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//
// BCSequence.m
// BioCocoa
//
// Created by Koen van der Drift on 12/14/2004.
// Copyright (c) 2003-2009 The BioCocoa Project.
// All rights reserved.
//
// Redistribution and use in source and binary forms, with or without
// modification, are permitted provided that the following conditions
// are met:
// 1. Redistributions of source code must retain the above copyright
// notice, this list of conditions and the following disclaimer.
// 2. Redistributions in binary form must reproduce the above copyright
// notice, this list of conditions and the following disclaimer in the
// documentation and/or other materials provided with the distribution.
// 3. The name of the author may not be used to endorse or promote products
// derived from this software without specific prior written permission.
//
// THIS SOFTWARE IS PROVIDED BY THE AUTHOR ``AS IS'' AND ANY EXPRESS OR
// IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED WARRANTIES
// OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE DISCLAIMED.
// IN NO EVENT SHALL THE AUTHOR BE LIABLE FOR ANY DIRECT, INDIRECT,
// INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT
// NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE,
// DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY
// THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT
// (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF
// THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
#import "BCSequence.h"
#import "BCAnnotation.h"
#import "BCFoundationDefines.h"
#import "BCSymbol.h"
#import "BCAminoAcid.h"
#import "BCSymbolSet.h"
#import "BCToolSequenceFinder.h"
#import "BCToolComplement.h"
#import "BCUtilData.h"
#import "BCInternal.h"
@implementation BCSequence
// TODO:
// MOVE MUTABLE METHODS TO ...
// UPDATE THE REVERSE METHOD - SHOULD THIS BE DONE STRING-BASED?
// UPDATE MORE HEADERDOC INFORMATION
// LOOK AGAIN AT SYMBOLATINDEX METHOD
// ADD METHODS FOR NSDATA <-> NSSTRING CONVERSIONS, PROBABLY NOT IN THIS CLASS
// FIX COMPILER WARNINGS
// ....
////////////////////////////////////////////////////////////////////////////
#if 0
#pragma mark
#pragma mark INITIALIZATION METHODS
#endif
//
// INITIALIZATION METHODS
////////////////////////////////////////////////////////////////////////////
// designated initializer
- (id)initWithString:(NSString *)aString symbolSet:(BCSymbolSet *)aSet
{
if ( (self = [super init]) )
{
if ( aString != nil )
{
if ( aSet == nil )
{
aSet = [BCSymbolSet symbolSetForSequenceType: [self sequenceTypeForString: aString]];
}
//let the set check the chars
NSString *finalString = [aSet stringByRemovingUnknownCharsFromString: aString];
// fill the NSData buffer with the contents of the NSString
sequenceData = [[finalString dataUsingEncoding: NSUTF8StringEncoding] retain];
}
else
{
sequenceData = nil;
}
symbolSet = [aSet retain];
sequenceType = [aSet sequenceType];
annotations = nil;
symbolArray = nil;
}
return self;
}
- (id)initWithData:(NSData *)aData symbolSet:(BCSymbolSet *)aSet
{
if ( (self = [super init]) ) {
if ( aData != nil ) {
if ( aSet == nil ) {
aSet = [BCSymbolSet symbolSetForSequenceType: [self sequenceTypeForData: aData]];
}
// let the set check the chars
sequenceData = [aSet dataByRemovingUnknownCharsFromData: aData];
[sequenceData retain];
} else {
sequenceData = nil;
}
symbolSet = [aSet retain];
sequenceType = [aSet sequenceType];
annotations = nil;
symbolArray = nil;
}
return self;
}
- (id)initWithSymbolArray:(NSArray *)anArray symbolSet:(BCSymbolSet *)aSet
{
if ( (self = [super init]) )
{
if ( aSet==nil )
{
aSet = [BCSymbolSet symbolSetForSequenceType: [self sequenceTypeForSymbolArray: anArray]];
}
//let the set check the symbols
NSArray *finalArray=[aSet arrayByRemovingUnknownSymbolsFromArray:anArray];
symbolArray=[[NSMutableArray alloc] initWithArray:finalArray];
// fill the NSData buffer with the contents of the array of symbols
sequenceData = [[[self sequenceStringFromSymbolArray: symbolArray]
dataUsingEncoding: NSUTF8StringEncoding] retain];
symbolSet=[aSet retain];
annotations=nil;
sequenceType = [symbolSet sequenceType];
}
return self;
}
- (id)initWithSymbolArray:(NSArray *)anArray
{
return [self initWithSymbolArray:anArray symbolSet: nil];
}
// returns an empty sequence by calling the designated initializer
- (id)init
{
return [self initWithString:[NSString string] symbolSet:[BCSymbolSet unknownSymbolSet]];
}
- (id)initWithString:(NSString*)aString
{
return [self initWithString:aString symbolSet: nil];
}
- (id)initWithString:(NSString*)aString range:(NSRange)aRange
{
return [self initWithString:[aString substringWithRange:aRange]];
}
- (id)initWithString:(NSString*)aString range:(NSRange)aRange symbolSet:(BCSymbolSet *)aSet
{
return [self initWithString:[aString substringWithRange:aRange] symbolSet: aSet];
}
- (id)initWithThreeLetterString:(NSString*)aString symbolSet:(BCSymbolSet *)aSet
{
return [self initWithString:
[self convertThreeLetterStringToOneLetterString: aString symbolSet: aSet] symbolSet: aSet];
}
+ (BCSequence *)sequenceWithString: (NSString *)aString
{
return [[[BCSequence alloc] initWithString:aString] autorelease];
}
+ (BCSequence *)sequenceWithString:(NSString *)aString symbolSet:(BCSymbolSet *)aSet
{
return [[[BCSequence alloc] initWithString:aString symbolSet:aSet] autorelease];
}
+ (BCSequence *)sequenceWithThreeLetterString:(NSString *)aString symbolSet:(BCSymbolSet *)aSet
{
return [[[BCSequence alloc] initWithThreeLetterString: aString symbolSet:aSet] autorelease];
}
+ (BCSequence *)sequenceWithSymbolArray:(NSArray *)entry
{
return [[[BCSequence alloc] initWithSymbolArray:entry] autorelease];
}
+ (BCSequence *)sequenceWithSymbolArray:(NSArray *)entry symbolSet: (BCSymbolSet *)aSet;
{
return [[[BCSequence alloc] initWithSymbolArray:entry symbolSet: aSet] autorelease];
}
+ (BCSequence *) objectForSavedRepresentation: (NSString *)aSequence
{
return [[[BCSequence alloc] initWithString: aSequence] autorelease];
}
- (NSString *)convertThreeLetterStringToOneLetterString:(NSString *)aString symbolSet: (BCSymbolSet *)aSet
{
int i;
NSArray *anArray = [aString componentsSeparatedByString:@" "];
NSString *oneLetterCode, *threeLetterCode;
NSMutableString *convertedString = [[NSMutableString alloc] initWithString: @""];
// build a temporary dictionary with the one-letter code as objects and the three-letter code as keys
// the easiest seems to use a symbolset and iterate over all the symbols
// for now only works for amino acids. However, if 3-letter codes are also available
// for nucleotides, the code can be extended to use BCSymbol. That means that the ivar threeLetterCode
// should be moved to BCSymbol from BCAminoAcid
NSArray *symArray = [[BCSymbolSet proteinSymbolSet] allSymbols];
BCAminoAcid *symbol;
NSMutableDictionary *symbolDict = [NSMutableDictionary dictionaryWithCapacity: [symArray count]];
for (i = 0; i < [symArray count]; i++)
{
symbol = [symArray objectAtIndex: i];
[symbolDict setObject: [symbol symbolString] forKey: [symbol threeLetterCode]];
}
// now we have the temp symbolDict, iterate over the sequence (in 3-letter code)
// and create a new string using the 1-letter code
for (i = 0; i < [anArray count]; i++)
{
threeLetterCode = [anArray objectAtIndex: i];
oneLetterCode = [symbolDict objectForKey: [threeLetterCode capitalizedString]];
if ( oneLetterCode )
{
[convertedString appendString: oneLetterCode];
}
}
return [convertedString autorelease];
}
// BCSequence is immutable, no need to copy anything just retain and return self
- (id)copyWithZone:(NSZone *)zone
{
return [self retain];
}
- (void)dealloc
{
[sequenceData release];
[symbolSet release];
[annotations release];
[self clearSymbolArray];
[super dealloc];
}
////////////////////////////////////////////////////////////////////////////
#if 0
#pragma mark
#pragma mark SEQUENCE TYPE DETERMINATION
#endif
//
// INFORMATIONAL METHODS
////////////////////////////////////////////////////////////////////////////
// This method guesses the sequence type based on a string.
// The method creates new sequences of the different types
// and checks which one results in the longer sequence,
// which is also the one having the lowest number of unknown symbols.
- (BCSequenceType)sequenceTypeForString:(NSString *)string
{
// bestSequenceType = best sequence type so far
// bestSymbolCount = the length of the best sequence type so far
BCSequence *testSequence;
BCSequenceType bestSequenceType;
unsigned int bestSymbolCount;
// use a DNA sequence to initialize the values of bestSequenceType and bestSymbolCount
testSequence=[BCSequence sequenceWithString:string symbolSet: [BCSymbolSet dnaSymbolSet]];
bestSequenceType=BCSequenceTypeDNA;
bestSymbolCount=[testSequence length];
// test RNA sequence
testSequence=[BCSequence sequenceWithString:string symbolSet: [BCSymbolSet rnaSymbolSet]];
if ([testSequence length]>bestSymbolCount) {
bestSequenceType=BCSequenceTypeRNA;
bestSymbolCount=[testSequence length];
}
// test Protein sequence
testSequence=[BCSequence sequenceWithString:string symbolSet: [BCSymbolSet proteinSymbolSet]];
if ([testSequence length]>bestSymbolCount) {
bestSequenceType=BCSequenceTypeProtein;
bestSymbolCount=[testSequence length];
}
//TO DO: is it a BCSequenceCodon?
// * symbols = DNA or RNA > protein
// * length = multiple of three
// * first 3 letters = ATG / AUG
// * no stop codon, except at the end
return bestSequenceType;
}
// This method guesses the sequence type for data
- (BCSequenceType)sequenceTypeForData:(NSData *)aData
{
unsigned char *seqData = (unsigned char *)[aData bytes];
unsigned i, len = [aData length];
// hopefully can determine in first 10,000 symbols
if (len > 10000) len = 10000;
BCSymbolSet *dna = [BCSymbolSet dnaSymbolSet];
BCSymbolSet *rna = [BCSymbolSet rnaSymbolSet];
BCSymbolSet *prot = [BCSymbolSet proteinSymbolSet];
unsigned dnaCount = 0, rnaCount = 0, protCount = 0;
// bestSequenceType = best sequence type so far
// bestSymbolCount = the length of the best sequence type so far
BCSequenceType bestSequenceType;
// use a DNA sequence to initialize the values of bestSequenceType and bestSymbolCount
for (i = 0; i < len; ++i) {
if ([dna symbolForChar: seqData[i]]) ++dnaCount;
if ([rna symbolForChar: seqData[i]]) ++rnaCount;
if ([prot symbolForChar: seqData[i]]) ++protCount;
}
// Note that the DNA and RNA symbols is a subset of protein symbols
// so assume DNA/RNA and only use protein if count is higher
if (dnaCount > rnaCount) {
if (protCount > dnaCount) {
bestSequenceType = BCSequenceTypeProtein;
} else {
bestSequenceType = BCSequenceTypeDNA;
}
} else {
if (protCount > rnaCount) {
bestSequenceType = BCSequenceTypeProtein;
} else {
bestSequenceType = BCSequenceTypeRNA;
}
}
//TO DO: is it a BCSequenceCodon?
// * symbols = DNA or RNA > protein
// * length = multiple of three
// * first 3 letters = ATG / AUG
// * no stop codon, except at the end
return bestSequenceType;
}
// This method guesses the sequence type based on an NSArray of BCSymbol.
// The method creates new sequences of the different types
// and checks which one results in the longer sequence,
// which is also the one having the lowest number of unknown symbols.
- (BCSequenceType)sequenceTypeForSymbolArray:(NSArray *)anArray;
{
// bestSequenceType = best sequence type so far
// bestSymbolCount = the length of the best sequence type so far
BCSequence *testSequence;
BCSequenceType bestSequenceType;
unsigned int bestSymbolCount;
// use DNA sequence to initialize the values of bestSequenceType and bestSymbolCount
testSequence=[BCSequence sequenceWithSymbolArray:anArray symbolSet: [BCSymbolSet dnaSymbolSet]];
bestSequenceType=BCSequenceTypeDNA;
bestSymbolCount=[testSequence length];
// test RNA sequence
testSequence=[BCSequence sequenceWithSymbolArray:anArray symbolSet: [BCSymbolSet rnaSymbolSet]];
if ([testSequence length]>bestSymbolCount) {
bestSequenceType=BCSequenceTypeRNA;
bestSymbolCount=[testSequence length];
}
// test protein sequence
testSequence=[BCSequence sequenceWithSymbolArray:anArray symbolSet: [BCSymbolSet proteinSymbolSet]];
if ([testSequence length]>bestSymbolCount) {
bestSequenceType=BCSequenceTypeProtein;
bestSymbolCount=[testSequence length];
}
//TO DO: is it a BCSequenceCodon?
// * symbols = DNA or RNA > protein
// * length = multiple of three
// * first 3 letters = ATG / AUG
// * no stop codon, except at the end
return bestSequenceType;
}
////////////////////////////////////////////////////////////////////////////
#if 0
#pragma mark
#pragma mark OBTAINING SEQUENCE INFORMATION
#endif
//
// INFORMATIONAL METHODS
////////////////////////////////////////////////////////////////////////////
- (NSData *) sequenceData
{
return sequenceData;
}
- (const unsigned char *) bytes
{
return (const unsigned char *)[[self sequenceData] bytes];
}
- (BCSymbolSet *)symbolSet
{
return symbolSet;
}
// we can now allow to modify a symbolset, eg from strict -> non strict
- (void)setSymbolSet:(BCSymbolSet *)set
{
[set retain];
[symbolSet release];
symbolSet = set;
}
- (BCSequenceType)sequenceType
{
return sequenceType;
}
// should this be commented out?
/*
- (void) setSequenceType:(BCSequenceType)aType
{
sequenceType = aType;
}
*/
- (unsigned int) length
{
return [[self sequenceData] length];
}
- (BCSymbol *)symbolAtIndex: (int)theIndex
{
if ( theIndex < [self length] )
{
BCSymbol *aSymbol;
#if 1
unsigned char c = [[self sequenceData] charAtIndex: theIndex];
aSymbol = [[self symbolSet] symbolForChar: c];
#else
// or maybe use getBytes - not faster according to reply on CocoaDev-list
unsigned char buffer;
[[self sequenceData] getBytes: &buffer range: NSMakeRange( theIndex, 1 )];
aSymbol = [[self symbolSet] symbolForChar: buffer];
#endif
return aSymbol;
}
return nil;
}
- (BOOL) containsAmbiguousSymbols {
BCSymbol *aSymbol;
DECLARE_INDEX(loopCounter);
int theLimit = [symbolArray count];
for ( loopCounter = 0 ; loopCounter < theLimit ; loopCounter++ ) {
aSymbol = (BCSymbol *)ARRAY_GET_VALUE_AT_INDEX(symbolArray, loopCounter);
if ( [aSymbol isCompoundSymbol] )
return YES;
}
return NO;
}
- (NSArray *)symbolArray
{
if ( sequenceData == nil )
{
return nil;
}
if ( symbolArray == nil )
{
// creates a symbol array from the NSData sequence
const unsigned char *data;
unsigned int i, len;
BCSymbol *aSymbol;
data = [self bytes];
len = strlen((char *)data);
NSMutableArray *anArray = [NSMutableArray array];
for (i = 0; i < len; i++)
{
if ( (aSymbol = [[self symbolSet] symbolForChar: data[i]]) )
{
[anArray addObject: aSymbol];
}
}
symbolArray = [[NSArray alloc] initWithArray: anArray];
}
return symbolArray;
}
- (void)clearSymbolArray
{
[symbolArray release];
symbolArray = nil;
}
// TO DO : use BCSymbolSet for filtering
// DO WE STILL NEED THIS METHOD ??
- (void) setSymbolArray: (NSArray *) anArray
{
[symbolArray release];
symbolArray = [[NSMutableArray alloc] init];
id aSymbol;
DECLARE_INDEX(loopCounter);
int theLimit = [anArray count];
for ( loopCounter = 0 ; loopCounter < theLimit ; loopCounter++ ) {
aSymbol = (id)ARRAY_GET_VALUE_AT_INDEX(anArray, loopCounter);
ARRAY_APPEND_VALUE((NSMutableArray *)symbolArray, aSymbol);
}
}
- (NSArray *)subSymbolArrayInRange:(NSRange)aRange
{
if ( aRange.location + aRange.length > [symbolArray count] )
return nil;
return [symbolArray subarrayWithRange: aRange];
}
- (NSString*)sequenceString
{
unsigned int length = [self length];
if ( length )
return [self subSequenceStringInRange: NSMakeRange( 0, length ) ];
else
return @""; // return empty string, not nil.
}
- (NSString *)subSequenceStringInRange:(NSRange)aRange
{
if ( aRange.location + aRange.length > [self length] )
return nil;
NSData *data = [[self sequenceData] subdataWithRange: aRange]; // Man, I love Cocoa !!
NSString *theReturn = [[NSString alloc] initWithData: data encoding: NSUTF8StringEncoding];
return theReturn;
}
- (NSString *)sequenceStringFromSymbolArray:(NSArray *)anArray
{
NSMutableString *symbols = [NSMutableString string];
BCSymbol *symbol;
int i;
for ( i = 0; i < [anArray count]; i++)
{
symbol = [anArray objectAtIndex: i];
[symbols appendString: [symbol symbolString]];
}
return symbols;
}
- (BCSequence *)subSequenceInRange:(NSRange)aRange {
if ( aRange.location + aRange.length > [symbolArray count] )
return nil;
return [BCSequence sequenceWithSymbolArray: [symbolArray subarrayWithRange: aRange]];
}
- (NSString *) savableRepresentation {
return [self sequenceString];
}
- (NSString *) description {
return [self sequenceString];
}
- (void) addAnnotation:(BCAnnotation *)annotation
{
[self addAnnotation: (id)[annotation content] forKey: [annotation name]];
}
- (void) addAnnotation:(NSString *)annotation forKey: (NSString *) key
{
NSMutableString *oldValue;
BCAnnotation *oldAnnotation, *newAnnotation;
if ( annotations == nil )
{
annotations = [[NSMutableDictionary alloc] init];
}
// If key already exists, then we need to append the value, instead of replacing it.
// This will happen when annotations are in the entry in multiple lanes.
oldAnnotation = (BCAnnotation *) [[self annotations] valueForKey: key];
if ( oldAnnotation )
{
oldValue = [[oldAnnotation content] mutableCopy];
[oldValue appendString: @"\n"];
[oldValue appendString: annotation];
newAnnotation = [[BCAnnotation alloc] initWithName: key content: oldValue];
}
else
{
newAnnotation = [[BCAnnotation alloc] initWithName: key content: annotation];
}
[[self annotations] setObject: newAnnotation forKey: key];
}
- (id) annotationForKey: (NSString *) key
{
return [[self annotations] objectForKey: key];
}
- (NSMutableDictionary *) annotations
{
return annotations;
}
//- (void) setAnnotations:(NSMutableDictionary *)aDict
//{
// [aDict retain];
// [annotations release];
// annotations=aDict;
//}
////////////////////////////////////////////////////////////////////////////
#if 0
#pragma mark
#pragma mark DERIVING RELATED SEQUENCES
#endif
// DERIVING OTHER SEQUENCES
////////////////////////////////////////////////////////////////////////////
- (BCSequence *) reverse
{
#if 1
NSMutableArray *theReverse = [NSMutableArray array];
BCSymbol *aSymbol;
DECLARE_INDEX(loopCounter);
int theLimit = [[self symbolArray] count]; // or use [self length] ???
for ( loopCounter = 0 ; loopCounter < theLimit ; loopCounter++ ) {
aSymbol = (id)ARRAY_GET_VALUE_AT_INDEX(symbolArray, loopCounter);
ARRAY_INSERT_VALUE_AT_INDEX(theReverse, 0, aSymbol);
}
return [BCSequence sequenceWithSymbolArray: theReverse symbolSet: [self symbolSet]];
#else
NSMutableData *reverseSequence = [[NSMutableData alloc] initWithLength: [self length]];
const unsigned char *normal = [self bytes];
unsigned char *reverse = [reverseSequence mutableBytes];
unsigned int len = strlen( (char *)normal );
unsigned i, j;
j = 0;
for(i = len; i >= 0; --i)
{
reverse[j] = normal[i];
j++;
}
NSString *reverseString = [[NSString alloc] initWithData: reverseSequence encoding: NSUTF8StringEncoding];
return [[BCSequence alloc] initWithString: [reverseString autorelease] symbolSet: [self symbolSet]];
#endif
}
- (BCSequence *)complement
{
BCToolComplement *complementTool = [BCToolComplement complementToolWithSequence: self];
return [complementTool sequenceComplement];
}
- (BCSequence *) reverseComplement
{
BCToolComplement *complementTool = [BCToolComplement complementToolWithSequence: self];
[complementTool setReverse: YES];
return [complementTool sequenceComplement];
}
////////////////////////////////////////////////////////////////////////////
////////////////////////////////////////////////////////////////////////////
#if 0
#pragma mark
#pragma mark MANIPULATING SEQUENCE CONTENTS
#endif
//
// INFORMATIONAL METHODS
////////////////////////////////////////////////////////////////////////////
// THIS SHOULD ALL GO INTO THE MUTABLE SEQUENCE CLASS
- (void)removeSymbolsInRange:(NSRange)aRange
{
if ( aRange.location + aRange.length > [symbolArray count] )
return;
// [symbolArray removeObjectsInRange: aRange];
}
- (void)removeSymbolAtIndex:(int)index
{
if ( index > [symbolArray count] - 1 )
return;
// [symbolArray removeObjectAtIndex:index];
}
// TO DO : use BCSymbolSet for filtering //
- (void)insertSymbolsFromSequence:(BCSequence *)entry atIndex:(int)index
{
if ( index > [symbolArray count] - 1 )
return;
// [symbolArray replaceObjectsInRange:NSMakeRange(index,0) withObjectsFromArray:[entry symbolArray]];
}
////////////////////////////////////////////////////////////////////////////
#if 0
#pragma mark
#pragma mark FINDING SUBSEQUENCES
#endif
// FINDING SUBSEQUENCES
////////////////////////////////////////////////////////////////////////////
- (NSArray *) findSequence: (BCSequence *) entry
{
return [self findSequence: entry usingStrict: NO];
}
- (NSArray *) findSequence: (BCSequence *) entry usingStrict: (BOOL) strict
{
return [self findSequence: entry usingStrict: strict firstOnly: NO];
}
- (NSArray *) findSequence: (BCSequence *) entry usingStrict: (BOOL) strict firstOnly: (BOOL) firstOnly
{
return [self findSequence: entry usingStrict: strict
firstOnly: NO usingSearchRange: NSMakeRange(0, [self length])];
}
- (NSArray *) findSequence: (BCSequence *) entry usingStrict: (BOOL) strict
firstOnly: (BOOL) firstOnly usingSearchRange: (NSRange) range
{
BCToolSequenceFinder *sequenceFinder = [BCToolSequenceFinder sequenceFinderWithSequence: self];
[sequenceFinder setStrict: strict];
[sequenceFinder setFirstOnly: firstOnly];
[sequenceFinder setSearchRange: range];
return [sequenceFinder findSequence: entry];
}
@end
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