Version 1.2.0: October 10, 2023
-------------------------------------------------------------------------------

General:

+ Updated dependencies: alakazam >= 1.3.0, ggplot2 >= 3.4.0, igraph >= 1.5.0.
+ As of `alakazam 1.3.0`, `alakazam::makeChangeoClone` requires the parameter 
  `locus` with default value `locus`. This function is used in some examples and
  tests in `shazam`. We added a `locus` column to the package's example data.

Distance Profiling:

+ Added to `distToNearest` the parameter `locusValues=c("IGH")` to specify loci
  values to focus the analysis on.
+ Fixed a bug in `distToNearest` where  grouping by `fields` was applied 
  after grouping by genes, therefore not treating independently the different 
  subsets of data to identify groups of genes. In practice, this means that
  if fields was set to treat samples independently (`fields='sample_id'`), 
  single linkage was applied to all data, and two genes could be placed in the 
  same group of genes if they where connected by an ambiguous gene call in any 
  of the samples. Now, data is separated by `fields`(sample_id in this example)
  before creating the groups of genes, and ambiguities in other samples are not 
  considered.

Version 1.1.2: September 26, 2022
-------------------------------------------------------------------------------

Mutation Profiling:

+ Bug fix in parallelization set up for functions `slideWindowTune` 
  and `slideWindowDb`.
  
+ `plotSlideWindowTune` (`slideWindowTunePlot`). Updated the possible
   values of the parameter `plotFiltered`, for easier usage. The new values 
   (and their equivalent values in `slideWindowTunePlot`) are `filtered` (`TRUE`), 
   `remaining` (`FALSE`), and `per_mutation` (`NULL`). 
  
Deprecated:

  + Deprecated `slideWindowTunePlot` in favor of `plotSlideWindowTune`, for naming
  consistency.

Version 1.1.1: May 23, 2022
-------------------------------------------------------------------------------

General:

+ Removed dependency: kedd. The CRAN kedd package (by Arsalane Chouaib Guidoum) 
  has been scheduled for archival on 2022-05-25. We have adapted the functions
  used by shazam and removed the dependency.
  
New feature:

+ Added the function `convertNumbering` to convert between numbering systems (IMGT, Kabat).

Mutation Profiling:

+ `shmulateTree` has new argument `nproc` to specify the number of cores. Default
   values `mutThresh` and `windowSize` have been set to `mutThresh=6` and
   `windowSize=10`.
   
+ Added the option `plotFiltered=NULL` to `slideWindowTunePlot`.
   
+ Fixed a bug in `listObservedMutations` not returning a list when `db` had
  one sequence with one mutation.
  
+ Fixed bars shifted in `plotMutability`.


Version 1.1.0: July 8, 2021
-------------------------------------------------------------------------------

General:

+ Updated dependencies to alakazam >= 1.1.0 and ggplot2 >= 3.3.4.

Selection Analysis:

+ `observedMutations`, `expectedMutations`, and `calcBaseline` can analyze 
  mutations in all regions (CDR1, CDR2, CDR3, FWR1, FWR2, FWR3 and FWR4) by 
  specifying `regionDefinition=IMGT_VDJ` or 
  `regionDefinition=IMGT_VDJ_BY_REGIONS`.
+ Added the function `setRegionBoundaries` to build sequence-specific 
  `RegionDefinition` objects extending to CDR3 and FWR4.
+ Added the function `makeGraphDf` to facilitate mutational analysis on 
  lineage trees.

Distance Profiling:

+ Fixed a bug in `distToNearest` where TRB and TRD sequences where ignored in 
  distance calculation.
+ Fixed a bug in `distToNearest` causing a fatal error when `cross` was set.
+ Fixed a bug in `nearestDist` causing a fatal error when using `model="aa"` 
  and `crossGroups`.

Targeting Models:

+ Fixed an incompatibility with newer versions of ggplot2 in `plotMutability`.


Version 1.0.2: August 10, 2020
-------------------------------------------------------------------------------

Mutation Profiling:

+ Fixed a bug in `observedMutations` and `calcObservedMutations` causing 
  mutation counting to fail when there are gap (`-`) characters in the 
  germline sequence.

Targeting Models:

+ Fixed a bug in `createTargetingModel` causing empty counts in the 
  `numMutS` and `numMutR` slots.


Version 1.0.1: July 18, 2020
-------------------------------------------------------------------------------

Distance Profiling:

+ Added support for TCR genes to `distToNearest`. 
+ Renamed the `groupUsingOnlyIGH` argument of `distToNearest` to `onlyHeavy`.


Version 1.0.0 May 9, 2020
-------------------------------------------------------------------------------

Backwards Incompatible Changes:

+ Changed default expected data format from the Change-O data format to the
  AIRR Rearrangement standard. For example: where functions used the column 
  name `V_CALL` (Change-O) as the default to identify the field that stored 
  the V gene calls, they now use `v_call` (AIRR). That means, scripts that 
  relied on default values (previously, `v_call="V_CALL"`), will now fail if 
  calls to the functions are not updated to reflect the correct value for the 
  data. If data are in the Change-O format, the current default value 
  `v_call="v_call"` will fail to identify the column with the V gene calls
  as the column `v_call` doesn't exist. In this case, `v_call="V_CALL"` needs 
  to be specified in the function call.
+ `ExampleDb` converted to the AIRR Rearrangement standard and examples 
  updated accordingly.
+ For consistency with the style of the new data format default, other field 
  names have been updated to use the same capitalization. This change affects:
    - Region definitions. For example, the `labels` slot of `IMGT_V` has 
      changed from `CDR_R`, `CDR_S`, `FWR_R` and `FWR_S` to `cdr_r`, `cdr_s`, 
      `fwr_r` and `fwr_s`, respectively.
    - Mutations in `CODON_TABLE` and the different `MUTATION_SCHEMES` change
      from `R`, `S` and `Stop` to `r`, `s` and `stop`, respectively. 
    - Mutation profiling function output columns. For example, from 
      `MU_COUNT_SEQ` to `mu_count_seq`.
    - `calcBaseline` and related function output columns and S4 object slots. 
      For example, from `PVALUE`, `REGION` and `BASELINE_CI_PVALUE` to 
      `pvalue`, `region` and `baseline_ci_pvalue`, respectively.
 + Model names used by `createSubstitutionMatrix`, `createMutabilityMatrix` and 
   `createTargetingModel`, changed from `model=c("S","RS")` to 
   `model=c("s","rs")`.

General:

+ License changed to AGPL-3.

Targeting Models:

+ `createMutabilityMatrix`, `extendMutabilityMatrix`, `createTargetingMatrix`,
  and `createTargetingModel` now also returns the numbers of silent and
  replacement mutations used for estimating the 5-mer mutabilities. These 
  numbers are recorded in the `numMutS` and `numMutR` slots in the newly
  defined `MutabilityModel`, `MutabilityModelWithSource`, and `TargetingMatrix` 
  classes.
  
Mutation Profiling:

+ `shmulateSeq` now also supports specifying the frequency of mutations to be 
   introduced. (Previously, only the number of mutations was supported.)


Version 0.2.3 February 5, 2020
-------------------------------------------------------------------------------

General:

+ Removed SDMTools dependency.


Version 0.2.2 December 15, 2019
-------------------------------------------------------------------------------

General:

+ Fixed an incompatibility with R 4.0 matrix changes.

Version 0.2.1 July 19, 2019
-------------------------------------------------------------------------------

Distance Calculation:

+ Fixed a bug in `distToNearest` that could potentially cause sequences from
  different partitions to be used for distance calculation. 


Version 0.2.0 July 18, 2019
-------------------------------------------------------------------------------

General:

+ Upgraded to alakazam >= 0.3.0 and dplyr >= 0.8.1.

Distance Calculation:

+ Fixed a bug in `plotDensityThreshold` for negative densities.
+ Fixed a bug in `distToNearest` for performing subsampling while calculating
  cross-group nearest neighbor distances.
+ For partitioning sequences, `distToNearest` now supports, via a new argument
  `VJthenLen`, either a 2-stage partitioning (first by V gene and J gene, then 
  by junction length), or a 1-stage partitioning (simultaneously by V gene, J 
  gene, and junction length). For 1-stage partitioning, `distToNearest` supports
  export of the partitioning information as a new column via `keepVJLgroup`.
+ `distToNearest` now supports single-cell input data with the addition of new
  arguments `cellIdColumn`, `locusColumn`, and `groupUsingOnlyIGH`.

Mutation Profiling:

+ `shmulateTree` has new arguments, `start` and `end`, to specify the region
  in the sequence where mutations can be introduced. 

Selection Analysis:

+ Added the function `consensusSequence` which can be used to build a 
  consensus sequence using a variety of methods.


Version 0.1.11: January 27, 2019
-------------------------------------------------------------------------------

General:

+ Fixed a bug in the prototype declarations for the `TargetingModel` and 
  `RegionDefinition` S4 classes.


Version 0.1.10: September 19, 2018
-------------------------------------------------------------------------------

General:

+ Added `subsample` argument to `distToNearest` function.
+ Removed some internal utility functions in favor of importing them from 
  `alakazam`. Specifically, `progressBar`, `getBaseTheme` and `checkColumns`.
+ Removed `clearConsole`, `getnproc`, and `getPlatform` functions.

Distance Calculation:

+ Changed default `findThreshold` method to `density`.
+ Significantly reduced run time of the `density` method by retuning the 
  bandwidth detection process. The `density` method should now also yield more 
  consistent thresholds, on average.
+ The `subsample` argument to `findThreshold` now applies to both the 
  `density` and `gmm` methods. Subsampling of distance is not performed by 
  default.
+ Fixed a bug in `plotDensityThreshold` and `plotGmmThreshold` wherein the
  `breaks` argument was ignored when specifying `xmax` and/or `xmin`.

Selection Analysis:

+ Fixed a plotting bug in `plotBaselineDensity` arising when the `groupColumn` 
  and `idColumn` arguments were set to the same column.
+ Added the `sizeElement` argument to `plotBaselineDensity` to control 
  line size
+ Renamed the `field_name` argument to `field` in `editBaseline`.


Version 0.1.9: March 30, 2018
-------------------------------------------------------------------------------

Selection Analysis:

+ Fixed a bug in `plotBaselineDensity` which caused an empty plot to be
  generated if there was only a single value in the `idColumn`.
+ Fixed a bug in `calcBaseline` which caused a crash in `summarizeBaseline` 
  and `groupBaseline` when input `baseline` is based on only 1 sequence 
  (i.e. when `nrow(baseline@db)` is 1).
+ Set default `plot` call on a `Baseline` object to `plotBaselineDensity`.
+ Removed `getBaselineStats` function.
+ Added a `summary` method for `Baseline` objects that calls 
  `summarizeBaseline` and returns a data.frame.

Mutation Profiling:

+ Fixed a bug in `shmulateSeq` which caused a crash when the input 
  sequence contains gaps (`.`).
+ Renamed the argument `mutations` in `shmulateSeq` to `numMutations`.
+ Improved help documentation for `shmulateSeq` and `shmulateTree`.
+ Added vignette for simulating mutated sequences.
+ `calcExpectedMutations` will now treat non-ACTG characters as Ns rather
  than produce an error.
+ Added two new `RegionDefinition` objects for the full V segment as
  single region (`IMGT_V_BY_SEGMENTS`) and the V segment with each
  codon as a separate region (`IMGT_V_BY_CODONS`).

Targeting Models:

+ Added the `calculateMutability` function which computes the aggregate 
  mutability for sequences.
+ Fixed a bug that caused `createSubstitutionMatrix` to fail for data 
  containing only a single V family.
+ Changed the default model to silent mutations only (`model="S"`) in 
  `createSubstitutionMatrix`, `createSubstitutionMatrix` and 
  `createTargetingModel`
+ Set default `plot` call on a `TargetingModel` object to `plotMutability`.


Version 0.1.8: June 30, 2017
-------------------------------------------------------------------------------

General:

+ Corrected several functions so that they accept both tibbles and data.frames.

Distance Calculation:

+ Adding new fitting procedures to the `"gmm"` method of `findThreshold()` 
  that allows users to choose a mixture of two univariate density distribution 
  functions among four available combinations: `"norm-norm"`, `"norm-gamma"`,  
  `"gamma-norm"`, or `"gamma-gamma"`.
+ Added the ability to choose the threshold selection criteria in the `"gmm"`
  method of `findThreshold()` from the best average sensitivity and specificity, 
  the curve intersection or user defined sensitivity or specificity.
+ Renamed the `cutEdge` argument of `findThreshold()` to `edge`.

Mutation Profiling:

+ Redesigned `collapseClones()`, adding various deterministic and stochastic
  methods to obtain effective clonal sequences, support for including ambiguous 
  IUPAC characters in output, as well as extensive documentation. Removed 
  `calcClonalConsensus()` from exported functions.
+ Added support for including ambiguous IUPAC characters in input for 
  `observedMutations()` and `calcObservedMutations()`.
+ Fixed a minor bug in calculating the denominator for mutation frequency in 
  `calcObservedMutations()` for sequences with non-triplet overhang at the tail.
+ Renamed column names of observed mutations (previously `OBSERVED`) and 
  expected mutations (previously `EXPECTED`) returned by `observedMutations()`
  and `expectedMutations()` to `MU_COUNT` and `MU_EXPECTED` respectively.

Selection Analysis:

+ `calcBaseline()` no longer calls `collapseClones()` automatically if a `CLONE`
  column is present. As indicated by the documentation for `calcBaseline()` 
  users are advised to obtain effective clonal sequences (for example, calling
  `collapseClones()`) before running `calcBaseline()`.
+ Updated vignette to reflect changes in `calcBaseline()`.


Version 0.1.7: May 14, 2017
-------------------------------------------------------------------------------

Mutation Profiling:

+ Fixed a bug in `collapseClones()` that prevented it from running when `nproc`
  is greater than 1.


Version 0.1.6: May 12, 2017
-------------------------------------------------------------------------------

General:

+ Internal changes for compatibility with dplyr v0.6.0.
+ Removed data.table dependency.

Mutation Profiling:

+ Fixed a bug in `collapseClones()` that resulted in erroneous `CLONAL_SEQUENCE`
  and `CLONAL_GERMLINE` being returned.
+ Added a vignette describing basic mutational analysis.
+ Remove console notification that `observedMutations` was running.


Version 0.1.5: March 23, 2017
-------------------------------------------------------------------------------

General:

+ License changed to Creative Commons Attribution-ShareAlike 4.0 International
  (CC BY-SA 4.0).

Selection Analysis:

+ Fixed a bug in p-value calculation in `summarizeBaseline()`. The returned 
  p-value can now be either positive or negative. Its magnitude (without the 
  sign) should be interpreted as per normal. Its sign indicates the direction 
  of the seLicense chalection detected. A positive p-value indicates positive selection, 
  whereas a negative p-value indicates negative selection.
+ Added `editBaseline()` to exported functions, and a corresponding section 
  in the vignette. 
+ Fixed a bug in counting the total number of observed mutations when performing
  a local test for codon-by-codon selection analysis in `calcBaseline()`.

Targeting Models:

+ Added `numMutationsOnly` argument to `createSubstitutionMatrix()`, enabling
  parameter tuning for `minNumMutations`.  
+ Added functions `minNumMutationsTune()` and `minNumSeqMutationsTune()` to 
  tune for parameters `minNumMutations` and `minNumSeqMutations` in functions 
  `createSubstitutionMatrix()` and `createMutabilityMatrix()` respectively. 
  Also added function `plotTune()` which helps visualize parameter tuning using
  the abovementioned two new functions. 
+ Added human kappa and lambda light chain, silent, 5-mer, functional targeting
  model (`HKL_S5F`).
+ Renamed `HS5FModel` as `HH_S5F`, `MRS5NFModel` as `MK_RS5NF`, and `U5NModel` 
  as `U5N`.
+ Added human heavy chain, silent, 1-mer, functional substitution model (`HH_S1F`),
  human kappa and lambda light chain, silent, 1-mer, functional substitution model 
  (`HKL_S1F`), and mouse kappa light chain, replacement and silent, 1-mer, 
  non-functional substitution model (`MK_RS1NF`).
+ Added `makeDegenerate5merSub` and `makeDegenerate5merMut` which make degenerate
  5-mer substitution and mutability models respectively based on the 1-mer models. 
  Also added `makeAverage1merSub` and `makeAverage1merMut` which make 1-mer 
  substitution and mutability models respectively by averaging over the 5-mer models. 

Mutation Profiling:

+ Added `returnRaw` argument to `calcObservedMutations()`, which if true returns 
  the positions of point mutations and their corresponding mutation types, as 
  opposed to counts of mutations (hence "raw"). 
+ Added new functions `slideWindowSeq()` and `slideWindowDb()` which implement 
  a sliding window approach towards filtering a single sequence or sequences in
  a data.frame which contain(s) equal to or more than a given number of mutations 
  in a given number of consecutive nucleotides.
+ Added new function `slideWindowTune()` which allows for parameter tuning for
  using `slideWindowSeq()` and `slideWindowDb()`.
+ Added new function `slideWindowTunePlot()` which visualizes parameter tuning 
  by `slideWindowTune()`.
  
Distance Calculation:

+ Fixed a bug in `distToNearest` wherein `normalize="length"` for 5-mer models
  was resulting in distances normalized by junction length squared instead of
  raw junction length.
+ Fixed a bug in `distToNearest` wherein `symmetry="min"` was calculating the 
  minimum of the total distance between two sequences instead of the minimum
  distance at each mutated position.
+ Added `findThreshold` function to infer clonal distance threshold from 
  nearest neighbor distances returned by `distToNearest`.
+ Renamed the `length` option for the `normalize` argument of `distToNearest`
  to `len` so it matches Change-O.
+ Deprecated the `HS1FDistance` and `M1NDistance` distance models, which have 
  been renamed to `hs1f_compat` and `m1n_compat` in the `model` argument of
  `distToNearest`. These deprecated models should be used for compatibility 
  with DefineClones in Change-O v0.3.3. These models have been replaced by 
  replaced by `hh_s1f` and `mk_rs1nf`, which are supported by Change-O v0.3.4. 
+ Renamed the `hs5f` model in `distToNearest` to `hh_s5f`.
+ Added support for `MK_RS5NF` models to `distToNearest`.
+ Updated `calcTargetingDistance()` to enable calculation of a symmetric distance
  matrix given a 1-mer substitution matrix normalized by row, such as `HH_S1F`.
+ Added a Gaussian mixture model (GMM) approach for threshold determination to 
  `findThreshold`. The previous smoothed density method is available via the 
  `method="density"` argument and the new GMM method is available via
  `method="gmm"`.
+ Added the functions `plotGmmThreshold` and `plotDensityThreshold` to plot 
  the threshold detection results from `findThreshold` for the `"gmm"` and
  `"density"` methods, respectively.

Region Definition:

+ Deleted `IMGT_V_NO_CDR3` and `IMGT_V_BY_REGIONS_NO_CDR3`. Updated `IMGT_V` 
  and `IMGT_V_BY_REGIONS` so that neither includes CDR3 now.


Version 0.1.4:  August 5, 2016
-------------------------------------------------------------------------------

Selection Analysis:

+ Fixed a bug in calcBaseline wherein the germline column was incorrected 
  hardcoded, leading to erroneous mutation counts for some clonal consensus 
  sequences.

Targeting Models:

+ Added `numSeqMutationsOnly` argument to `createMutabilityMatrix()`, enabling
  parameter tuning for `minNumSeqMutations`.
  

Version 0.1.3:  July 31, 2016
-------------------------------------------------------------------------------

General:

+ Added ape and igraph dependency
+ Removed the `InfluenzaDb` data object, in favor of the updated `ExampleDb`
  provided in alakazam 0.2.4.
+ Added conversion of sequence to uppercase for several functions to support
  data that was not generated via Change-O.

Distance Calculation:

+ Added the `cross` argument to `distToNearest()` which allows restriction of 
  distances to only distances across samples (ie, excludes within-sample 
  distances).
+ Added `mst` flag to `distToNearest()`, which will return all distances to 
  neighboring nodes in a minimum spanning tree.
+ Updated single nucleotide distance models to use the new C++ distance
  methods in alakazam 0.2.4 for better performance.
+ Fixed a bug leading to failed distance calculations for the `aa` model 
  of `distToNearest()`.
+ Fixed a bug wherein gap characters where being translated into Ns (Asn) 
  rather than Xs within the `aa` model of `distToNearest()`.

Mutation Profiling:

+ Added the `MutationDefinition` `VOLUME_MUTATIONS`.
+ Added the functions `shmulateSeq()` and `shmulateTree()` to simulate
  mutations on sequences and lineage trees, respectively, using a 5-mer
  targeting model.
+ Renamed `collapseByClone`, `calcDbExpectedMutations` and 
  `calcDbObservedMutations` to `collapseClones`, `expectedMutations`,
  and `observedMutations`, respectively.
  
Selection Analysis:

+ Fixed a bug wherein passing a `Baseline` object through `groupBaseline()`
  multiple times resulted in incorrect normalization.
+ Added `title` options to `plotBaselineSummary()` and `plotBaselineDensity()`.
+ Added more control over colors and group ordering to `plotBaselineSummary()` 
  and `plotBaselineDensity()`.
+ Added the `testBaseline()` function to test the significance of 
  differences between two selection distributions.
+ Improved selection analysis vignette. 


Version 0.1.2:  February 20, 2016
-------------------------------------------------------------------------------

General:

+ Renamed package from shm to shazam.
+ Internal changes to conform to CRAN policies.
+ Compressed and moved example database to the data object `InfluenzaDb`.
+ Fixed several bugs where functions would not work properly when passed 
  a `dplyr::tbl_df` object instead of a `data.frame`.
+ Changed R dependency to R >= 3.1.2.
+ Added stringi dependency.

Distance Calculation:

+ Fixed a bug wherein `distToNearest()` did not return the nearest neighbor 
  with a non-zero distance.

Targeting Models:

+ Performance improvements to `createSubstitutionMatrix()`,  
  `createMutabilityMatrix()`, and `plotMutability()`.
+ Modified color scheme in `plotMutability()`.
+ Fixed errors in the targeting models vignette.

Mutation Profiling:

+ Added the `MutationDefinition` objects `MUTATIONS_CHARGE`, 
  `MUTATIONS_HYDROPATHY`, `MUTATIONS_POLARITY` providing alternate approaches
  to defining replacement and silent annotations to mutations when calling
  `calcDBObservedMutations()` and `calcDBExpectedMutations()`.
+ Fixed a few bugs where column names, region definitions or mutation models
  were not being recognized properly when non-default values were used.
+ Made the behavior of `regionDefinition=NULL` consistent for all mutation
  profiling functions. Now the entire sequence is used as the region and
  calculations are made accordingly.
+ `calcDBObservedMutations()` returns R and S mutations also 
  when `regionDefinition=NULL`. Older versions reported the sum of R and S 
  mutations. The function will add the columns `OBSERVED_SEQ_R` and
  `OBSERVED_SEQ_S` when `frequency=FALSE`, and `MU_FREQ_SEQ_R` and 
  `MU_FREQ_SEQ_R` when `frequency=TRUE`.
    

Version 0.1.1:  December 18, 2015
-------------------------------------------------------------------------------

General:

+ Swapped dependency on doSNOW for doParallel.
+ Swapped dependency on plyr for dplyr.
+ Swapped dependency on reshape2 for tidyr.
+ Documentation clean up.

Distance Calculation:

+ Changed underlying method of calcTargetingDistance to be negative log10 of
  the probability that is then centered at one by dividing by the mean 
  distance.
+ Added `symmetry` parameter to distToNearest to change behavior of how 
  asymmetric distances (A->B != B->A) are combined to get distance 
  between A and B. 
+ Updated error handling in distToNearest to issue warning when unrecognized
  character is in the sequence and return an NA.
+ Fixed bug in 'aa' model in distToNearest that was calculating distance
  incorrectly when normalizing by length.
+ Changed behavior to return nearest nonzero distance neighbor.

Mutation Profiling:

+ Renamed calcDBClonalConsensus to collapseByClone
  Also, renamed argument collapseByClone to expandedDb.
+ Fixed a (major) bug in calcExpectedMutations. Previously, the targeting calculation
  was incorrect and resulted in incorrect expected mutation frequencies. Note, that this
  also resulted in incorrect BASELINe Selection (Sigma) values.
+ Changed denominator in calcObservedMutations to be based on informative 
  (unambiguous) positions only.
+ Added nonTerminalOnly parameter to calcDBClonalConsensus indicating whether
  to consider mutations at leaves or not (defaults to false).
  
Selection Analysis:

+ Updated groupBaseline. Now when regrouping a Baseline object (i.e. grouping previously
  grouped PDFs) weighted convolution is performed. 
+ Added "imbalance" test statistic to the Baseline selection calculation.
+ Extended the Baseline Object to include binomK, binomN and binomP
  Similar to numbOfSeqs, each of these are a matrix. They contain binomial inputs for 
  each sequence and region. 
  
Targeting Models:

+ Added `minNumMutations` parameter to createSubstitutionMatrix. This is the 
  minimum number of observed 5-mers required for the substituion model. 
  The substitution rate of 5-mers with fewer number of observed mutations
  will be inferred from other 5-mers. 
+ Added `minNumSeqMutations` parameter to createMutabilityMatrix. This is the 
  minimum number of mutations required in sequences containing the 5-mers of 
  interest. The mutability of 5-mers with fewer number of observed mutations 
  in the sequences will be inferred. 
+ Added `returnModel` parameter to createSubstitutionMatrix. This gives user 
  the option to return 1-mer or 5-mer model.
+ Added `returnSource` parameter to createMutabilityMatrix. If TRUE, the 
  code will return a data frame indicating whether each 5-mer mutability is 
  observed or inferred. 
+ In createSubstitutionMatrix and createMutabilityMatrix, fixed a bug when
  multipleMutation is set to "ignore".
+ Changed inference procedure for the 5-mer substitution model.
+ Added inference procedure for 5-mers without enough observed mutations
  in the mutability model.
+ Fixed a bug in background 5-mer count for the RS model.
+ Fixed a bug in IMGT gap handling in createMutabilityMatrix.
+ Fixed a bug that occurs when sequences are in lower cases.


Version 0.1.0:  June 18, 2015
-------------------------------------------------------------------------------

Initial public release.

General:

+ Restructured the S4 class documentation.
+ Fixed bug wherein example `Influenza.tab` file did not load on Mac OS X.
+ Added citations for `citation("shazam")` command.
+ Added dependency on data.table >= 1.9.4 to fix bug that occured with 
  earlier versions of data.table.

Distance Calculation:

+ Added a human 1-mer substitution matrix, `HS1FDistance`, based on the
  Yaari et al, 2013 data.
+ Set the `hs1f` as the default distance model for `distToNearest()`.
+ Added conversion of sequences to uppercase in `distToNearest()`.
+ Fixed a bug wherein unrecongized (including lowercase) characters would
  lead to silenting returning a distance of 0 to the neared neighbor. 
  Unrecognized characters will now raise an error.

Mutation Profiling:

+ Fixed bug in `calcDBClonalConsensus()` so that the function now works 
  correctly when called with the argument `collapseByClone=FALSE`.
+ Added the `frequency` argument to `calcObservedMutations()` and
  `calcDBObservedMutations()`, which enables return of mutation frequencies
  rather the default of mutation counts.
  
Targeting Models:

+ Removed `M3NModel` and all options for using said model.
+ Fixed bug in `createSubstitutionMatrix()` and `createMutabilityMatrix()` 
  where IMGT gaps were not being handled.


Version 0.1.0.beta-2015-05-30:  May 30, 2015
-------------------------------------------------------------------------------

General:

+ Added more error checking.

Targeting Models:

+ Updated the targeting model workflow to include a clonal consensus step.


Version 0.1.0.beta-2015-05-11:  May 11, 2015
-------------------------------------------------------------------------------

Targeting Models:

+ Added the `U5NModel`, which is a uniform 5-mer model.
+ Improvements to `plotMutability()` output.


Version 0.1.0.beta-2015-05-05:  May 05, 2015
-------------------------------------------------------------------------------

Prerelease for review.
