CHANGES IN VERSION 1.44.1
     o added support for bulge detection by integrating Cas-OFFinder.
     o tidied up most codes and modularized offTargetAnalysis().
     o updated documentation and vignettes using Bioconductor style.
     o removed a few redundant/unnecessary parameters.
     o other minor bugs fixed.
CHANGES IN VERSION 1.29.2
     o added parameters such as predIndelFreq to allow the prediction of indels and their frequecies for Cas9 targeted sites
CHANGES IN VERSION 1.29.1
     o added parameter calculategRNAefficacyForOfftargets, default to TRUE.
CHANGES IN VERSION 1.25.9
     o added parameters allowing gRNA design for base editor system
CHANGES IN VERSION 1.25.6
     o added parameter ignore.strand to indidate whether gene annotation should be strand-specific
CHANGES IN VERSION 1.25.5
     o efficacy is calculated only for on-target 
CHANGES IN VERSION 1.25.4
     o annotation is now strand-specific 

------------------------
CHANGES IN VERSION 1.25.1
------------------------

NEW FEATURES

     o added paired.orientation parameteter

CHANGES IN VERSION 1.9.12
------------------------

NEW FEATURES

     o added annotatePaired parameter
     o added parallel processing 

CHANGES IN VERSION 1.9.6
------------------------

NEW FEATURES

     o added offTargetAnalysisOfPeakRegions function for GUIDE-seq analysis

offTargetAnalysisOfPeakRegions

CHANGES IN VERSION 1.9.3
------------------------

NEW FEATURES

     o support bed format inputFilePath for compare2Sequences 
     o added upstream and downstream parameters to compare2Sequences for bed input file
     o added upstream.search and downstream.search in offTargetAnalysis for bed input file
     o these features are particularly useful for annotating GUIDE-seq peaks 
 
CHANGES IN VERSION 1.9.2
------------------------

NEW FEATURES

     o summary file will contain all input gRNAs even there is no on target in the searching genome. This feature is useful to search for offtarget in a different genome 
     o support bed format inputFilePath for offTargetAnalysis 

CHANGES IN VERSION 1.9.1
------------------------

NEW FEATURES

     o added parameter allowed.mismatch.PAM to specify the number of degenerative bases in the PAM sequence. This feature is useful for specifying different PAM.pattern for offtarget search.

CHANGES IN VERSION 1.7.6
------------------------

NEW FEATURES

     o added parameter foldgRNA to calculate the minimum free energy (mfe) of the secondary structure of the gRNA with gRNA backbone sequence. In addition, summary file also includes the difference of mfe between the secondary structure of gRNA backbone alone and the secondary structure of gRNA backbone with the variable region of the gRNA, and the bracket notation of the secondary structure of gRNA backbone with the variable region of the gRNA to facilitate gRNA selection. 

CHANGES IN VERSION 1.7.3
------------------------

NEW FEATURES

     o added parameter chromToExclude in offTargetAnalysis to specify chromosomes not to search for offtargets, which can be used to exclude haplotype blocks


CHANGES IN VERSION 1.7.1
------------------------

BUG FIXES

     o only search for gRNAs for input sequences longer than gRNA.size plus PAM size 


CHANGES IN VERSION 1.5.6
------------------------

NEW FEATURES

     o added uniqueREsfor200total and uniqueREsfor100total in summary file to output RE sites that is unique in the 200 and 100 bp flanking gRNA region


CHANGES IN VERSION 1.5.5
------------------------

NEW FEATURES

     o added useEfficacyFromInputSeq parameter in offTargetAnalysis function to allow user to select whether to use the gRNA efficacy calculated from the input sequence or the one from off-target analysis. This is useful when the input sequence is from a genome that is different from the off-target analysis genome 

CHANGES IN VERSION 1.5.4
------------------------

NEW FEATURES

     o rename the gRNAs containing Cas9 cut site instead of gRNA start end end. Also output the cut sites in genbank file 


CHANGES IN VERSION 1.5.3
------------------------

NEW FEATURES

     o gRNA efficacy is calcualted for compare2Sequence function and for offTargetAnalysis with chromToSearch="" 

CHANGES IN VERSION 1.5.2
------------------------

NEW FEATURES

     o filter gRNAs with one or both cut site overlap with RE pattern 

CHANGES IN VERSION 1.5.1
------------------------

NEW FEATURES

     o annotateOfftargets is separated from filterOfftarget function and is faster as well

CHANGES IN VERSION 1.3.10
------------------------

NEW FEATURES

     o gRNAs are automatically output to a bed file for view in the UCSC genome browser 

CHANGES IN VERSION 1.3.8
------------------------

NEW FEATURES

     o Added calculategRNAefficiency to calculate gRNA cleavage efficiency using DoenchNBT2014 predictive logistic model

CHANGES IN VERSION 1.3.7
------------------------

NEW FEATURES

     o Added searchDirection to compare2Sequences to allow search one against the other and many to many sequence search
     o Added exception handling to catch no gRNA found error in compare2Sequences


CHANGES IN VERSION 1.3.5
------------------------

BUG FIXES

     o TopN offtarget total score was sometimes missing for sequences containing gRNAs with less than 6 offtargets in version 1.3.3 



CHANGES IN VERSION 1.3.3
------------------------

NEW FEATURES

     o Search for off-targets is much faster when more than 10 gRNAs are searched 
     o Added new optional parameter orgAnn in offTargetAnalysis 
     o Added gene ID and optional gene symbol in off-target output file 
     o Added gRNA target region, GC content of gRNA and number of Ts in the last 4 postion of gRNA (not including PAM sequence) in the summary output file

