
+           transform="matrix(1,0,0,-1,0,1558)"
110 110 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
111 111 
            id="text88"><tspan
112 112 
              x="0 62.500019 125.00004 187.50006 250.00008 312.50009 375.00012 437.50015 500.00015 562.50018 625.00018 687.50024 750.00024 812.50024 875.00031 937.50031"
113 113 
              y="0"
114 114 
              id="tspan86">ATCGATGCTGATGCTA</tspan></text></g><g
115 115 
          id="g90"
116 
-         transform="matrix(0.24,0,0,0.24,595.3618,-159.6)"><text
117 
-           transform="matrix(1,0,0,-1,0,1500)"
116 
+         transform="matrix(0.24,0,0,0.24,595.3618,-207.76)"><text
117 
+           transform="matrix(1,0,0,-1,0,1558)"
118 118 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
119 119 
            id="text94"><tspan
120 120 
              x="0"
121 121 
              y="0"
122 122 
              id="tspan92">G</tspan></text></g><g
123 123 
          id="g96"
124 
-         transform="matrix(0.24,0,0,0.24,610.3618,-159.6)"><text
125 
-           transform="matrix(1,0,0,-1,0,1500)"
124 
+         transform="matrix(0.24,0,0,0.24,610.3618,-207.76)"><text
125 
+           transform="matrix(1,0,0,-1,0,1558)"
126 126 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
127 127 
            id="text100"><tspan
128 128 
              x="0 62.500019 125.00004"
129 129 
              y="0"
130 130 
              id="tspan98">ATA</tspan></text></g><g
131 131 
          id="g102"
132 
-         transform="matrix(0.24,0,0,0.24,655.3618,-159.6)"><text
133 
-           transform="matrix(1,0,0,-1,0,1500)"
132 
+         transform="matrix(0.24,0,0,0.24,655.3618,-207.76)"><text
133 
+           transform="matrix(1,0,0,-1,0,1558)"
134 134 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
135 135 
            id="text106"><tspan
136 136 
              x="0"
137 137 
              y="0"
138 138 
              id="tspan104">A</tspan></text></g><g
139 139 
          id="g108"
140 
-         transform="matrix(0.24,0,0,0.24,670.3618,-159.6)"><text
141 
-           transform="matrix(1,0,0,-1,0,1500)"
140 
+         transform="matrix(0.24,0,0,0.24,670.3618,-207.76)"><text
141 
+           transform="matrix(1,0,0,-1,0,1558)"
142 142 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#c55a11;fill-opacity:1;fill-rule:nonzero;stroke:none"
143 143 
            id="text112"><tspan
144 144 
              x="0 62.500019"
145 145 
              y="0"
146 146 
              id="tspan110">GG</tspan></text></g><g
147 147 
          id="g114"
148 
-         transform="matrix(0.24,0,0,0.24,700.3618,-159.6)"><text
149 
-           transform="matrix(1,0,0,-1,0,1500)"
148 
+         transform="matrix(0.24,0,0,0.24,700.3618,-207.76)"><text
149 
+           transform="matrix(1,0,0,-1,0,1558)"
150 150 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#a9d18e;fill-opacity:1;fill-rule:nonzero;stroke:none"
151 151 
            id="text118"><tspan
152 152 
              x="0 62.500019 125.00004"
153 153 
              y="0"
154 154 
              id="tspan116">TTG</tspan></text></g><g
155 155 
          id="g120"
156 
-         transform="matrix(0.24,0,0,0.24,47.57834,-158.16)"><text
157 
-           transform="matrix(1,0,0,-1,0,1500)"
156 
+         transform="matrix(0.24,0,0,0.24,47.57897,-206.08)"><text
157 
+           transform="matrix(1,0,0,-1,0,1558)"
158 158 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
159 159 
            id="text124"><tspan
160 160 
              x="0 43.23 72.885002 90.089996 149.97 189.52499 214.53"
161 161 
              y="0"
162 162 
              id="tspan122">Azimuth</tspan></text></g><g
163 163 
          id="g126"
164 
-         transform="matrix(0.24,0,0,0.24,932.1604,-126.24)"><text
165 
-           transform="matrix(1,0,0,-1,0,1500)"
164 
+         transform="matrix(0.24,0,0,0.24,931.6803,-177.28)"><text
165 
+           transform="matrix(1,0,0,-1,0,1558)"
166 166 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
167 167 
            id="text130"><tspan
168 168 
              x="0 38.017502 76.035004 114.9525"
169 169 
              y="0"
170 170 
              id="tspan128">23nt</tspan></text></g><g
171 171 
          id="g132"
172 
-         transform="matrix(0.24,0,0,0.24,932.1604,-159.84)"><text
173 
-           transform="matrix(1,0,0,-1,0,1500)"
172 
+         transform="matrix(0.24,0,0,0.24,931.6803,-207.76)"><text
173 
+           transform="matrix(1,0,0,-1,0,1558)"
174 174 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
175 175 
            id="text136"><tspan
176 176 
              x="0 38.017502 76.035004 114.9525"
177 177 
              y="0"
178 178 
              id="tspan134">30nt</tspan></text></g><g
179 179 
          id="g138"
180 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.4206,110.958)"><path
180 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.4206,77.7752)"><path
181 181 
            d="M 0,0 1303020,1"
182 182 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
183 183 
            id="path140" /></g><g
184 184 
          id="g142"
185 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,809.5659,110.958)"><path
185 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,809.5659,77.7752)"><path
186 186 
            d="M 0,0 1303020,1"
187 187 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
188 188 
            id="path144" /></g><g
189 189 
          id="g146"
190 
-         transform="matrix(0.24,0,0,0.24,236.2206,-257.28)"><text
191 
-           transform="matrix(1,0,0,-1,0,1500)"
190 
+         transform="matrix(0.24,0,0,0.24,236.2206,-304.24)"><text
191 
+           transform="matrix(1,0,0,-1,0,1558)"
192 192 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#a9d18e;fill-opacity:1;fill-rule:nonzero;stroke:none"
193 193 
            id="text150"><tspan
194 194 
              x="0 62.500019 125.00004 187.50006 250.00008 312.50009 375.00012 437.50015"
195 195 
              y="0"
196 196 
              id="tspan148">GTG…ACCT</tspan></text></g><g
197 197 
          id="g152"
198 
-         transform="matrix(0.24,0,0,0.24,356.2205,-257.28)"><text
199 
-           transform="matrix(1,0,0,-1,0,1500)"
198 
+         transform="matrix(0.24,0,0,0.24,356.2205,-304.24)"><text
199 
+           transform="matrix(1,0,0,-1,0,1558)"
200 200 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
201 201 
            id="text156"><tspan
202 202 
              x="0 62.500019 125.00004 187.50006 250.00008 312.50009 375.00012 437.50015 500.00015 562.50018 625.00018 687.50024 750.00024 812.50024 875.00031 937.50031"
203 203 
              y="0"
204 204 
              id="tspan154">ATCGATGCTGATGCTA</tspan></text></g><g
205 205 
          id="g158"
206 
-         transform="matrix(0.24,0,0,0.24,596.2205,-257.28)"><text
207 
-           transform="matrix(1,0,0,-1,0,1500)"
206 
+         transform="matrix(0.24,0,0,0.24,596.2205,-304.24)"><text
207 
+           transform="matrix(1,0,0,-1,0,1558)"
208 208 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
209 209 
            id="text162"><tspan
210 210 
              x="0"
211 211 
              y="0"
212 212 
              id="tspan160">G</tspan></text></g><g
213 213 
          id="g164"
214 
-         transform="matrix(0.24,0,0,0.24,611.2205,-257.28)"><text
215 
-           transform="matrix(1,0,0,-1,0,1500)"
214 
+         transform="matrix(0.24,0,0,0.24,611.2205,-304.24)"><text
215 
+           transform="matrix(1,0,0,-1,0,1558)"
216 216 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
217 217 
            id="text168"><tspan
218 218 
              x="0 62.500019 125.00004"
219 219 
              y="0"
220 220 
              id="tspan166">ATA</tspan></text></g><g
221 221 
          id="g170"
222 
-         transform="matrix(0.24,0,0,0.24,656.2205,-257.28)"><text
223 
-           transform="matrix(1,0,0,-1,0,1500)"
222 
+         transform="matrix(0.24,0,0,0.24,656.2205,-304.24)"><text
223 
+           transform="matrix(1,0,0,-1,0,1558)"
224 224 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
225 225 
            id="text174"><tspan
226 226 
              x="0"
227 227 
              y="0"
228 228 
              id="tspan172">A</tspan></text></g><g
229 229 
          id="g176"
230 
-         transform="matrix(0.24,0,0,0.24,671.2205,-257.28)"><text
231 
-           transform="matrix(1,0,0,-1,0,1500)"
230 
+         transform="matrix(0.24,0,0,0.24,671.2205,-304.24)"><text
231 
+           transform="matrix(1,0,0,-1,0,1558)"
232 232 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#c55a11;fill-opacity:1;fill-rule:nonzero;stroke:none"
233 233 
            id="text180"><tspan
234 234 
              x="0 62.500019"
235 235 
              y="0"
236 236 
              id="tspan178">GG</tspan></text></g><g
237 237 
          id="g182"
238 
-         transform="matrix(0.24,0,0,0.24,701.2205,-257.28)"><text
239 
-           transform="matrix(1,0,0,-1,0,1500)"
238 
+         transform="matrix(0.24,0,0,0.24,701.2205,-304.24)"><text
239 
+           transform="matrix(1,0,0,-1,0,1558)"
240 240 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#a9d18e;fill-opacity:1;fill-rule:nonzero;stroke:none"
241 241 
            id="text186"><tspan
242 242 
              x="0 62.500019 125.00004 187.50006 250.00008 312.50009 375.00012"
243 243 
              y="0"
244 244 
              id="tspan184">TTG…ATT</tspan></text></g><g
245 245 
          id="g188"
246 
-         transform="matrix(0.24,0,0,0.24,64.70366,-256.32)"><text
247 
-           transform="matrix(1,0,0,-1,0,1500)"
246 
+         transform="matrix(0.24,0,0,0.24,64.70397,-303.28)"><text
247 
+           transform="matrix(1,0,0,-1,0,1558)"
248 248 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
249 249 
            id="text192"><tspan
250 250 
              x="0 31.77 48.990002 88.559998 128.13 165.60001"
251 251 
              y="0"
252 252 
              id="tspan190">Lindel</tspan></text></g><g
253 253 
          id="g194"
254 
-         transform="matrix(0.24,0,0,0.24,932.1607,-256.8)"><text
255 
-           transform="matrix(1,0,0,-1,0,1500)"
254 
+         transform="matrix(0.24,0,0,0.24,931.6803,-304)"><text
255 
+           transform="matrix(1,0,0,-1,0,1558)"
256 256 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
257 257 
            id="text198"><tspan
258 258 
              x="0 38.017502 76.035004 114.9525"
259 259 
              y="0"
260 260 
              id="tspan196">65nt</tspan></text></g><g
261 261 
          id="g200"
262 
-         transform="matrix(0,7.874016e-5,7.874016e-5,0,702.8361,51.20459)"><path
262 
+         transform="matrix(0,7.874016e-5,7.874016e-5,0,702.8361,35.27654)"><path
263 263 
            d="m 369332,1338398 c -101988.6,0 -184666.7,-13779 -184666.7,-30777 l 1.4,-596951.3 c 0,-16997.7 -82678.1,-30777 -184666.7,-30777 101988.6,0 184666.7,-13779.3 184666.7,-30777 V 30777.01 C 184666.7,13779.33 267344.8,0 369333.4,0"
264 264 
            style="fill:none;stroke:#000000;stroke-width:6350;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
265 265 
            id="path202" /></g><g
266 266 
          id="g204"
267 
-         transform="matrix(0,7.874016e-5,7.874016e-5,0,239.6189,47.80407)"><path
267 
+         transform="matrix(0,7.874016e-5,7.874016e-5,0,239.6193,31.87602)"><path
268 268 
            d="m 409377,1438850 c -113046.3,0 -204688.5,-15273 -204688.5,-34113 V 765034.2 c 0,-18840 -91642.2,-34112.9 -204688.5,-34112.9 113046.3,0 204688.5,-15272.9 204688.5,-34112.9 V 34112.89 C 204688.5,15272.86 296330.7,0 409377,0"
269 269 
            style="fill:none;stroke:#000000;stroke-width:6350;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
270 270 
            id="path206" /></g><g
271 271 
          id="g208"
272 
-         transform="matrix(0,7.874016e-5,7.874016e-5,0,359.0259,46.94667)"><path
272 
+         transform="matrix(0,7.874016e-5,7.874016e-5,0,359.0263,31.01862)"><path
273 273 
            d="m 409080.4,3715436 c -112964.5,0 -204540.2,-15261 -204540.2,-34087 V 1921495 c 0,-18826 -91575.8,-34087 -204540.2,-34087 112964.4,0 204540.2,-15261 204540.2,-34087 V 34086.6 C 204540.2,15261.09 296115.9,0 409080.4,0"
274 274 
            style="fill:none;stroke:#000000;stroke-width:6350;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
275 275 
            id="path210" /></g><g
276 276 
          id="g212"
277 
-         transform="matrix(0,7.874016e-5,7.874016e-5,0,654.9509,51.76627)"><path
277 
+         transform="matrix(0,7.874016e-5,7.874016e-5,0,654.9512,35.83825)"><path
278 278 
            d="m 330521,565346 c -91270.8,0 -165260.5,-12331 -165260.5,-27542.1 V 314732.2 c 0,-15211.1 -73989.64,-27542.1 -165260.5,-27542.1 91270.86,0 165260.5,-12331 165260.5,-27542.1 V 27542.07 C 165260.5,12331 239250.2,0 330521,0"
279 279 
            style="fill:none;stroke:#000000;stroke-width:6350;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
280 280 
            id="path214" /></g><g
281 281 
          id="g216"
282 
-         transform="matrix(0.24,0,0,0.24,455.1106,-338.16)"><text
283 
-           transform="matrix(1,0,0,-1,0,1500)"
282 
+         transform="matrix(0.24,0,0,0.24,455.1106,-367.84)"><text
283 
+           transform="matrix(1,0,0,-1,0,1558)"
284 284 
            style="font-variant:normal;font-weight:normal;font-size:83.3333px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
285 285 
            id="text220"><tspan
286 286 
              x="0 38.541664 82.291664 122.39166 157.80833 199.47499 228.64166 247.39166 272.90833 315.09998 357.29166 400.26666 428.39166"
287 287 
              y="0"
288 288 
              id="tspan218">Spacer (20nt)</tspan></text></g><g
289 289 
          id="g222"
290 
-         transform="matrix(0.24,0,0,0.24,629.868,-338.16)"><text
291 
-           transform="matrix(1,0,0,-1,0,1500)"
290 
+         transform="matrix(0.24,0,0,0.24,629.8683,-367.84)"><text
291 
+           transform="matrix(1,0,0,-1,0,1558)"
292 292 
            style="font-variant:normal;font-weight:normal;font-size:83.3333px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
293 293 
            id="text226"><tspan
294 294 
              x="0 37.083332 85.5 156.83333 175.58333 201.08333 243.24998 286.25 314.41666"
295 295 
              y="0"
296 296 
              id="tspan224">PAM (3nt)</tspan></text></g><g
297 297 
          id="g228"
298 
-         transform="matrix(0.24,0,0,0.24,739.547,-338.16)"><text
299 
-           transform="matrix(1,0,0,-1,0,1500)"
298 
+         transform="matrix(0.24,0,0,0.24,739.5473,-367.84)"><text
299 
+           transform="matrix(1,0,0,-1,0,1558)"
300 300 
            style="font-variant:normal;font-weight:normal;font-size:83.3333px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
301 301 
            id="text232"><tspan
302 302 
              x="0 42.191666 84.383331 127.325"
303 303 
              y="0"
304 304 
              id="tspan230">29nt</tspan></text></g><g
305 305 
          id="g234"
306 
-         transform="matrix(0.24,0,0,0.24,272.1051,-338.16)"><text
307 
-           transform="matrix(1,0,0,-1,0,1500)"
306 
+         transform="matrix(0.24,0,0,0.24,272.1054,-367.84)"><text
307 
+           transform="matrix(1,0,0,-1,0,1558)"
308 308 
            style="font-variant:normal;font-weight:normal;font-size:83.3333px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
309 309 
            id="text238"><tspan
310 310 
              x="0 42.191666 84.383331 127.325"
311 311 
              y="0"
312 312 
              id="tspan236">13nt</tspan></text></g><g
313 313 
          id="g240"
314 
-         transform="matrix(0.24,0,0,0.24,355.1134,-93.35999)"><text
315 
-           transform="matrix(1,0,0,-1,0,1500)"
314 
+         transform="matrix(0.24,0,0,0.24,355.1134,-85.83999)"><text
315 
+           transform="matrix(1,0,0,-1,0,1558)"
316 316 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
317 317 
            id="text244"><tspan
318 318 
              x="0 62.500019 125.00004 187.50006 250.00008 312.50009 375.00012 437.50015 500.00015 562.50018 625.00018 687.50024 750.00024 812.50024 875.00031 937.50031"
319 319 
              y="0"
320 320 
              id="tspan242">ATCGATGCTGATGCTA</tspan></text></g><g
321 321 
          id="g246"
322 
-         transform="matrix(0.24,0,0,0.24,595.1134,-93.35999)"><text
323 
-           transform="matrix(1,0,0,-1,0,1500)"
322 
+         transform="matrix(0.24,0,0,0.24,595.1134,-85.83999)"><text
323 
+           transform="matrix(1,0,0,-1,0,1558)"
324 324 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
325 325 
            id="text250"><tspan
326 326 
              x="0"
327 327 
              y="0"
328 328 
              id="tspan248">G</tspan></text></g><g
329 329 
          id="g252"
330 
-         transform="matrix(0.24,0,0,0.24,610.1134,-93.35999)"><text
331 
-           transform="matrix(1,0,0,-1,0,1500)"
330 
+         transform="matrix(0.24,0,0,0.24,610.1134,-85.83999)"><text
331 
+           transform="matrix(1,0,0,-1,0,1558)"
332 332 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
333 333 
            id="text256"><tspan
334 334 
              x="0 62.500019 125.00004"
335 335 
              y="0"
336 336 
              id="tspan254">ATA</tspan></text></g><g
337 337 
          id="g258"
338 
-         transform="matrix(0.24,0,0,0.24,655.1134,-93.35999)"><text
339 
-           transform="matrix(1,0,0,-1,0,1500)"
338 
+         transform="matrix(0.24,0,0,0.24,655.1134,-85.83999)"><text
339 
+           transform="matrix(1,0,0,-1,0,1558)"
340 340 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
341 341 
            id="text262"><tspan
342 342 
              x="0"
343 343 
              y="0"
344 344 
              id="tspan260">A</tspan></text></g><g
345 345 
          id="g264"
346 
-         transform="matrix(0.24,0,0,0.24,670.1134,-93.35999)"><text
347 
-           transform="matrix(1,0,0,-1,0,1500)"
346 
+         transform="matrix(0.24,0,0,0.24,670.1134,-85.83999)"><text
347 
+           transform="matrix(1,0,0,-1,0,1558)"
348 348 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#c55a11;fill-opacity:1;fill-rule:nonzero;stroke:none"
349 349 
            id="text268"><tspan
350 350 
              x="0 62.500019"
351 351 
              y="0"
352 352 
              id="tspan266">GG</tspan></text></g><g
353 353 
          id="g270"
354 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.421,273.3188)"><path
354 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.4211,294.7755)"><path
355 355 
            d="M 0,0 2769397,1"
356 356 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
357 357 
            id="path272" /></g><g
358 358 
          id="g274"
359 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,707.01,273.3188)"><path
359 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,707.0102,294.7755)"><path
360 360 
            d="M 0,0 2605485,1"
361 361 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
362 362 
            id="path276" /></g><path
363 
-         d="m 664.6969,289.9535 v 24.5632 h -2.25 v -24.5632 z m 2.25,23.4382 -3.375,6.75 -3.375,-6.75 z"
363 
+         d="m 664.6969,311.4101 v 24.5632 h -2.25 v -24.5632 z m 2.25,23.4382 -3.375,6.75 -3.375,-6.7499 z"
364 364 
          style="fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
365 365 
          id="path278" /><g
366 366 
          id="g280"
367 
-         transform="matrix(0.24,0,0,0.24,629.8672,-32.87999)"><text
368 
-           transform="matrix(1,0,0,-1,0,1500)"
367 
+         transform="matrix(0.24,0,0,0.24,629.8672,-25.35999)"><text
368 
+           transform="matrix(1,0,0,-1,0,1558)"
369 369 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
370 370 
            id="text284"><tspan
371 371 
              x="0 33.022499 76.245003 140.3175 157.515 186.71249 203.91 228.0825"
372 372 
              y="0"
373 373 
              id="tspan282">PAM site</tspan></text></g><g
374 374 
          id="g286"
375 
-         transform="matrix(0.24,0,0,0.24,545.9901,-32.87999)"><text
376 
-           transform="matrix(1,0,0,-1,0,1500)"
375 
+         transform="matrix(0.24,0,0,0.24,545.9902,-25.35999)"><text
376 
+           transform="matrix(1,0,0,-1,0,1558)"
377 377 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
378 378 
            id="text290"><tspan
379 379 
              x="0 40.102501 79.68 104.7075 121.935 151.08749 168.24001 192.4425"
380 380 
              y="0"
381 381 
              id="tspan288">Cut site</tspan></text></g><path
382 
-         d="m 599.3637,288.7615 -12.8872,23.3899 1.9707,1.0858 12.8872,-23.3899 z m -14.315,21.3187 -0.3013,7.5407 6.2134,-4.2833 z"
382 
+         d="m 599.3638,310.2182 -12.8872,23.3899 1.9707,1.0858 12.8872,-23.3899 z m -14.315,21.3187 -0.3013,7.5407 6.2134,-4.2833 z"
383 383 
          style="fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
384 384 
          id="path292" /><g
385 385 
          id="g294"
386 
-         transform="matrix(0.24,0,0,0.24,9.549605,-88.79999)"><text
387 
-           transform="matrix(1,0,0,-1,0,1500)"
386 
+         transform="matrix(0.24,0,0,0.24,9.549605,-81.27999)"><text
387 
+           transform="matrix(1,0,0,-1,0,1558)"
388 388 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
389 389 
            id="text298"><tspan
390 390 
              x="0 22.92 61.439999 86.235001 125.805 150.075 189.645 218.78999 258.35999 294.32999 326.10001 363.57001 389.64001"
391 391 
              y="0"
392 392 
              id="tspan296">(Protospacer)</tspan></text></g><g
393 393 
          id="g300"
394 
-         transform="matrix(0.24,0,0,0.24,342.6961,-77.27999)"><text
395 
-           transform="matrix(1,0,0,-1,0,1500)"
394 
+         transform="matrix(0.24,0,0,0.24,342.6961,-69.75999)"><text
395 
+           transform="matrix(1,0,0,-1,0,1558)"
396 396 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
397 397 
            id="text304"><tspan
398 398 
              x="0 38.017502"
399 399 
              y="0"
400 400 
              id="tspan302">5’</tspan></text></g><g
401 401 
          id="g306"
402 
-         transform="matrix(0.24,0,0,0.24,706.6087,-77.27999)"><text
403 
-           transform="matrix(1,0,0,-1,0,1500)"
402 
+         transform="matrix(0.24,0,0,0.24,706.6088,-69.75999)"><text
403 
+           transform="matrix(1,0,0,-1,0,1558)"
404 404 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
405 405 
            id="text310"><tspan
406 406 
              x="0 38.017502"
407 407 
              y="0"
408 408 
              id="tspan308">3’</tspan></text></g><g
409 409 
          id="g312"
410 
-         transform="matrix(0.24,0,0,0.24,932.1603,-92.39999)"><text
411 
-           transform="matrix(1,0,0,-1,0,1500)"
410 
+         transform="matrix(0.24,0,0,0.24,932.1604,-84.87999)"><text
411 
+           transform="matrix(1,0,0,-1,0,1558)"
412 412 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
413 413 
            id="text316"><tspan
414 414 
              x="0 38.017502 76.035004 114.9525"
415 415 
              y="0"
416 416 
              id="tspan314">23nt</tspan></text></g><g
417 417 
          id="g318"
418 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.4206,177.7298)"><path
418 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.4206,143.5328)"><path
419 419 
            d="M 0,0 2054114,1"
420 420 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
421 421 
            id="path320" /></g><g
422 422 
          id="g322"
423 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,755.3,177.7298)"><path
423 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,755.3003,143.5328)"><path
424 424 
            d="M 0,0 1992203,1"
425 425 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
426 426 
            id="path324" /></g><g
427 427 
          id="g326"
428 
-         transform="matrix(0.24,0,0,0.24,295.3618,-189.36)"><text
429 
-           transform="matrix(1,0,0,-1,0,1500)"
428 
+         transform="matrix(0.24,0,0,0.24,295.3618,-237.52)"><text
429 
+           transform="matrix(1,0,0,-1,0,1558)"
430 430 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#a9d18e;fill-opacity:1;fill-rule:nonzero;stroke:none"
431 431 
            id="text330"><tspan
432 432 
              x="0 62.500019 125.00004 187.50006"
433 433 
              y="0"
434 434 
              id="tspan328">ACCT</tspan></text></g><g
435 435 
          id="g332"
436 
-         transform="matrix(0.24,0,0,0.24,355.3618,-189.36)"><text
437 
-           transform="matrix(1,0,0,-1,0,1500)"
436 
+         transform="matrix(0.24,0,0,0.24,355.3618,-237.52)"><text
437 
+           transform="matrix(1,0,0,-1,0,1558)"
438 438 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
439 439 
            id="text336"><tspan
440 440 
              x="0 62.500019 125.00004 187.50006 250.00008 312.50009 375.00012 437.50015 500.00015 562.50018 625.00018 687.50024 750.00024 812.50024 875.00031 937.50031"
441 441 
              y="0"
442 442 
              id="tspan334">ATCGATGCTGATGCTA</tspan></text></g><g
443 443 
          id="g338"
444 
-         transform="matrix(0.24,0,0,0.24,595.3618,-189.36)"><text
445 
-           transform="matrix(1,0,0,-1,0,1500)"
444 
+         transform="matrix(0.24,0,0,0.24,595.3618,-237.52)"><text
445 
+           transform="matrix(1,0,0,-1,0,1558)"
446 446 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
447 447 
            id="text342"><tspan
448 448 
              x="0"
449 449 
              y="0"
450 450 
              id="tspan340">G</tspan></text></g><g
451 451 
          id="g344"
452 
-         transform="matrix(0.24,0,0,0.24,610.3618,-189.36)"><text
453 
-           transform="matrix(1,0,0,-1,0,1500)"
452 
+         transform="matrix(0.24,0,0,0.24,610.3618,-237.52)"><text
453 
+           transform="matrix(1,0,0,-1,0,1558)"
454 454 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
455 455 
            id="text348"><tspan
456 456 
              x="0 62.500019 125.00004"
457 457 
              y="0"
458 458 
              id="tspan346">ATA</tspan></text></g><g
459 459 
          id="g350"
460 
-         transform="matrix(0.24,0,0,0.24,655.3618,-189.36)"><text
461 
-           transform="matrix(1,0,0,-1,0,1500)"
460 
+         transform="matrix(0.24,0,0,0.24,655.3618,-237.52)"><text
461 
+           transform="matrix(1,0,0,-1,0,1558)"
462 462 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
463 463 
            id="text354"><tspan
464 464 
              x="0"
465 465 
              y="0"
466 466 
              id="tspan352">A</tspan></text></g><g
467 467 
          id="g356"
468 
-         transform="matrix(0.24,0,0,0.24,670.3618,-189.36)"><text
469 
-           transform="matrix(1,0,0,-1,0,1500)"
468 
+         transform="matrix(0.24,0,0,0.24,670.3618,-237.52)"><text
469 
+           transform="matrix(1,0,0,-1,0,1558)"
470 470 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#c55a11;fill-opacity:1;fill-rule:nonzero;stroke:none"
471 471 
            id="text360"><tspan
472 472 
              x="0 62.500019"
473 473 
              y="0"
474 474 
              id="tspan358">GG</tspan></text></g><g
475 475 
          id="g362"
476 
-         transform="matrix(0.24,0,0,0.24,700.3618,-189.36)"><text
477 
-           transform="matrix(1,0,0,-1,0,1500)"
476 
+         transform="matrix(0.24,0,0,0.24,700.3618,-237.52)"><text
477 
+           transform="matrix(1,0,0,-1,0,1558)"
478 478 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#a9d18e;fill-opacity:1;fill-rule:nonzero;stroke:none"
479 479 
            id="text366"><tspan
480 480 
              x="0 62.500019 125.00004"
481 481 
              y="0"
482 482 
              id="tspan364">TTG</tspan></text></g><g
483 483 
          id="g368"
484 
-         transform="matrix(0.24,0,0,0.24,43.92335,-187.92)"><text
485 
-           transform="matrix(1,0,0,-1,0,1500)"
484 
+         transform="matrix(0.24,0,0,0.24,43.92398,-236.08)"><text
485 
+           transform="matrix(1,0,0,-1,0,1558)"
486 486 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
487 487 
            id="text372"><tspan
488 488 
              x="0 40.627499 80.205002 97.432503 134.91 169.3125 206.41499 231.4425"
489 489 
              y="0"
490 490 
              id="tspan370">RuleSet1</tspan></text></g><g
491 491 
          id="g374"
492 
-         transform="matrix(0.24,0,0,0.24,932.1604,-189.6)"><text
493 
-           transform="matrix(1,0,0,-1,0,1500)"
492 
+         transform="matrix(0.24,0,0,0.24,931.6803,-237.76)"><text
493 
+           transform="matrix(1,0,0,-1,0,1558)"
494 494 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
495 495 
            id="text378"><tspan
496 496 
              x="0 38.017502 76.035004 114.9525"
497 497 
              y="0"
498 498 
              id="tspan376">30nt</tspan></text></g><g
499 499 
          id="g380"
500 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.4206,145.6336)"><path
500 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.4206,111.4367)"><path
501 501 
            d="M 0,0 1758754,1"
502 502 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
503 503 
            id="path382" /></g><g
504 504 
          id="g384"
505 
-         transform="matrix(7.874016e-5,0,0,-7.874016e-5,792.8055,145.6336)"><path
505 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,792.8058,111.4367)"><path
506 506 
            d="M 0,0 1515883,1"
507 507 
            style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
508 508 
            id="path386" /></g><g
509 509 
          id="g388"
510 
-         transform="matrix(0.24,0,0,0.24,266.6859,-221.52)"><text
511 
-           transform="matrix(1,0,0,-1,0,1500)"
510 
+         transform="matrix(0.24,0,0,0.24,266.6859,-269.68)"><text
511 
+           transform="matrix(1,0,0,-1,0,1558)"
512 512 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#a9d18e;fill-opacity:1;fill-rule:nonzero;stroke:none"
513 513 
            id="text392"><tspan
514 514 
              x="0 62.500019 125.00004 187.50006 250.00008 312.50009"
515 515 
              y="0"
516 516 
              id="tspan390">AAACCT</tspan></text></g><g
517 517 
          id="g394"
518 
-         transform="matrix(0.24,0,0,0.24,356.6859,-221.52)"><text
519 
-           transform="matrix(1,0,0,-1,0,1500)"
518 
+         transform="matrix(0.24,0,0,0.24,356.6859,-269.68)"><text
519 
+           transform="matrix(1,0,0,-1,0,1558)"
520 520 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
521 521 
            id="text398"><tspan
522 522 
              x="0 62.500019 125.00004 187.50006 250.00008 312.50009 375.00012 437.50015 500.00015 562.50018 625.00018 687.50024 750.00024 812.50024 875.00031 937.50031"
523 523 
              y="0"
524 524 
              id="tspan396">ATCGATGCTGATGCTA</tspan></text></g><g
525 525 
          id="g400"
526 
-         transform="matrix(0.24,0,0,0.24,596.6859,-221.52)"><text
527 
-           transform="matrix(1,0,0,-1,0,1500)"
526 
+         transform="matrix(0.24,0,0,0.24,596.6859,-269.68)"><text
527 
+           transform="matrix(1,0,0,-1,0,1558)"
528 528 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
529 529 
            id="text404"><tspan
530 530 
              x="0"
531 531 
              y="0"
532 532 
              id="tspan402">G</tspan></text></g><g
533 533 
          id="g406"
534 
-         transform="matrix(0.24,0,0,0.24,611.6859,-221.52)"><text
535 
-           transform="matrix(1,0,0,-1,0,1500)"
534 
+         transform="matrix(0.24,0,0,0.24,611.6859,-269.68)"><text
535 
+           transform="matrix(1,0,0,-1,0,1558)"
536 536 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
537 537 
            id="text410"><tspan
538 538 
              x="0 62.500019 125.00004"
539 539 
              y="0"
540 540 
              id="tspan408">ATA</tspan></text></g><g
541 541 
          id="g412"
542 
-         transform="matrix(0.24,0,0,0.24,656.6859,-221.52)"><text
543 
-           transform="matrix(1,0,0,-1,0,1500)"
542 
+         transform="matrix(0.24,0,0,0.24,656.6859,-269.68)"><text
543 
+           transform="matrix(1,0,0,-1,0,1558)"
544 544 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
545 545 
            id="text416"><tspan
546 546 
              x="0"
547 547 
              y="0"
548 548 
              id="tspan414">A</tspan></text></g><g
549 549 
          id="g418"
550 
-         transform="matrix(0.24,0,0,0.24,671.6859,-221.52)"><text
551 
-           transform="matrix(1,0,0,-1,0,1500)"
550 
+         transform="matrix(0.24,0,0,0.24,671.6859,-269.68)"><text
551 
+           transform="matrix(1,0,0,-1,0,1558)"
552 552 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#c55a11;fill-opacity:1;fill-rule:nonzero;stroke:none"
553 553 
            id="text422"><tspan
554 554 
              x="0 62.500019"
555 555 
              y="0"
556 556 
              id="tspan420">GG</tspan></text></g><g
557 557 
          id="g424"
558 
-         transform="matrix(0.24,0,0,0.24,701.6859,-221.52)"><text
559 
-           transform="matrix(1,0,0,-1,0,1500)"
558 
+         transform="matrix(0.24,0,0,0.24,701.6859,-269.68)"><text
559 
+           transform="matrix(1,0,0,-1,0,1558)"
560 560 
            style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#a9d18e;fill-opacity:1;fill-rule:nonzero;stroke:none"
561 561 
            id="text428"><tspan
562 562 
              x="0 62.500019 125.00004 187.50006 250.00008 312.50009"
563 563 
              y="0"
564 564 
              id="tspan426">TTGGGC</tspan></text></g><g
565 565 
          id="g430"
566 
-         transform="matrix(0.24,0,0,0.24,24.85968,-219.84)"><text
567 
-           transform="matrix(1,0,0,-1,0,1500)"
566 
+         transform="matrix(0.24,0,0,0.24,24.85968,-268)"><text
567 
+           transform="matrix(1,0,0,-1,0,1558)"
568 568 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
569 569 
            id="text434"><tspan
570 570 
              x="0 40.102501 80.730003 99.457497 133.86 172.3875 213.015 242.1675 273.345 309.2475"
571 571 
              y="0"
572 572 
              id="tspan432">CRISPRscan</tspan></text></g><g
573 573 
          id="g436"
574 
-         transform="matrix(0.24,0,0,0.24,932.1604,-221.76)"><text
575 
-           transform="matrix(1,0,0,-1,0,1500)"
574 
+         transform="matrix(0.24,0,0,0.24,931.6803,-269.68)"><text
575 
+           transform="matrix(1,0,0,-1,0,1558)"
576 576 
            style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
577 577 
            id="text440"><tspan
578 578 
              x="0 38.017502 76.035004 114.9525"
579 579 
              y="0"
580 
-             id="tspan438">35nt</tspan></text></g></g></g></svg>
580 
+             id="tspan438">35nt</tspan></text></g><g
581 
+         id="g442"
582 
+         transform="matrix(0.24,0,0,0.24,354.9446,-146.8)"><text
583 
+           transform="matrix(1,0,0,-1,0,1558)"
584 
+           style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
585 
+           id="text446"><tspan
586 
+             x="0 62.500019 125.00004 187.50006 250.00008 312.50009 375.00012 437.50015 500.00015 562.50018 625.00018 687.50024 750.00024 812.50024 875.00031 937.50031"
587 
+             y="0"
588 
+             id="tspan444">ATCGATGCTGATGCTA</tspan></text></g><g
589 
+         id="g448"
590 
+         transform="matrix(0.24,0,0,0.24,594.9446,-146.8)"><text
591 
+           transform="matrix(1,0,0,-1,0,1558)"
592 
+           style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
593 
+           id="text452"><tspan
594 
+             x="0"
595 
+             y="0"
596 
+             id="tspan450">G</tspan></text></g><g
597 
+         id="g454"
598 
+         transform="matrix(0.24,0,0,0.24,609.9446,-146.8)"><text
599 
+           transform="matrix(1,0,0,-1,0,1558)"
600 
+           style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
601 
+           id="text458"><tspan
602 
+             x="0 62.500019 125.00004"
603 
+             y="0"
604 
+             id="tspan456">ATA</tspan></text></g><g
605 
+         id="g460"
606 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,126.2522,234.0017)"><path
607 
+           d="M 0,0 2785439,1"
608 
+           style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
609 
+           id="path462" /></g><g
610 
+         id="g464"
611 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,663.5721,234.0017)"><path
612 
+           d="M 0,0 3155003,1"
613 
+           style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
614 
+           id="path466" /></g><g
615 
+         id="g468"
616 
+         transform="matrix(0.24,0,0,0.24,27.76953,-143.92)"><text
617 
+           transform="matrix(1,0,0,-1,0,1558)"
618 
+           style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
619 
+           id="text472"><tspan
620 
+             x="0 40.102501 80.730003 99.457497 133.86 172.3875 213.015 248.24249 272.44501 309.92249"
621 
+             y="0"
622 
+             id="tspan470">CRISPRater</tspan></text></g><g
623 
+         id="g474"
624 
+         transform="matrix(0.24,0,0,0.24,931.9916,-146.8)"><text
625 
+           transform="matrix(1,0,0,-1,0,1558)"
626 
+           style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
627 
+           id="text478"><tspan
628 
+             x="0 38.017502 76.035004 114.9525"
629 
+             y="0"
630 
+             id="tspan476">20nt</tspan></text></g><g
631 
+         id="g480"
632 
+         transform="matrix(0.24,0,0,0.24,369.6331,-116.32)"><text
633 
+           transform="matrix(1,0,0,-1,0,1558)"
634 
+           style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
635 
+           id="text484"><tspan
636 
+             x="0 62.500019 125.00004 187.50006 250.00008 312.50009 375.00012 437.50015 500.00015 562.50018 625.00018 687.50024 750.00024 812.50024 875.00031"
637 
+             y="0"
638 
+             id="tspan482">TCGATGCTGATGCTA</tspan></text></g><g
639 
+         id="g486"
640 
+         transform="matrix(0.24,0,0,0.24,594.633,-116.32)"><text
641 
+           transform="matrix(1,0,0,-1,0,1558)"
642 
+           style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
643 
+           id="text490"><tspan
644 
+             x="0"
645 
+             y="0"
646 
+             id="tspan488">G</tspan></text></g><g
647 
+         id="g492"
648 
+         transform="matrix(0.24,0,0,0.24,609.633,-116.32)"><text
649 
+           transform="matrix(1,0,0,-1,0,1558)"
650 
+           style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ffd966;fill-opacity:1;fill-rule:nonzero;stroke:none"
651 
+           id="text496"><tspan
652 
+             x="0 62.500019 125.00004"
653 
+             y="0"
654 
+             id="tspan494">ATA</tspan></text></g><g
655 
+         id="g498"
656 
+         transform="matrix(0.24,0,0,0.24,654.633,-116.32)"><text
657 
+           transform="matrix(1,0,0,-1,0,1558)"
658 
+           style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#ff0000;fill-opacity:1;fill-rule:nonzero;stroke:none"
659 
+           id="text502"><tspan
660 
+             x="0"
661 
+             y="0"
662 
+             id="tspan500">A</tspan></text></g><g
663 
+         id="g504"
664 
+         transform="matrix(0.24,0,0,0.24,669.633,-116.32)"><text
665 
+           transform="matrix(1,0,0,-1,0,1558)"
666 
+           style="font-variant:normal;font-weight:normal;font-size:104.167px;font-family:Courier;-inkscape-font-specification:Courier;writing-mode:lr-tb;fill:#c55a11;fill-opacity:1;fill-rule:nonzero;stroke:none"
667 
+           id="text508"><tspan
668 
+             x="0 62.500019"
669 
+             y="0"
670 
+             id="tspan506">GG</tspan></text></g><g
671 
+         id="g510"
672 
+         transform="matrix(7.874016e-5,0,0,7.874016e-5,125.9409,264.4457)"><path
673 
+           d="M 0,0 2972553,1315"
674 
+           style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
675 
+           id="path512" /></g><g
676 
+         id="g514"
677 
+         transform="matrix(7.874016e-5,0,0,-7.874016e-5,709.0563,264.4458)"><path
678 
+           d="M 0,0 2573401,1"
679 
+           style="fill:none;stroke:#000000;stroke-width:22225;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:8;stroke-dasharray:none;stroke-opacity:1"
680 
+           id="path516" /></g><g
681 
+         id="g518"
682 
+         transform="matrix(0.24,0,0,0.24,44.70398,-113.44)"><text
683 
+           transform="matrix(1,0,0,-1,0,1558)"
684 
+           style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
685 
+           id="text522"><tspan
686 
+             x="0 40.102501 80.730003 99.457497 133.86 172.3875 213.015 248.9175"
687 
+             y="0"
688 
+             id="tspan520">CRISPRai</tspan></text></g><g
689 
+         id="g524"
690 
+         transform="matrix(0.24,0,0,0.24,931.6803,-112)"><text
691 
+           transform="matrix(1,0,0,-1,0,1558)"
692 
+           style="font-variant:normal;font-weight:normal;font-size:75px;font-family:Calibri;-inkscape-font-specification:Calibri;writing-mode:lr-tb;fill:#000000;fill-opacity:1;fill-rule:nonzero;stroke:none"
693 
+           id="text528"><tspan
694 
+             x="0 38.017502 76.035004 114.9525"
695 
+             y="0"
696 
+             id="tspan526">22nt</tspan></text></g></g></g></svg>
vignettes/references.bib
History View file @ 6f2475d
... ... 
@@ -1,3 +1,34 @@
1 
+@article{crisprai,
2 
+  title={Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation},
3 
+  author={Horlbeck, Max A and Gilbert, Luke A and Villalta, Jacqueline E and Adamson, Britt and Pak, Ryan A and Chen, Yuwen and Fields, Alexander P and Park, Chong Yon and Corn, Jacob E and Kampmann, Martin and others},
4 
+  journal={elife},
5 
+  volume={5},
6 
+  year={2016},
7 
+  publisher={eLife Sciences Publications, Ltd}
8 
+}
9 
+
10 
+@article{casrxrf,
11 
+  title={Massively parallel Cas13 screens reveal principles for guide RNA design},
12 
+  author={Wessels, Hans-Hermann and M{\'e}ndez-Mancilla, Alejandro and Guo, Xinyi and Legut, Mateusz and Daniloski, Zharko and Sanjana, Neville E},
13 
+  journal={Nature biotechnology},
14 
+  volume={38},
15 
+  number={6},
16 
+  pages={722--727},
17 
+  year={2020},
18 
+  publisher={Nature Publishing Group}
19 
+}
20 
+
21 
+@article{crisprater,
22 
+  title={Refined sgRNA efficacy prediction improves large-and small-scale CRISPR--Cas9 applications},
23 
+  author={Labuhn, Maurice and Adams, Felix F and Ng, Michelle and Knoess, Sabine and Schambach, Axel and Charpentier, Emmanuelle M and Schwarzer, Adrian and Mateo, Juan L and Klusmann, Jan-Henning and Heckl, Dirk},
24 
+  journal={Nucleic acids research},
25 
+  volume={46},
26 
+  number={3},
27 
+  pages={1375--1385},
28 
+  year={2018},
29 
+  publisher={Oxford University Press}
30 
+}
31 
+
1 32 
 @article{crisprscan,
2 33 
   title={CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo},
3 34 
   author={Moreno-Mateos, Miguel A and Vejnar, Charles E and Beaudoin, Jean-Denis and Fernandez, Juan P and Mis, Emily K and Khokha, Mustafa K and Giraldez, Antonio J},