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/*
* Copyright 2014 Brian Tjaden
*
* This file is part of Rockhopper.
*
* Rockhopper is free software: you can redistribute it and/or modify
* it under the terms of the GNU General Public License as published by
* the Free Software Foundation, either version 3 of the License, or
* any later version.
*
* Rockhopper is distributed in the hope that it will be useful,
* but WITHOUT ANY WARRANTY; without even the implied warranty of
* MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
* GNU General Public License for more details.
*
* You should have received a copy of the GNU General Public License
* (in the file gpl.txt) along with Rockhopper.
* If not, see <http://www.gnu.org/licenses/>.
*/
/**
* A Dictionary instance represents a dictionary of k-mers
* found in a set of sequencing reads.
*/
import java.util.HashMap;
import java.util.ArrayList;
import java.util.Collections;
import java.util.Arrays;
public class Dictionary {
/********************************************
********** Instance Variables **********
********************************************/
public Table dict;
private int size;
private ArrayList<StringBuilder> transcripts = new ArrayList<StringBuilder>();
private ArrayList<KMer> seeds;
private int seedIndex;
public DeNovoIndex bwtIndex;
/*****************************************
********** Class Variables **********
*****************************************/
private static int k; // Size of k-mer
private static char[] alphabet_1 = {'A', 'C', 'G', 'T'};
private static int[] alphabet_2 = new int[128]; // ASCII values
/**************************************
********** Constructors **********
**************************************/
public Dictionary(int k) {
Dictionary.k = k;
dict = new Table();
alphabet_2['A'] = 0;
alphabet_2['C'] = 1;
alphabet_2['G'] = 2;
alphabet_2['T'] = 3;
alphabet_2['^'] = 4;
alphabet_2['$'] = 5;
bwtIndex = new DeNovoIndex(new ArrayList<StringBuilder>()); // Empty transcript index initially
}
/*************************************************
********** Public Instance Methods **********
*************************************************/
public void add(String read) {
String read_RC = "";
if (Assembler.unstranded) read_RC = Assembler.reverseComplement(read);
for (int i=0; i<read.length()-k+1; i++) {
if (!bwtIndex.exactMatch(read, i, i+k)) { // k-mer not in BWT transcript index
if (Assembler.unstranded) { // Strand ambiguous
if (!bwtIndex.exactMatch(read_RC, read.length()-i-k, read.length()-i)) { // revComp of k-mer not in index
Long k_mer = stringToLong(read, i, i+k);
Long k_mer_RC = stringToLong(read_RC, read.length()-i-k, read.length()-i);
dict.add(k_mer, k_mer_RC);
}
} else { // Strand specific
Long k_mer = stringToLong(read, i, i+k);
dict.add(k_mer);
}
}
}
if (dict.exceedsLoadFactor()) buildTranscriptsAndClearTable(); // Table is full
}
/**
* Returns the number of unique elements in the dictionary.
*/
public int getSize() {
return size;
}
/**
* Returns the number of transcripts.
*/
public int getNumTranscripts() {
int size = 0;
for (StringBuilder sb : transcripts) {
if (sb.length() >= Assembler.minTranscriptLength) size++;
}
return size;
}
/**
* Returns the average transcript length.
*/
public int getAverageTranscriptLength() {
long length = 0;
int count = 0;
if (transcripts.size() == 0) return 0;
for (StringBuilder sb : transcripts) {
if (sb.length() >= Assembler.minTranscriptLength) {
length += sb.length();
count++;
}
}
if (count == 0) return 0;
else return (int)(length/count);
}
public void initializeReadMapping(boolean stopAfterOneHit) {
bwtIndex.initializeReadMapping(stopAfterOneHit);
}
/**
* Map the full length read to the index of assembled transcripts.
*/
public void mapFullLengthRead(String read) {
bwtIndex.exactMatch_fullRead(read);
}
/**
* Map the full length *paired-end* read to the index of assembled transcripts.
*/
public void mapFullLengthRead(String read, String read2) {
bwtIndex.exactMatch_fullRead(read, read2);
}
public void assembleTranscripts() {
size = dict.size(); // Compute size
// Extend existing transcripts
for (int i=0; i<transcripts.size(); i++) {
extendSeedForward(transcripts.get(i));
extendSeedBackward(transcripts.get(i));
}
// Create new transcripts
prepareSeeds();
Long seed = getSeed();
while (seed != null) {
StringBuilder transcript = new StringBuilder(longToString(seed));
dict.remove(seed); // Remove seed from dict
extendSeedForward(transcript);
extendSeedBackward(transcript);
seed = getSeed();
transcripts.add(transcript);
}
dict = new Table();
bwtIndex = new DeNovoIndex(transcripts);
System.gc();
}
/**************************************************
********** Private Instance Methods **********
**************************************************/
/**
* Check if the table is full.
* If so, assemble transcripts via deBruijn graph and
* clear the dictionary.
*/
private synchronized void buildTranscriptsAndClearTable() {
if (dict.exceedsLoadFactor()) { // Table is full
assembleTranscripts();
}
}
/**
* Returns the most frequently occurring k-mer subject
* to the following restrictions:
* - The seed is sufficiently expressed, i.e., sufficiently many reads supporting the k-mer
* - The information content is at least 1.5
* - The k-mer is not palindromic (deleted).
*/
private Long getSeed() {
while (seedIndex < seeds.size()) {
Long key = seeds.get(seedIndex).key;
seedIndex++;
if (dict.containsKey(key) && (informationContent(key) >= 1.5)) return key;
}
return null;
}
/**
* Since we need to repeatedly determine the best seed in the
* dictionary (an expensive operation for a hashtable), we
* create a sorted vector so that finding the best seed is
* efficient.
*/
private void prepareSeeds() {
seeds = new ArrayList<KMer>();
for (int i=0; i<dict.capacity; i++) {
int value = dict.getValueAtIndex(i);
if (value == 0) continue;
Long key = dict.getKeyAtIndex(i);
if (value >= Assembler.minSeedExpression) seeds.add(new KMer(key, value));
}
Collections.sort(seeds, Collections.reverseOrder());
seedIndex = 0;
}
/**
* Extends transcript 5' to 3'.
*/
private void extendSeedForward(StringBuilder transcript) {
boolean done = false;
while (!done) {
int max = Assembler.minExpression-1;
int maxIndex = -1;
transcript.append('?');
for (int i=0; i<alphabet_1.length; i++) {
transcript.setCharAt(transcript.length()-1, alphabet_1[i]);
Long k_mer = stringToLong(transcript, transcript.length()-k, transcript.length());
if (dict.containsKey(k_mer) && (dict.get(k_mer) > max)) {
max = dict.get(k_mer);
maxIndex = i;
}
if (Assembler.unstranded) { // Strand ambiguous
Long k_mer_RC = stringToLong(Assembler.reverseComplement(transcript.substring(transcript.length()-k)), 0, k);
if (dict.containsKey(k_mer_RC) && (dict.get(k_mer_RC) > max)) {
max = dict.get(k_mer_RC);
maxIndex = i;
}
}
}
if (maxIndex >= 0) { // Found an extension
transcript.setCharAt(transcript.length()-1, alphabet_1[maxIndex]);
Long key = stringToLong(transcript, transcript.length()-k, transcript.length());
dict.remove(key); // Remove k-mer from dict
if (Assembler.unstranded) { // Strand ambiguous
Long key_RC = stringToLong(Assembler.reverseComplement(transcript.substring(transcript.length()-k)), 0, k);
dict.remove(key_RC); // Remove k-mer from dict
}
} else { // No extension
transcript.deleteCharAt(transcript.length()-1);
done = true;
}
}
}
/**
* Extends transcript 3' to 5'.
*/
private void extendSeedBackward(StringBuilder transcript) {
transcript.reverse();
boolean done = false;
while (!done) {
int max = Assembler.minExpression-1;
int maxIndex = -1;
transcript.append('?');
for (int i=0; i<alphabet_1.length; i++) {
transcript.setCharAt(transcript.length()-1, alphabet_1[i]);
Long k_mer = stringToLong_Reverse(transcript, transcript.length()-k, transcript.length());
if (dict.containsKey(k_mer) && (dict.get(k_mer) > max)) {
max = dict.get(k_mer);
maxIndex = i;
}
if (Assembler.unstranded) { // Strand ambiguous
Long k_mer_RC = stringToLong_Reverse(Assembler.reverseComplement(transcript.substring(transcript.length()-k)), 0, k);
if (dict.containsKey(k_mer_RC) && (dict.get(k_mer_RC) > max)) {
max = dict.get(k_mer_RC);
maxIndex = i;
}
}
}
if (maxIndex >= 0) { // Found an extension
transcript.setCharAt(transcript.length()-1, alphabet_1[maxIndex]);
Long key = stringToLong_Reverse(transcript, transcript.length()-k, transcript.length());
dict.remove(key); // Remove k-mer from dict
if (Assembler.unstranded) { // Strand ambiguous
Long key_RC = stringToLong_Reverse(Assembler.reverseComplement(transcript.substring(transcript.length()-k)), 0, k);
dict.remove(key_RC); // Remove k-mer from dict
}
} else { // No extension
transcript.deleteCharAt(transcript.length()-1);
done = true;
}
}
transcript.reverse();
}
/***********************************************
********** Private Class Methods **********
***********************************************/
private static Long stringToLong(String s, int index1, int index2) {
long num = 0;
for (int i=index1; i<index2; i++) {
num = num << 2;
num += charToInt(s.charAt(i));
}
return new Long(num);
}
private static Long stringToLong(StringBuilder sb, int index1, int index2) {
long num = 0;
for (int i=index1; i<index2; i++) {
num = num << 2;
num += charToInt(sb.charAt(i));
}
return new Long(num);
}
private static Long stringToLong_Reverse(String s, int index1, int index2) {
long num = 0;
for (int i=index2-1; i>=index1; i--) {
num = num << 2;
num += charToInt(s.charAt(i));
}
return new Long(num);
}
private static Long stringToLong_Reverse(StringBuilder sb, int index1, int index2) {
long num = 0;
for (int i=index2-1; i>=index1; i--) {
num = num << 2;
num += charToInt(sb.charAt(i));
}
return new Long(num);
}
private static String longToString(Long key) {
long num = key.longValue();
StringBuilder sb = new StringBuilder(k+1);
for (int i=0; i<k; i++) {
sb.append(intToChar((int)num & 3));
num = num >>> 2;
}
return sb.reverse().toString();
}
public static int charToInt(char c) {
return alphabet_2[c];
}
private static char intToChar(int num) {
return alphabet_1[num];
}
private static double informationContent(Long k_mer) {
double[] counts = new double[4];
long num = k_mer.longValue();
for (int i=0; i<k; i++) {
counts[((int)num & 3)] += 1.0;
num = num >>> 2;
}
double sum = 0.0;
for (int i=0; i<counts.length; i++) sum += counts[i];
double informationContent = 0.0;
for (int i=0; i<counts.length; i++) {
if (counts[i] > 0.0) {
double frequency = counts[i] / sum;
informationContent += frequency * Math.log(frequency) / Math.log(2.0);
}
}
return 0.0 - informationContent;
}
/*************************************
********** Main Method **********
*************************************/
public static void main(String[] args) {
int k = 25;
Dictionary d = new Dictionary(k);
String s = "AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAG";
System.out.println(s);
for (int i=0; i<d.dict.capacity; i++) {
int value = d.dict.getValueAtIndex(i);
if (value == 0) continue;
Long key = d.dict.getKeyAtIndex(i);
System.out.println(longToString(key) + "\t" + value);
}
}
}
/**************************************
********** Helper Class **********
**************************************/
class KMer implements Comparable<KMer> {
public Long key;
public Integer count;
public KMer(Long key, Integer count) {
this.key = key;
this.count = count;
}
public int compareTo(KMer k) {
return count.compareTo(k.count);
}
}
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