• The restriction map utility was fixed.  It was broken by the relocation of the BioEdit.ini file to the program install directory.
• An option was put into the preferences to allow temporary redirecting of file paths for blast database creation and search execution to the root directory.  The reason for this is that if the name of the database directory (when doing a search) or source directory for a fasta file (when converting to a blast database) is too long, it can overload the maximum command line length for running blastall.exe or formatdb.exe (the NCBI command-line programs used for blast utilities).

• Moved BioEdit.ini to the program current run directory.  Hopefully this will help on computers without write access to the system folder.

• Updated NCBI sequence retrieval to deal with recent changes at NCBI that broke the sequence retrieval functions in the previous version.
• Note:  (not a change, per se):  Scoring in pairwise alignment functions does not agree with the example in the help document.  This will be investigated if/when I have time.  I had considered removing the functions, but decided no to on the grounds that they generally work OK for quick manipulations and can be useful as a time-saving utility.  They should not, however, be used as a teaching tool.

• Changing proxy setting for sequence retrieval from GenBank had no affect because the routine was looking in the wrong directory for the BioEdit.ini file.

• Bug in sequence retrieval from GenBank fixed that caused retrievals to come back saying " ... format unrecognized".

• A memory bug in RNA covariation routine was fixed.

• The blast programs blastall and formatdb were modified to allow passing parameters in a file as well as on the command line to get around the Windows xommand line length limit.
• blastall and formatdb were modified to allow passing a darabase name with spaces (original verion tries to parse the name into multiple file names).
• When launching an alignment file from the Windows Explorer, BioEdit now tries to open the file in an existing BioEdit instance if there is one open, rather than opening a new one.
• Updated installer will hopefully take care of the trouble some people have been having installing BioEdit.

• The optimal pairwise alignment routine was inadvertently overwritten with a test version that was only functional on nucleic acid sequences.  This caused pairwise alignment on amino acid sequences to fail.  The original alignment method was put back.

• Documentation (online help file) was updated for the first time since version 5.0.6.  However, my help compiler has a mild Turet's syndrome and sporadically tosses numbers in here and there, listing sentences by number that did not occur in lists in the original document (will have to be fixed later).
• Automatic links to NCBI BLAST via the World Wide Web were added back with current NCBI pages with editable addresses.
• Error on doing local blast searches when swap directory contained spaces fixed.  However, BLAST won't work if entire command line is too long for Windows, so keeping the BioEdi t swap directory in a path name as short as possible (e.g. C:\BioEdit\Temp) is a good idea.
• Some context-sensitive help added (not complete).
• Fixed bug in graphic view that caused Error when view is plotted in dot conservation mode and the "reference" sequence is shorter than one of the alignment sequences.
• Fixed a bug in floating point conversion with non-English regional settings (when a ',' is used as decimal separator) that would cause an error when trying to translate nucleotide sequences into protein (bug manifested when reading in the "codon.tab" file and converting frequency numbers -- the regional settings were not being detected properly).
• Added support for mouse wheel in Alignment document window.  Clicking the mouse wheel button toggles between vertical and horizontal scroll function.
• Fixed bug in right-click-based gap deletion in grouped sequences with group-locked alignment status (gaps were being deleted only for edited sequence and no entire locked group).
• A couple of other bugs relating to adding or deleting gaps around a residue with the right mouse button in a sequence which is a member of an alignment-locked grouped were fixed.  Behavior was updated to only operate upon sequences that are not grouped together in an alignment-locked group with the sequence in question.
• Fixed bug in clustal auto-link that caused VERSION field to be lost in aligned sequences.

• Removed automatic taxonomy mapping support -- its undocumented and caused confusion.
• Removed primer pair/oligo mapping and Tm calculation -- undocumented and caused confusion.
• Removed query functions for sequence features -- again, undocumented and caused confusion.

• Removed "Auto-update View Options" because it causes long delays in Win2000 and XP.
• Fixed a bug in Graphic View new to v6.0.5 causing access violation if View Features mode is on in document window.

• Some memory troubles with grouped sequences fixed.  Using sequence groups is now more stable.
• Access violations when deleting sequences in dot conservation mode or vertically scrolling very long alignments in dot conservation mode fixed.
• Retrieve sequences directly from GenBank over the WWW.
• Automatically retrieve GenBank info from GenBank for existing sequences for Genbank-fasta formatted titles (eg. gi|16082679|ref|NC_003132.1|).
• Automatically retrieve Pubmed references for GenBank sequences.
• Multiple levels of undo (up to 30).
• Restriction on number of sequences removed.  All memory allocation for sequences was made dynamic.
• Paste over sequence blocks to quickly create subalignments based upon a region of a larger alignment or produce alignment concatenations. 
• Paste over titles, and paste onto (concatenate to) titles.
• Copy sequence titles added in a couple of variations.
• Copy nucleic acid sequence blocks in reverse complemented orientation
• Copy sequences in a tab-delimited format (for pasting into a spreadsheet)
• Find/replace function for sequence information
• Flexible find/replace in titles with indexed wildcards
• Filter leading and trailing characters off of sequence titles.
• Find titles equal to, beginning with, or containing lists of strings.
• Unique based upon sequences or title with a two-step sort + select & delete process to remove redundant sequences or titles
• Query sequences by data by TITLE, LOCUS, DEFINITION, ACCESSION, VERSION / GI, PID (or SID), DBSOURCE, KEYWORDS, REFERENCES, FEATURES, COMMENT, and/or Phylogeny.
• Invert selection of sequences or residues
• Edit information for multiple sequences at once with Sequence-->Edit all selected.
• Extract subsequences (including orientation for DNA) from lists of coordinates (with choice of alignment-gapped or true positions) 
• Query and extract annotated sequence features.
• Map true positions from lists of alignment positions.
• Add tabulated taxonomy information to sequences.
• Several variable ways of renaming titles in batch mode (Sequence-->Rename-->...)
• Several ways to filter out sequences based upon inclusion/exclusion of specific characters, length, or number of leading, trailing, or total gaps.
• Sort by phylogeny
• Invert current sequence order
• Map oligos and primer pairs to alignments based upon mismatch threshold
• Calculate DNA oligo Tm's with mismatches based upon thermodynamic parameters from John SantaLucia's lab.
• Calculate Tm's for oligos and compare them to same region of other sequences from alignment window using right mouse button clicks.
• Several operations on local sequence region selection with right mouse button click.
• Speed enhanced on pairwise alignment of large similar sequences
• Align sequences to an existing alignemnt by pairwise alignment to phylogenetic near neighbor in existing alignment.
• Choose individual restriction enzymes when creating a restriction map.
• Easily flush an alignment out with gaps to produce a rectangular matrix

• Made a minor adjustment to preferences for characters to be treated as residues -- There's an option to either include them as positions or ignore them completely for similarity/ID shading.
• Fixed a bug in pasting into the single sequence editor window.

• Protein alignments in new installations may have shading problems because when the option to explicitly specify all characters to be considered valid for calculations (including ID/similarity shading), 'N' was accidentally missed for amino acids.  Several installations  probably have gone out with 'N' missing from the list of amino acids.  This can cause protein alignments to have similarity/identity shading errors.  'N' has been put back into the default.
• Access violations could occurr when typing in an RNA structure mask while in RNA base pair coloring mode, and when there is a non-symmetric number of openeing vs. closing brackets.  This has been fixed.

• Added base pair mask support for RNA alignments.
• Added base-pair coloring for RNA alignments with user-defined color scheme.
• Fixed bug in creating local Blast databases from within a sequence document.

• Added support for phylogenetic trees without distance information.
• Added save function for phylogenetic trees.
• Added linking of phylogentic trees to an alignment.
• Multiple trees may be imported from one or several files.
• Incorporated phylogentic trees are saved with alignment in BioEdit alignment format.
• Added option to view trees with or without distance information.
• Updated sequence label editing to allow spaces in comments.

• Added node flipping to phylogenetic tree viewer.
• Added printing to phylogenetic tree viewer.
• Fixed bug in the "append alignments" (the first alignment was appended to itself) -- bugged version was only out for one day.

• Fixed some issues with accessory app linking (problems keep creeping up related to the change made in version 5.0.0 to specify a swap folder for temp files).
• Added the option to merge alignments by appending one alignment to the end of another.

Added a ruimentary tree viewer (VERY unfinished -- only reads phylip trees, only in "phylogram" view, no distance ruler yet, no print, save or manipulate yet) -- The reason for having an internal tree viewer is to in the future allow flipping of nodes and resaving the tree for use in nicer tree viewing programs like TreeView that allow better formatting, but don't have manipulation options.  Also, it would be nice in the future to directly link phylogenetic tree views to alignment files for quick phylogeny reference.

• Fixed a bug (hopefully) that caused accessory apps to not run correctly (bad command or filename error).
• Added column anchoring to protect areas that are already aligned.
• Updated translation toggling so that gaps that are expanded back from a single gap (when toggling from a protein view to a nucleotide view) are always "locked" (to avoid problems with inadvertently crunching off-screen gaps that spuriously toggled back as "unlocked" when aligning by hand).
• Fixed a bug that caused RNA covariation, potential pairings, or mutual information analyses to crash when "mask numbering" was chosen but there was no numbering mask specified.
• Fixed newly introduced bug the caused MI Examiner to crash when no masks are specified.

• Updated Mutual Information Examiner to handle lists of positions.
• Added several options to Mutual Information preferences to allow variable display of list information in MI Examiner.
• Added option to export and import color table files.
• Fixed a bug that caused color table to lock sometimes.
• Added option to toggle translations using the current selected residue as a reference frame.
• Fixed a bug that caused document to appear hung when sort by base frequency was chosen without a selected column.
• Added ability to sort by selected range of residues.
• No longer append sequence lengths to titles when saving Fasta files.
• Added preference (on "General" tab) to require verification for revert to saved function.
• Fixed problem with creating Local Blast databases which would occur on machines with no NCBI tools installed. 
• Accessory apps and Blast Internet client are now launched through an auto-generated batch file.

• Added the option to specify user-defined temp (swap) directory for all temporary files and user-defined BLAST database directory so that BioEdit may be used from a drive space that does not allow writing (actually added to v5.0.0 a few days before 5.0.1 came out).
• Fixed some bugs associated with running accessory apps from version 5.0.0 after the temp directory option was added. 

• Added options to specify which characters in nucleic acid and amino acid sequences are considered to be valid for calculations.
• Added options for sorting sequences by title, LOCUS, DEFINITION, ACCESSION, PID/NID, REFERENCES, COMMENTS and residue frequency in a selected column.
• Added options to annotate sequences with graphical features, using the standard GenBank FEATURES tags as the standard for keeping track of annotation "type", but allowing full user control over feature names,  descriptions, colors, shapes and positions.
• Added function to automatically annotate graphical features using existing GenBank FEATURES field
• Added options for grouping sequences into groups or families, with user-defined coloring of grouped titles and the option to lock the alignment of grouped sequences to allow synchronized hand alignment  adjustments between grouped and locked sequences.
• Added option to lock individual sequences to prevent accidental edits.
• Updated the BioEdit file format to save graphical annotations, sequence group information, locked sequence information and positional flags.
• Added function to update previously saved BioEdit plasmid maps with a new restriction enzyme file when the ReBase file is changed (changing the enzyme.tab file can cause mis-indexing of restriction enzyme sites in existing plasmid files).
• Updated shaded graphic view to correctly do conservation (dot) view when that view mode is selected in the alignment window (no to create a new dot-plotted alignment and any sequence can be used as the reference rather than just the top sequence).
• Added a "Overwrite" and "Insert" modes to both on-screen and single-sequence editor sequence editing.
• Updated local BLAST interface to feed multiple sequence automatically for a batch job, and to allow specification of a permanent file output and the option to open output automatically in the BioEdit text editor or not. 
• Modified some menus (Edit and Sequence menus, mainly).  The same options (and more) are still there, but submenus having been created to group certain related functions including: gap-realted functions, pairwise alignment functions, simple manipulations (reverse, uppercase, lowercase, remove numbers), and search functions.
• The "No BLAST" version (BioEdit without local BLAST packaged) was done away with -- it's too much of  pain to duplicate everything but one extra function and make a whole independent installation when relatively few people download that one anyway).
• At the last minute -- added an option to verbally read back sequences (protein, nucleic acid, or anything else) to verify hand-typed sequence entries.
• The docuentation was updated 12/18/2000.

Bug fixes/changes since v4.8.9:

• Fixed the (re-introduced) bug that caused floating point number formatting error when translating nucleic acid sequences on non-US regional settings machines

Fixed a couple of bugs that affected reading in of sample name and version on ABI 310 files

Bug fixes/changes since v4.8.7:

• Removed the internal web browser
• Fixed a bug in codon frequency reporting (nucleotide translations) that caused floating point numbers to sometimes get jumbled up in the output

Added a conservation plot toggle to the main alignment window with the option to choose the character to draw for a "conserved residue" (the "reference" sequence defaults to the first sequence in an alignment -- RIGHT-CLICK the mouse over any sequence to change it to the current reference sequence for this view option)
• Fixed a minor bug in setting of custom menu shortcuts for alignment documents.  The "Import from clipboard" should now work with a user-defined menu shortcut.

• Added optimal pairwise alignment routine with a summary of percent identity and similarity (multiple choices for scoring matrix for amino acid alignment, user-defined gap initiate, gap extend and nucleotide match parameters, and option for global alignment or alignment allowing ends to slide over each other).
• Added routine to create an alignment that plots all residues that are identical to the top sequence in an alignment as a dot.
• Added a cheap version of a dot plotter for plotting matrix similarity between two sequences -- total sequence length product cannot exceed 2000 x 2000, however, so it's not useful for genome comparisons or even moderately large sequences.
• Added option to calculate the similarity and/or identity between two sequences as they are aligned.

• 3/10/2000 -- added NCBI blastcl3 to distribution and added a more versatile linking interface for the BLAST client -- the old BLAST client 2 has apparently been disabled
• 3/10/2000 -- Added block convention to user-defined motif search.  [] brackets indicate ambiguous residues and {} brackets indicate exclusions (eg [LIV] will accept 'L', 'I' or 'V', whereas {LIV} will accept anything BUT 'L', 'I' or 'V'.
• 3/10/2000 -- Fixed bug that caused an eror and a blank doc to be opened when the alignment control bar was hidden
• 3/10/2000 -- Fixed a couple of bugs related to reading and writing of GenBank files (lines beginning with numbers were truncated and manually updating fields sometimes resulted in misformatting) 
• Added an alignment merge funcion which merges two alignments based upon a standard common to both alignments 
• Added batch export of ABI raw trace data.
• Fixed the recently introduced disabling of the ABI/SCF trace print option
• Fixed metafile copy and print of reverse-complemented traces
• Improved default scaling of SCF traces for printing and metafile copy
• Fixed bug in graphic view which could affect first time use of the graphic view when used with non-US Windows regional settings 

• 1/28/2000 -- Fixed bug that came out when creating a mask (must have been introduced in version 4.7.8).  This bug caused two masks to be formed and sequence memory for the first two sequences to get cross-linked. (caused by accidentally re-assigning a memory pointer rather than an entire data structure).
• 1/27/2000 -- Fixed a bug that was introduced with the very last bug fix concerning ClustalW 1.4 to 1.8 upgrading.  With ClustalW 1.4 (the version distributed with BioEdit) the sequence names would get mangled and GenBank information was not being copied into the new alignment.  This should be fixed in version 4.8.5 installations downloaded after 1/27/2000
• Fixed potential bug that comes out if you replace the clustalw 1.4 (the version distributed with BioEdit) with clustalw 1.8 in the apps folder -- clustalw 1.8 will rearrange the order of the input sequences, causing sequences and titles to become scrambled in the new alignment -- this has been fixed.
• Added raw data view and analyzed and raw data export from .abi trace files.
• Added option to change starting point of ruler bar in alignment window.

• 1/4/2000 -- Fixed bug in read-in filter for Phlyip 3.2 (non-interleaved) files that cauesed DNA/RNA alignments to be detected as protein
• 2/20/1999 -- Added helical wheel diagrams for proteins.  Select a protein or portion of a protein and choose Sequence->Protein->Helical Wheel Diagram
• Fixed bug in accessory app launching that causes spaces to be lost in command prefixes for inputs and checkboxes
• Added option to accessory app launching to auto-feed sequences in separate files (eg, for Lalign from the Fasta package)

• 12/13/1999 -- Fixed bug in hydrophobic moment profiles -- had an exponent missing in Fourier equation 
• 12/13/1999 -- Added hydrophobic moment matrix plots (0-180 degrees)
• 12/13/1999 -- fixed a couple of bugs in trace viewer that caused problems with non-U.S. regional settings
• 12/10/1999 -- Added support for SCF version 2.00 files

• Added options to accessory application interface:
1. Bypass interface when running an accessory
2. Link output(s) of one accessory to another/other accessory(s)
3. Create accessory app links that are only called by other accessory links and do not show up on accessory app menu
4. Automatically truncate titles to 10 characters for programs that don't accept long names and/or change spaces to '_'
5. Rename redundant sequence names and generate a report file specifying title changes

• 12/2/1999 -- Fixed a bug in accessory application launching that could cause a memory error when running an app from a window that is not a sequence alignment document
• 12/1/1999 -- Fixed on-screen title editing so that double-clicking on a selected title still opens the sequence editing box and overrides title editing
• 12/1/1999 -- Added option to disable on-screen editing
• 12/1/1999 -- Fixed bug in consensus sequence generation. A consensus generated from less than all of the sequences in an alignment was using frequencies calculated using the total number of sequences rather than the selected number

12/1/1999 -- Fixed bug that caused an access violation when re-activating a document that had sequences deleted (introduced with version 4.7.8)
• Fixed a very bad bug that was introduced in version 4.7.8.  Pasting sequences within an alignment document caused sequence structures to become cross-linked due to a duplicated pointer.  This would lead to memory access violations and possible loss of data.  This has been fixed.

• Added support for SCF sequence trace files
• Added horizontal and vertical zoom controls to sequence trace form
• Added crosshairs with trace position reporting in trace form
• Added batch conversion of ABI files to SCF format
• Traces draw faster on the screen
• Fixed another bug in on-screen sequence title editing (when vertical bar was scrolled, it was causing trouble with the identity of the edited title)

• Fixed bug in local BLAST linking that caused failure when operating from a directory with a space in its name and using a mtrix other than Blosum62
• Fixed a similar bug in linking to ReadSeq for importing and exporting of extra file formats
• Added "Import from Clipboard" and "New from Clipboard" functions unde the file menu -- Clipboard contents are treated exactly like a file an automatic linking to ReadSeq for importing formats that BioEdit does not internally read is maintained
• Added function for inserting multiple gaps at selected residue positions or at specified position in selected sequences
• Updated on-screen title editing -- use the arrow keys to scroll up and down when changing several titles in the same document
• Fixed a bug in plasmid drawing that caused a floating point error when adding a very short feature to a circular plasmid

• Fixed a bug that caused keystrokes to appear in sequences while in edit mode but changing sequence titles or accessing menus with alt+ keystrokes
• User-defined motif search function added for amino acid, nucleic acid, or simple text.
• Memory allocation for sequences changed to use less memory (memory was being allocated to set aside space for 20,000 sequence structures regardless of the number of sequences in a file -- now a single pointer is set aside for the max number of allowed sequences (20,000), but no memory is allocated until a sequence is created)
• Bug in ABI trace reader was fixed that caused trace / nucleotide colors to be mismatched when the file contained an order other than "GATC"

• ABI files may be edited and saved, and edited sequence may be reverted to the original, non-editable version.  The edited sequence is opened as a sequence/alignment doc upon opening an ABI file.
• Extended capabilities of restriction mapping module.  Long sequences may be mapped (tested up to 1.75 Mb on machine with 128 Mb RAM).  My mapping procedure is pretty slow, but 500,000 bp runs in ~2 minutes on a 366 MHz Celeron).  Progress indicators added for long sequences.
• Added local BLAST interface to main program interface (rather than just in sequence/alignment docs)
• The paste in the sequence edit box that caused it to go very slow with long sequences has been fixed (>500,000 residue pasting is no longer a problem).

• Fixed link to readseq for import/export of extra formats that made it fail with long file names
• Added read-in filter for GCG format
• a couple of other minor bug fixes

• Fixed a few leftover bugs in the graphic shaded views (mostly spacing)
• user control over vertical spacing of sequences
• Added view of similarity scoring matrix files from doc windows
• Edit titles on screen (highlight a title, then click it again)
• Fixed bug in local blastp -- matrix choices other than BLOSUM62 should work now

• A rich text export was added to the shaded graphic view utility.  This uses the highlight command in the Rich Text Format specification 1.5, and is probably compatable only with relatively modern word-processors.
• Made a few changes and fixes to the shaded view. 
• Added a "find in next title" function to the main document window

• Clustal format (.aln) filter was updated so it now compatible with the sequence numbers option in ClustalX
• A "delete numbers" option was put in under the sequence menu to allow easier compatability with copying and pasting from numbered formats
• In the shaded graphic view, an option to print lines continuously (not broken by a space every ten residues) was added
• An option to place translations below nucleotide sequences in either one-letter or three-letter format was added (allows for coloring with amino acid color table colors, but no similarity shading of the amino acids in this view).

• 8/27/1999: Added option for outlines around identity and similarity shading in shaded graphic view of alignments
• 8/27/1999:  Fixed small bug in restriction maps.  If more than one enzyme cut at the very position starting a new line on the printed map, only the first enzyme would show on the map (though all would appear in the lists). 
• User options are provided for a (hopefully) more useful consensus sequence generation.
• The ABI trace viewer was updated to provide summary information and to allow copying of the trace window as a bitmap (in last version, I forgot to add that the option to copy print pages as Metfiles was also added).
• Support for reading Clustal format has been added (no save, only open).

• The graphic shaded view was improved.  It's more like a print preview.  Also, the option to add numbers to the sides of the sequences has been added
• *Another* introduced bug was fixed in the accessory applications launch interface.  This bug was preventing input and output file name command prefixes from being added to the command line (needless to say, many apps would not run).
• Font size control has been added to the single sequence editing box. 
• Accessory apps no longer need to be run from an alignment doc unless they operate upon sequence output.

• Added support for ABI chromatograms.  Display traces, import sequence, select, copy, export, reverse complement and print with professional-looking output.
• Fixed a couple of memory leaks (some sequence memory was not being released and some memory allocated during manipulation of plasmid images and matrix plot images was "leaking")
• Fixed a bug in formatting output of GenBank files containig extra field data (REFERENCES, SOURCE, etc)
• 7/20/1999:  Fixed bug in translations with codon usage that occurred when sequences had characters other than A, G, C, T or U.

• 7/6/1999 -- corrected error in molecular mass calculations for nucleic acids (there was an extra water molecule (18 Da) for every internal nucleotide)
• Corrected 'Del' key behavior in edit residues mode and in single sequence edit interface
• Added sequence number to beginning of mouse position labels
• Fixed alignment of ruler ticks for non-type-set fonts

• Fixed a bug that caused simultaneous entry of characters into mutual information examiner X or Y entry and sequence when in Edit Residues mode
• Fixed glich that caused ruler to not extend to end of window in very high screen resolutions with small font size
• Fixed problem (I think) with disappearing window controls (minimize, maximize and close controls)
• Fixed bug in accessory application interface that caused spaces between input and output file prefixes and filenames to not be added to the command line 
• Modified accessory application interface to use short path names for input files (Some programs would not run correctly from directories with spaces in them, eg Program Files)

• Scroll a full screen at a time with the PageUp/PageDown keys and with Ctrl+arrow keys -- also refined cursor movement in edit mode and keyboard-controlled scrolling
• BioEdit now remembers your last window state as the default
• Fixed a bug in the single sequence edit window -- applying twice in a row after creating a new sequence no longer causes an access violation
• Improved speed of dynamic shading of protein alignments in the edit window 

• Fixed bug in edit-window shading (maximizing window shouldn't cause a problem now).
• Added Select to End, Select to Beginning and Select Residues of  Selected Sequences functions 
• Changed open and save file dialogs to remember file extensions and last directory as defaults
• Added recent file list to the file menu
• Added function to open an edit box at the current cursor position (when in Edit Residues mode) 

• Added identity/similarity-based shading in the alignment window
• Fixed a bug in the matrix plotter which caused it to periodically crash when plotting a half matrix (above diagonal only).
• Fixed bug in N-best reporting of mutual information and N-best and P-best reports when data are organized for the whole alignment rather than by position (I forgot that those things had never been finished).

• Added information-based searching for conserved segments (may be useful for designing PCR primers or defining motifs)
• Made the sequence titles window adjustable in width
• Fixed bug in six-frame translations:  An "N" in the sequence no longer causes an amino acid to be skipped
• Added a "Minimize Alignment to Mask" function to allow trimming an alignment to positions present in a mask sequence
• Added positional numerical summary for nucleotide alignments
• Changed entropy plots to area plots that resize with the window
• Added a full-text summary of entropy (Hx) values when an entropy plot is run 
• Got rid of the "three-way information" thing (too much noise to be useful)

• The vertical split has been improved -- no longer flickers wildly when going between windows (also, no longer "left" and "right" panes -- it's just one window now).  The horizontal split view is still not-so-great.
• Added option to hide panels for controls at top (to allow for a bigger sequence editing window)
• Sped-up right-click driven insertions and deletions.  Added option to reverse mouse buttons (to allow inserting and deleting gaps with a left click)
• Fixed glich in window updating when switching between color and B&W
• Fixed glich in translations on restriction maps -- spacing was off if an "X" resulted from a codon with a non-A, C, G or U/T character.
• Added menu items for all button-driven controls
• "Lock gaps" no longer causes an error when residue selection goes beyond the end of a sequence.

• Fixed bug in residue selecting that was introduced with the sequence handling rewrite:  The location of a selected block of residues was not scrolling correctly in the horizontal direction
• Changed the way the matrix plotter draws matrices.  The speed is improved several hundred fold. 
• Added threshold control to matrix plotter.

• Fixed glich in amino acid composition reporting -- previously, non-amino acid characters were assigned a mass of 110 Da.  Now, only 'X' is assigned 110, other characters are 0 Da (not counted as amino acids).  The weight of 'B' is considered the average of 'D' and 'N', and the weight of 'Z' is the average of 'E' and 'Q'.  Also, a stop codon at the end of a sequence no longer adds 1 amino acid to the reported length of the sequence.
• A couple of changes were made to the accessory application configuration interface and the way accessory apps are run:
1. Options to include or not include the input and output files in the command line were added, as well as the option to include them at the beginning or end of the command line.
2. Changed the method of calling accessory apps:  redirection of stdin and stdout now *appears* to work correctly in all cases.  The few PHYLIP programs distributed with BioEdit now have stdin redirected so they may be run fully automated.
• Forgot to report in an earlier version: a bug in converting selected regions to lowercase was fixed (left out 'A')

• The on-line help system was updated (the printable documentation still needs updating -- also the WWW documaentation needs to be updated (don't know when that'll get done)).
• Fixed a bug in resizing split windows (introduced with version 4.5.3 -- would cause an exception when the window was increased vertically due to an oversight in creating a new graphic sequence display object).

• Sequence handling and memory allocation for sequences was re-written.  Alignments load much faster and editing of large alignments is more reasonable.  When using the new BioEdit Project file format, the prokaryotic 16S rRNA alignment (6205 sequences, 29 Mb file) opens in less than 10 sec. on a Pentium 233 MHz with 80 Mb RAM. 
• Expanded sequence limit to 20,000.
• Created a new binary file format (the BioEdit Project file) for fast Open and Save of large alignments.
• A bug in formatting when exporting an aligment as raw text was fixed (the spacing would be randomly messed up -- this bug was introduced with version 4.3.8 and was only recently discovered because this feature apparently does not get used much). 
• Two bugs in the vertical split window view were fixed: 
1. When the original window's vertical scrollbar was not at the top, the right side of the split window would start out of register with the left side.
2. The left side of the window would not scroll all the way to the end.
• A couple of changes to the sequence edit box:
1. The first digit of ruler positions >1,000,000 is no longer deleted from the ruler bar.
2. The "Delete" key now works in the edit box as well as "Backspace".
• A typo on the vertical axis of Eisenberg mean hydrophobic moment plots was fixed.
• Changes to matrix plotter:
1. Clicking on the plot when there is no 1-D line plot open no longer crashes the program
2. Highlighting of the selected matrix position on the plot has been fixed (the selected position is inverted and outlined).
3. The data summary reported for a highlighted matrix position reflects the position numbers in the matrix file rather than the absolute row or column number (x and y position numbers may be discontinuous, as when alignment numbering is used to generate the M(xy) data or when a numbering mask different from the sequence mask is used).
4. The row or column numbers shown on the 1-D matrix row/column plots reflect the position numbers in the matrix file.

A bug in reporting of the current row or column that showed up when an asymmetric section of a matrix file was plotted has been fixed (if a matrix contained more rows than columns, row numbers beyond the total number of columns would be mis-reported).
• "Flags" are now available to graphically mark any position in an alignment for keeping track of positions while when going back and forth a lot.
• The sequences have been crunched together slightly for a tighter view with more sequence data on the screen at once.
• User may enable or disable position reporting at the mouse arrow.

Bug fixes/changes since v4.5.1:

• Added option to translate selected regions of nucleic acid sequencesfor formatted translation with codon summary, with the option to display the entire nucleic acid sequence or only the translated region
• Added option for single-letter or three-letter codes for amino acids in formatted translations
• Fixed a couple of bugs related to non-U.S. versions of Windows: errors resulting from the difference between U.S. and European decimal separators (period vs comma) have been fixed in the text print, RNA anaylises outputs, the matrix plotter, and formatted translations. 
• Updated matrix plotter to provide a summary of matrix dimensions before loading up a matrix, and added the capability to plot user-defined regions of matrices.  The plotter can now handle a nearly unlimited matrix size (but can still only plot ca. 1500 x 1500 (maybe up to about 2000 x 2000) at one time.  The largest file tested was 179 Mb (5183 x 5183).
• Expanded sequence limit to 10000 (sequence size is limited only by system resources and speed). 

• Vertical split window view was added
• About 16 billion bugs were fixed in the split window view synchronization

Bug fixes/changes since v4.4.2:

• Option added to split the alignment window to simulataneously work on two different parts of the same file while keeping the two views synchronized (menu option=View->Split Window)
• ORF searching (menu option=Sequence->Nucleic Acid->Find Next ORF) -- change preferences for ORF searching under Options->Preferences->ORFs) -- user-defined starts and stops and minimum length
• New edit box window:  Edit single sequence in color with an improved sequence view including ruler bar and sequence spaced out in blocks of 10.
• Improved alignment shading utility -- shade identities and similarities using the current color table or user-defined identity and similarity font and box colors.  Display sequences in color or black and white (shaded views may also be done with sequences in color now).  Copy shaded alignment to clipboard as an enhanced metafile for direct transfer as high-quality graphic into programs such as PowerPoint (text-quality, place directly onto a slide background or template).

Bug fixes/changes since v4.4.1:

• blastx was added to the local BLAST interface
• Image Export (Bitmap or Windows Metafile) added to plasmid utility with variable output size options
• Clipboard copy as a Windows Metafile added to plasmid utility and to shaded graphic view utility

Bug fixes/changes since v4.4.0:

• Fixed "Cut" and "Copy" options for working with linked nucleotide/protein views.
• Added user control over menu shortcuts in alignment documents (to customize shortcuts, go to "Customize Menu Shortcuts" from the "View" menu)
• Added "Auto-Update View Options" item under the "View" menu -- when checked, the "Save Options as Default" item is not visible, and view options are automatically saved whenever a change is made
• Fixed redraw of ends of sequences when in a non-typeset font.

Bug fixes/changes since v4.3.10:

• Fixed bug in translating and translation toggling (no longer bombs out after several translations)
• Multi-file handling for opening and importing sequence files
• Non-typeset font handling was improved for the editing window and in graphic shaded view
• Read filters for NBRF/PIR and Phylip 4 formats were improved
• Monochrome sequence view fixed (can't remember when or how I broke it -- but it got broken).
• Three options were added for handling gaps for translating when toggling between nucleotide and protein views:
1. Gaps automatically adjusted to occur in groups of three that do not disrupt codons
2. Gaps that disrupt codons or do not occur in groups of three may be ignored in trnaslating, but no automatic adjustment of gaps
3. No automatic adjustments to gaps made, and gaps not ignored when translating 
• File extensions for GenBank, Fasta, PHYLIP, NBRF/PIR and BioEdit Plasmid files are registered for point-and-click document opening from Windows 

Bug fixes/changes since v4.3.9:

• Two bugs that were introduced into version 4.3.9 were fixed:
1. Access Violation that would occur after previewing "Print Alignment as text"
2. Access Violation that would occur upon running mutual information analysis

Bug fixes/changes since v4.3.8:

• The program was restructured internally to use less memory and much fewer system resources.  As a result, the program loads much faster and is not as demanding of the operating system.  If you have experienced any trouble with starting BioEdit, this may solve the problem.
• Two bugs were fixed in the display of selected residues:
1. The entire selection is now highlighted correctly in very long stretches of selected residues (more than ca. 25000 residues).
2. When selecting entire columns by selecting on the sequence position ruler, the selection highlighting would sometimes get broken, with some selections not appearing highlighted. This has been fixed. 

Bug fixes/changes since v4.3.7:

• Added click-select capability fo viewing data points in the matrix plotter
• When creating a line graph from matrix data, the row selected on the matrix plotter is graphed
• When toggling between row and column views in matrix row/column graphs, the selected data point on the matrix plotter is used
• When rows or columns are scrolled through on a line graph, the selected data point on the matrix plotter (if there is one) is  updated to match
• Rows or column may be selected for an open matrix line graph by selecting a point on the matrix plotter
• Fixed a bug in memory allocation for the matrix plotter:  The last point of the matrix no longer disappears
• Matrix table reading is now more flexible (It can handle inappropriate spaces, tabs or returns in the file without giving  an error)
• Matrix plotter now reads .csv (comma-delimited) matrices as well as tab-delimited
• A bug was fixed for updating feature titles in the plasmid drawing utility:  The updated title is selected and sized correctly on the screen now
• Linear vector maps should now shade better on a grayscale laser printer (only circular maps were fixed previously)
• Moving the ends of horizontal or vertical arrows in the plasmid drawing utility now works correctly (doesn't get stuck horizontal or vertical anymore)
• A bug in the new nucleotide/protein translation view toggling was fixed:  Previously, if gaps were accidentally introduced into the last codon of a nucleotide sequence and several gaps also occurred at the end of the sequence, an error would occur when BioEdit attempted to readjust gaps to mend codons.  This should no longer be a problem

Bug fixes/changes since v4.3.6:

• The on-line help system was updated with a full searchable index and full text search capability
• Nucleotide sequences which encode proteins may be switched between their protein and nucleic acid sequences, and alignments may be edited in either view
• Simple translations of nucleic acids and reverse translations of proteins now take gaps into account rather than treating them as unknown residues
• ClustalW may now be run without modifying sequence titles to be non-redundant and 10 or few characters long
• When ClustalW is run from the accessory menu, the new alignment is automatically updated with GenBank information (features, references, accession, etc.) and full titles

Bug fixes/changes since v4.3.5:
(These changes were both made to the plasmid drawing utility)

• Grouped drawing objects now scale as a unit
• Changed feature drawing (arrows and boxes) to be more compatible with most printers

Bug fixes/changes since v4.3.4:

• Added linear vector capability
• Made titles selectable and editable
• Made vector structure selectable and mouse-movable
• All objects and labels move along with vector when moving by hand
• Restriction sites and feature labels locations adjust themselves when vector is resized 
• Bug fixed in plasmid utility:  selecting multiple restriction site labels then hitting "delete" was causing trouble with the enzyme-label links

Bug fixes/changes since v4.3.3:

• A bug in the positioning of restriction cut sites at the origin junction of circular DNA sequences was fixed.  This error occured when running a map on circular sequences that had a restriction site  that overlapped the origin and cut after the overlap point.  This would cause an error also when generating a plasmid map from such a sequence.

Bug fixes/changes since v4.3.2:

• Only one change:  The sequence editing box now behaves better, and there is no set limit on the size of the sequence that can be opened and edited in an edit box (well, actually the theoretical upper limit is10 million bases, but that would be too slow to be worth it, anyway).
• The printable documentation has been updated (It's only available for MS Word'97 or later).

Bug fixes/changes since v4.3.1:

• Fixed an error in Kyte and Doolittle hydrophobicity data (valine was entered as -4.2 instead of 4.2)
• Fixed enzyme label-position hot-linking in plasmid drawing utility
• Enzyme labels now directly linked by lines to their respective positions in the plasmid drawing utility.
• Scaling to the printer fixed for plasmid drawing
• Added arrows to drawing tools in plasmid drawing utility.
• Copy and Paste now works between plasmid documents and toolbar is updated correctly when switching between multiple plasmid documents (was a problem before).

Bug fixes/changes since v4.1.2:

• Modified hydrophobicity plotting to conform to Kyte and Doolittle mean hydrophobicity profile.
• Added file save and open capability for plasmid drawing files
• Added direct print for plasmid drawings
• Added object property editing for plasmid drawing
• Added copy and paste functions for plasmid drawing and modified copy to allow copying objects as bitmaps for pasting into other apps
• Added object ordering support in plasmid drawing utility

Bug fixes/changes since v4.1.1:

• Several bug fixes in new plasmid mapping utility:
• no longer crashes when creating a vector from a sequence containing lowercase letters
• Extra restriction enzymes no longer show up in restriction enzyme dialog box
• Feature and enzyme labels now are created as objects that may be moved and scaled
• features may now cross the orign (allowing proper control over direction)
• Scaling drawing objects works more intuitively now
• Hand-drawn lines behave as lines rather than recangular diagonals (only the ends are selected, rather than a rectangular bounding region, and ends may be moved around leaving the opposite end anchored)


The plasmid drawing utility has a long way to go.  Things that need to be added or improved include:

• More drawing tools
• Support for rotating objects
• Editing object properties after drawing them on the screen
• Direct print to the printer (copying to the clipboard produces screen-resolution, very pixellated, images)
• Plasmid file format the allows the user to save a plasmid document as an editable, vectored graphic
• Some sort of documentation (documentation for the whole program badly needs to be updated)

Bug fixes/changes since v3.1.2:

• Added plasmid drawing interface with annotation tools and polylinker view -- this is in an early stage and is not yet finished.  It may also have a couple of bugs.
• Fixed bug in multipage graphical alignment views (no longer crashes on the last page -- also made graphic view more efficient)

Bug fixes/changes since v3.1.1:

• Fixed bugs in opening of Fasta files from Mac or UNIX format (was losing the first line of sequence) 
• Fixed minor bug in opening of NBRF/PIR sequences (spaces in the title would truncate the title and tack extra characters at the beginning of the sequence 
• Fixed color matching between series lines and legend of hydrophobicity plots 
• Added scrolling/keyboard control of row/column number in line plots of mutual information matrix data

Bug fixes/changes since v3.0.1:

• Fixed font handling in edit window -- any fonts will now scale correctly with ruler and selections.
• Added hydrophobicity/hydrophobicity profiles for proteins(Kyte-Doolittle, Eisenberg, Cornette, Boyko, Parker, and Hopps-Woods scales).
• Added amino acid and nucleotide composition summaries and plots.
• Reorganized the "Sequence" menu (now has separate "Nucleic Acids" and "Protein" menus)
• Fixed bug in Mask toggling (would cause an exception if selection went beyond the end of the mask)
• Added restriction enzyme mapping/browsing by manufacturer
• Updated restriction enzyme table with the REBASE gcgenz.811 table

Bug fixes/changes since v2.1.1:

• Added zoom capability and forced data point size to data matrix plotter
• Added line/area graphing for rows of mutual information matrix data with point-and-click data examination
• Experimental three-way information (M(xyz), M(x,yz), M(xy,z) and M(xz,y)) -- doesn't seem to be very worthwhile, however.
• Added print and clipboard copy capabilities to two-dimensional graphs (so far only Entropy plots and data matrix row plots are available).
• BioEdit is now distributed with the TreeView installation package which may be installed independently of BioEdit.

Bug fixes/changes since v2.0.4:

• fixed bug in LOCUS field of GenBank files (was duplicationg part of the LOCUS in some cases
• Better handling of Macintosh-formatted GenBank files
• Automatic scrolling in Grab and Drag mode.
• Arrow key control over window scrolling
• Added horizontal scroll speed controller
• Fixed information-responsive residue shading (capital/lowercase residues no longer seen as different, and multiple gaps now reduce the alignment strength rather than increase it) 
• Uppercase/lowercase, lock/unlock and degap control of sequence selections as well as complete sequences.

Bug fixes/changes since v2.0.3:

• Automatic scrolling in document while selecting residues: Scrolling past the end no longer causes the beginning of the selection to be moved back, and scrolling paste the beginning no longer causes the window to scroll forward.
• Copy/paste: Using the normal copy function will now copy entire sequence structures as long as no residues are selected on the screen. Paste works just like Paste Sequence(s) as long as the document is not in Edit Residues mode. Copy Sequence(s) will both copy sequence structures to the BioEdit clipboard and also Fasta-formatted sequences to the Windows clipboard. 
• The New Alignment option of the File menu now works from within an alignment document.
• Consensus sequence generation no longer drops the last residue

Degapping and unlocking gaps does not cause an error when selection(s) go paste the end of a sequence.

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