LocalAlignmentStringKernel.cpp

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/*
 * Compute the local alignment kernel
 *
 * Largely based on LAkernel.c (version 0.3)
 *
 * Copyright 2003 Jean-Philippe Vert
 * Copyright 2005 Jean-Philippe Vert, Hiroto Saigo
 *
 * Shogun specific adjustments Written (W) 2007-2008,2010 Soeren Sonnenburg
 * 
 * Reference:
 * H. Saigo, J.-P. Vert, T. Akutsu and N. Ueda, "Protein homology
 * detection using string alignment kernels", Bioinformatics,
 * vol.20, p.1682-1689, 2004.
 * 
 * This program 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
 * (at your option) any later version.
 */

#include <stdlib.h>
#include <stdio.h>
#include <math.h>
#include <ctype.h>
#include <string.h>
#include <shogun/kernel/LocalAlignmentStringKernel.h>

using namespace shogun;

/****************/
/* The alphabet */
/****************/

#define NAA 20                                  /* Number of amino-acids */
#define NLET 26                                 /* Number of letters in the alphabet */
const char* CLocalAlignmentStringKernel::aaList= "ARNDCQEGHILKMFPSTWYV";    /* The list of amino acids */

/*****************/
/* SW parameters */
/*****************/

/* mutation matrix */
const int32_t CLocalAlignmentStringKernel::blosum[] = {
  6,
 -2,   8,
 -2,  -1,   9,
  -3,  -2,   2,   9,
  -1,  -5,  -4,  -5,  13,
  -1,   1,   0,   0,  -4,   8,
  -1,   0,   0,   2,  -5,   3,   7,
  0,  -3,  -1,  -2,  -4,  -3,  -3,   8,
  -2,   0,   1,  -2,  -4,   1,   0,  -3,  11,
  -2,  -5,  -5,  -5,  -2,  -4,  -5,  -6,  -5,   6,
  -2,  -3,  -5,  -5,  -2,  -3,  -4,  -5,  -4,   2,   6,
  -1,   3,   0,  -1,  -5,   2,   1,  -2,  -1,  -4,  -4,   7,
  -1,  -2,  -3,  -5,  -2,  -1,  -3,  -4,  -2,   2,   3,  -2,   8,
  -3,  -4,  -5,  -5,  -4,  -5,  -5,  -5,  -2,   0,   1,  -5,   0,   9,
  -1,  -3,  -3,  -2,  -4,  -2,  -2,  -3,  -3,  -4,  -4,  -2,  -4,  -5,  11,
  2,  -1,   1,   0,  -1,   0,   0,   0,  -1,  -4,  -4,   0,  -2,  -4,  -1,   6,
  0,  -2,   0,  -2,  -1,  -1,  -1,  -2,  -3,  -1,  -2,  -1,  -1,  -3,  -2,   2,   7,
  -4,  -4,  -6,  -6,  -3,  -3,  -4,  -4,  -4,  -4,  -2,  -4,  -2,   1,  -6,  -4,  -4,  16,
  -3,  -3,  -3,  -5,  -4,  -2,  -3,  -5,   3,  -2,  -2,  -3,  -1,   4,  -4,  -3,  -2,   3,  10,
  0,  -4,  -4,  -5,  -1,  -3,  -4,  -5,  -5,   4,   1,  -3,   1,  -1,  -4,  -2,   0,  -4,  -2,   6};

/* Index corresponding to the (i,j) entry (i,j=0..19) in the blosum matrix */
#define BINDEX(i,j) (((i)>(j))?(j)+(((i)*(i+1))/2):(i)+(((j)*(j+1))/2))

/*********************
 * Kernel parameters *
 *********************/

#define SCALING 0.1           /* Factor to scale all SW parameters */

/* If you want to compute the sum over all local alignments (to get a valid kernel), uncomment the following line : */
/* If x=log(a) and y=log(b), compute log(a+b) : */
/*
#define LOGP(x,y) (((x)>(y))?(x)+log1p(exp((y)-(x))):(y)+log1p(exp((x)-(y))))
*/

#define LOGP(x,y) LogSum(x,y)

/* OR if you want to compute the score of the best local alignment (to get the SW score by Viterbi), uncomment the following line : */
/*
#define LOGP(x,y) (((x)>(y))?(x):(y))
*/

/* Usefule constants */
#define LOG0 -10000          /* log(0) */
#define INTSCALE 1000.0      /* critical for speed and precise computation*/

int32_t CLocalAlignmentStringKernel::logsum_lookup[LOGSUM_TBL];

CLocalAlignmentStringKernel::CLocalAlignmentStringKernel(int32_t size)
: CStringKernel<char>(size)
{
    init();
    init_static_variables();
}

CLocalAlignmentStringKernel::CLocalAlignmentStringKernel(
    CStringFeatures<char>* l, CStringFeatures<char>* r,
    float64_t opening, float64_t extension)
: CStringKernel<char>()
{
    init();
    m_opening=opening;
    m_extension=extension;
    init_static_variables();
    init(l, r);
}

CLocalAlignmentStringKernel::~CLocalAlignmentStringKernel()
{
    cleanup();
}

bool CLocalAlignmentStringKernel::init(CFeatures* l, CFeatures* r)
{
    CStringKernel<char>::init(l, r);
    initialized = true;
    return init_normalizer();
}

void CLocalAlignmentStringKernel::cleanup()
{
    SG_FREE(scaled_blosum);
    scaled_blosum=NULL;

    SG_FREE(isAA);
    isAA=NULL;
    SG_FREE(aaIndex);
    aaIndex=NULL;

    CKernel::cleanup();
}

/* LogSum - default log funciotion. fast, but not exact */
/* LogSum2 - precise, but slow. Note that these two functions need different figure types  */

void CLocalAlignmentStringKernel::init_logsum(void){
  int32_t i;
  for (i = 0; i < LOGSUM_TBL; i++) 
    logsum_lookup[i] = (int32_t) (INTSCALE*
                   (log(1.+exp( (float32_t) -i/INTSCALE))));
}

int32_t CLocalAlignmentStringKernel::LogSum(int32_t p1, int32_t p2)
{
    int32_t diff;
    static int32_t firsttime=1;

    if (firsttime)
    {
        init_logsum();
        firsttime =0;
    }

    diff=p1-p2;
    if (diff>=LOGSUM_TBL) return p1;
    else if (diff<=-LOGSUM_TBL) return p2;
    else if (diff>0) return p1+logsum_lookup[diff];
    else return p2+logsum_lookup[-diff];
}


float32_t CLocalAlignmentStringKernel::LogSum2(float32_t p1, float32_t p2)
{
  if (p1 > p2)
    return (p1-p2 > 50.) ? p1 : p1 + log(1. + exp(p2-p1));
  else
    return (p2-p1 > 50.) ? p2 : p2 + log(1. + exp(p1-p2));
}


void CLocalAlignmentStringKernel::init_static_variables()
     /* Initialize all static variables. This function should be called once before computing the first pair HMM score */
{
  register int32_t i;

  /* Initialization of the array which gives the position of each amino-acid in the set of amino-acid */
  if ((aaIndex=(int32_t *)calloc(NLET,sizeof(int32_t))) == NULL)
    SG_ERROR("run out o memory");
  for (i=0;i<NAA;i++) 
    aaIndex[aaList[i]-'A']=i;
  
  /* Initialization of the array which indicates whether a char is an amino-acid */
  if ((isAA=(int32_t *)calloc(256,sizeof(int32_t))) == NULL)
    SG_ERROR("run out of memory");
  for (i=0;i<NAA;i++) 
    isAA[(int32_t)aaList[i]]=1;

  /* Scale the blossum matrix */
  for (i=0 ; i<NAA*(NAA+1)/2; i++)
      scaled_blosum[i] = (int32_t) floor(blosum[i]*SCALING*INTSCALE);


  /* Scale of gap penalties */
  m_opening = (int32_t) floor(m_opening * SCALING*INTSCALE);
  m_extension = (int32_t) floor(m_extension * SCALING*INTSCALE);
}



/* Implementation of the
 * convolution kernel which generalizes the Smith-Waterman algorithm
 */
float64_t CLocalAlignmentStringKernel::LAkernelcompute(
    int32_t* aaX, int32_t* aaY, /* the two amino-acid sequences (as sequences of indexes in [0..NAA-1] indicating the position of the amino-acid in the variable 'aaList') */
    int32_t nX, int32_t nY /* the lengths of both sequences */)
{
   register int32_t
    i,j,                /* loop indexes */
    cur, old,           /* to indicate the array to use (0 or 1) */
    curpos, frompos;    /* position in an array */

   int32_t
    *logX,           /* arrays to store the log-values of each state */
    *logY,
    *logM,
    *logX2,
    *logY2,

    aux , aux2;/* , aux3 , aux4 , aux5;*/
  int32_t
    cl;                /* length of a column for the dynamic programming */

  /*
  printf("now computing pairHMM between %d and %d:\n",nX,nY);
  for (i=0;i<nX;printf("%d ",aaX[i++]));
  printf("\n and \n");
  for (i=0;i<nY;printf("%d ",aaY[i++]));
  printf("\n");
  */

  /* Initialization of the arrays */
  /* Each array stores two successive columns of the (nX+1)x(nY+1) table used in dynamic programming */
  cl = nY+1;           /* each column stores the positions in the aaY sequence, plus a position at zero */

  logM=SG_MALLOC(int32_t, 2*cl);
  logX=SG_MALLOC(int32_t, 2*cl);
  logY=SG_MALLOC(int32_t, 2*cl);
  logX2=SG_MALLOC(int32_t, 2*cl);
  logY2=SG_MALLOC(int32_t, 2*cl);

  /************************************************/
  /* First iteration : initialization of column 0 */
  /************************************************/
  /* The log=proabilities of each state are initialized for the first column (x=0,y=0..nY) */

  for (j=0;j<cl;j++) {
    logM[j]=LOG0;
    logX[j]=LOG0;
    logY[j]=LOG0;
    logX2[j]=LOG0;
    logY2[j]=LOG0;

  }

  /* Update column order */
  cur = 1;      /* Indexes [0..cl-1] are used to process the next column */
  old = 0;      /* Indexes [cl..2*cl-1] were used for column 0 */


  /************************************************/
  /* Next iterations : processing columns 1 .. nX */
  /************************************************/

  /* Main loop to vary the position in aaX : i=1..nX */
  for (i=1;i<=nX;i++) {

    /* Special update for positions (i=1..nX,j=0) */
    curpos = cur*cl;                  /* index of the state (i,0) */
    logM[curpos] = LOG0; 
    logX[curpos] = LOG0; 
    logY[curpos] = LOG0; 
    logX2[curpos] = LOG0; 
    logY2[curpos] = LOG0; 

    /* Secondary loop to vary the position in aaY : j=1..nY */
    for (j=1;j<=nY;j++) {

      curpos = cur*cl + j;            /* index of the state (i,j) */

      /* Update for states which emit X only */
      /***************************************/

      frompos = old*cl + j;            /* index of the state (i-1,j) */
      
      /* State RX */
      logX[curpos] = LOGP( - m_opening + logM[frompos] , - m_extension + logX[frompos] );
      /*      printf("%.5f\n",logX[curpos]);*/
      /*      printf("%.5f\n",logX_B[curpos]);*/
      /* State RX2 */
      logX2[curpos] = LOGP( logM[frompos] , logX2[frompos] );

      /* Update for states which emit Y only */
      /***************************************/

      frompos = cur*cl + j-1;          /* index of the state (i,j-1) */

      /* State RY */
      aux = LOGP( - m_opening + logM[frompos] , - m_extension + logY[frompos] );
      logY[curpos] = LOGP( aux , - m_opening + logX[frompos] );

      /* State RY2 */
      aux = LOGP( logM[frompos] , logY2[frompos] );
      logY2[curpos] = LOGP( aux , logX2[frompos] );

      /* Update for states which emit X and Y */
      /****************************************/

      frompos = old*cl + j-1;          /* index of the state (i-1,j-1) */

      aux = LOGP( logX[frompos] , logY[frompos] );
      aux2 = LOGP( 0 , logM[frompos] );
      logM[curpos] = LOGP( aux , aux2 ) + scaled_blosum[ BINDEX( aaX[i-1] , aaY[j-1] ) ];
      
      /*      printf("i=%d , j=%d\nM=%.5f\nX=%.5f\nY=%.5f\nX2=%.5f\nY2=%.5f\n",i,j,logM[curpos],logX[curpos],logY[curpos],logX2[curpos],logY2[curpos]);
       */

    }  /* end of j=1:nY loop */


    /* Update the culumn order */
    cur = 1-cur;
    old = 1-old;

  }  /* end of j=1:nX loop */


  /* Termination */
  /***************/

  curpos = old*cl + nY;                /* index of the state (nX,nY) */
  aux = LOGP( logX2[curpos] , logY2[curpos] );
  aux2 = LOGP( 0 , logM[curpos] );
  /*  kernel_value = LOGP( aux , aux2 );*/

  /* Memory release */
    SG_FREE(logM);
    SG_FREE(logX);
    SG_FREE(logY);
    SG_FREE(logX2);
    SG_FREE(logY2);

  /* Return the logarithm of the kernel */
  return (float32_t)LOGP(aux,aux2)/INTSCALE;
}

/********************/
/* Public functions */
/********************/


/* Return the log-probability of two sequences x and y under a pair HMM model */
/* x and y are strings of aminoacid letters, e.g., "AABRS" */
float64_t CLocalAlignmentStringKernel::compute(int32_t idx_x, int32_t idx_y)
{
  int32_t *aax,*aay;  /* to convert x and y into sequences of amino-acid indexes */
  int32_t lx=0,ly=0;       /* lengths of x and y */
  int32_t i,j;

  bool free_x, free_y;
  char* x=((CStringFeatures<char>*) lhs)->get_feature_vector(idx_x, lx, free_x);
  char* y=((CStringFeatures<char>*) rhs)->get_feature_vector(idx_y, ly, free_y);
  ASSERT(x && y);

  if ((lx<1) || (ly<1))
    SG_ERROR("empty chain");

  /* Create aax and aay */

  if ((aax=(int32_t *)calloc(lx,sizeof(int32_t))) == NULL)
    SG_ERROR("run out of memory");
  if ((aay=(int32_t *)calloc(ly,sizeof(int32_t))) == NULL)
    SG_ERROR("run out of memory");

  /* Extract the characters corresponding to aminoacids and keep their indexes */

  j=0;
  for (i=0 ; i<lx ; i++) 
    if (isAA[toupper(x[i])])
      aax[j++] = aaIndex[toupper(x[i])-'A'];
  lx = j;
  j=0;
  for (i=0 ; i<ly ; i++)
    if (isAA[toupper(y[i])])
      aay[j++] = aaIndex[toupper(y[i])-'A'];
  ly = j;


  /* Compute the pair HMM score */
  float64_t result=LAkernelcompute(aax,aay,lx,ly);

  /* Release memory */
  SG_FREE(aax);
  SG_FREE(aay);

  ((CStringFeatures<char>*) lhs)->free_feature_vector(x, idx_x, free_x);
  ((CStringFeatures<char>*) rhs)->free_feature_vector(y, idx_y, free_y);

  return result;
}

void CLocalAlignmentStringKernel::init()
{
    initialized = false;
    isAA = NULL;
    aaIndex = NULL;

    m_opening = 10;
    m_extension = 2;

    scaled_blosum=SG_MALLOC(int32_t, sizeof(blosum));
    init_logsum();

    m_parameters->add(&initialized, "initialized", "if kernel is initalized");
    m_parameters->add(&m_opening, "opening", "opening gap opening penalty");
    m_parameters->add(&m_extension, "extension", "extension gap extension penalty");
}