1 | #include <stdio.h> |
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2 | #include <ctype.h> |
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3 | #include <stdlib.h> |
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4 | #include <string.h> |
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5 | #include "clustalw.h" |
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6 | |
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7 | |
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8 | /* |
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9 | * Prototypes |
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10 | */ |
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11 | void calc_p_penalties(char **aln, sint n, sint fs, sint ls, sint *weight); |
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12 | void calc_h_penalties(char **aln, sint n, sint fs, sint ls, sint *weight); |
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13 | void calc_v_penalties(char **aln, sint n, sint fs, sint *weight); |
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14 | sint local_penalty(sint penalty, sint n, sint *pweight, sint *hweight, sint *vweight); |
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15 | float percentid(char *s1, char *s2,sint length); |
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16 | /* |
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17 | * Global variables |
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18 | */ |
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19 | |
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20 | extern sint gap_dist; |
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21 | extern sint max_aa; |
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22 | extern sint debug; |
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23 | extern Boolean dnaflag; |
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24 | extern Boolean use_endgaps; |
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25 | extern Boolean endgappenalties; |
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26 | extern Boolean no_var_penalties, no_hyd_penalties, no_pref_penalties; |
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27 | extern char hyd_residues[]; |
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28 | extern char *amino_acid_codes; |
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29 | |
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30 | /* vwindow is the number of residues used for a window for the variable zone penalties */ |
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31 | /* vll is the lower limit for the variable zone penalties (vll < pen < 1.0) */ |
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32 | int vll=50; |
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33 | int vwindow=5; |
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34 | |
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35 | sint vlut[26][26] = { |
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36 | /* A B C D E F G H I J K L M N O P Q R S T U V W X Y Z */ |
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37 | /*A*/ 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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38 | /*B*/ 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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39 | /*C*/ 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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40 | /*D*/ 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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41 | /*E*/ 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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42 | /*F*/ 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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43 | /*G*/ 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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44 | /*H*/ 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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45 | /*I*/ 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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46 | /*J*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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47 | /*K*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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48 | /*L*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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49 | /*M*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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50 | /*N*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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51 | /*O*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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52 | /*P*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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53 | /*Q*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, |
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54 | /*R*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, |
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55 | /*S*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, |
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56 | /*T*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, |
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57 | /*U*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, |
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58 | /*V*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, |
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59 | /*W*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, |
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60 | /*X*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, |
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61 | /*Y*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, |
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62 | /*Z*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1 |
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63 | }; |
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64 | |
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65 | /* pascarella probabilities for opening a gap at specific residues */ |
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66 | char pr[] = {'A' , 'C', 'D', 'E', 'F', 'G', 'H', 'K', 'I', 'L', |
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67 | 'M' , 'N', 'P', 'Q', 'R', 'S', 'T', 'V', 'Y', 'W'}; |
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68 | sint pas_op[] = { 87, 87,104, 69, 80,139,100,104, 68, 79, |
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69 | 71,137,126, 93,128,124,111, 75,100, 77}; |
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70 | sint pas_op2[] ={ 88, 57,111, 98, 75,126, 95, 97, 70, 90, |
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71 | 60,122,110,107, 91,125,124, 81,106, 88}; |
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72 | sint pal_op[] = { 84, 69,128, 78, 88,176, 53, 95, 55, 49, |
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73 | 52,148,147,100, 91,129,105, 51,128, 88}; |
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74 | |
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75 | float reduced_gap = 1.0; |
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76 | Boolean nvar_pen,nhyd_pen,npref_pen; /* local copies of ho_hyd_penalties, no_pref_penalties */ |
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77 | sint gdist; /* local copy of gap_dist */ |
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78 | |
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79 | void calc_gap_coeff(char **alignment, sint *gaps, sint **profile, Boolean struct_penalties, |
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80 | char *gap_penalty_mask, sint first_seq, sint last_seq, |
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81 | sint prf_length, sint gapcoef, sint lencoef) |
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82 | { |
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83 | |
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84 | char c; |
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85 | sint i, j; |
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86 | sint is, ie; |
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87 | static sint numseq,val,pcid; |
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88 | static sint *gap_pos; |
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89 | static sint *v_weight, *p_weight, *h_weight; |
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90 | static float scale; |
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91 | |
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92 | numseq = last_seq - first_seq; |
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93 | if(numseq == 2) |
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94 | { |
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95 | pcid=percentid(alignment[first_seq],alignment[first_seq+1],prf_length); |
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96 | } |
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97 | else pcid=0; |
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98 | |
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99 | for (j=0; j<prf_length; j++) |
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100 | gaps[j] = 0; |
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101 | /* |
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102 | Check for a gap penalty mask |
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103 | */ |
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104 | if (struct_penalties != NONE) |
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105 | { |
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106 | nvar_pen = nhyd_pen = npref_pen = TRUE; |
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107 | gdist = 0; |
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108 | } |
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109 | else if (no_var_penalties == FALSE && pcid > 60) |
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110 | { |
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111 | if(debug>0) fprintf(stderr,"Using variable zones to set gap penalties (pcid = %d)\n",pcid); |
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112 | nhyd_pen = npref_pen = TRUE; |
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113 | nvar_pen = FALSE; |
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114 | } |
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115 | else |
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116 | { |
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117 | nvar_pen = TRUE; |
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118 | nhyd_pen = no_hyd_penalties; |
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119 | npref_pen = no_pref_penalties; |
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120 | gdist = gap_dist; |
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121 | } |
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122 | |
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123 | for (i=first_seq; i<last_seq; i++) |
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124 | { |
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125 | /* |
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126 | Include end gaps as gaps ? |
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127 | */ |
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128 | is = 0; |
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129 | ie = prf_length; |
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130 | if (use_endgaps == FALSE && endgappenalties==FALSE) |
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131 | { |
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132 | for (j=0; j<prf_length; j++) |
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133 | { |
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134 | c = alignment[i][j]; |
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135 | if ((c < 0) || (c > max_aa)) |
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136 | is++; |
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137 | else |
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138 | break; |
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139 | } |
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140 | for (j=prf_length-1; j>=0; j--) |
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141 | { |
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142 | c = alignment[i][j]; |
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143 | if ((c < 0) || (c > max_aa)) |
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144 | ie--; |
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145 | else |
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146 | break; |
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147 | } |
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148 | } |
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149 | |
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150 | for (j=is; j<ie; j++) |
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151 | { |
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152 | if ((alignment[i][j] < 0) || (alignment[i][j] > max_aa)) |
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153 | gaps[j]++; |
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154 | } |
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155 | } |
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156 | |
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157 | if ((!dnaflag) && (nvar_pen == FALSE)) |
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158 | { |
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159 | v_weight = (sint *) ckalloc( (prf_length+2) * sizeof (sint) ); |
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160 | calc_v_penalties(alignment, prf_length, first_seq, v_weight); |
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161 | } |
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162 | |
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163 | |
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164 | if ((!dnaflag) && (npref_pen == FALSE)) |
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165 | { |
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166 | p_weight = (sint *) ckalloc( (prf_length+2) * sizeof (sint) ); |
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167 | calc_p_penalties(alignment, prf_length, first_seq, last_seq, p_weight); |
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168 | } |
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169 | |
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170 | if ((!dnaflag) && (nhyd_pen == FALSE)) |
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171 | { |
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172 | h_weight = (sint *) ckalloc( (prf_length+2) * sizeof (sint) ); |
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173 | calc_h_penalties(alignment, prf_length, first_seq, last_seq, h_weight); |
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174 | } |
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175 | |
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176 | gap_pos = (sint *) ckalloc( (prf_length+2) * sizeof (sint) ); |
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177 | /* |
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178 | mark the residues close to an existing gap (set gaps[i] = -ve) |
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179 | */ |
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180 | if (dnaflag || (gdist <= 0)) |
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181 | { |
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182 | for (i=0;i<prf_length;i++) gap_pos[i] = gaps[i]; |
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183 | } |
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184 | else |
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185 | { |
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186 | i=0; |
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187 | while (i<prf_length) |
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188 | { |
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189 | if (gaps[i] <= 0) |
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190 | { |
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191 | gap_pos[i] = gaps[i]; |
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192 | i++; |
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193 | } |
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194 | else |
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195 | { |
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196 | for (j = -gdist+1; j<0; j++) |
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197 | { |
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198 | if ((i+j>=0) && (i+j<prf_length) && |
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199 | ((gaps[i+j] == 0) || (gaps[i+j] < j))) gap_pos[i+j] = j; |
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200 | } |
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201 | while (gaps[i] > 0) |
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202 | { |
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203 | if (i>=prf_length) break; |
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204 | gap_pos[i] = gaps[i]; |
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205 | i++; |
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206 | } |
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207 | for (j = 0; j<gdist; j++) |
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208 | { |
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209 | if (gaps[i+j] > 0) break; |
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210 | if ((i+j>=0) && (i+j<prf_length) && |
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211 | ((gaps[i+j] == 0) || (gaps[i+j] < -j))) gap_pos[i+j] = -j-1; |
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212 | } |
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213 | i += j; |
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214 | } |
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215 | } |
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216 | } |
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217 | if (debug>1) |
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218 | { |
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219 | fprintf(stdout,"gap open %d gap ext %d\n",(pint)gapcoef,(pint)lencoef); |
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220 | fprintf(stdout,"gaps:\n"); |
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221 | for(i=0;i<prf_length;i++) fprintf(stdout,"%d ", (pint)gaps[i]); |
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222 | fprintf(stdout,"\n"); |
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223 | fprintf(stdout,"gap_pos:\n"); |
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224 | for(i=0;i<prf_length;i++) fprintf(stdout,"%d ", (pint)gap_pos[i]); |
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225 | fprintf(stdout,"\n"); |
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226 | } |
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227 | |
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228 | |
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229 | for (j=0;j<prf_length; j++) |
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230 | { |
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231 | |
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232 | if (gap_pos[j] <= 0) |
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233 | { |
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234 | /* |
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235 | apply residue-specific and hydrophilic gap penalties. |
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236 | */ |
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237 | if (!dnaflag) { |
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238 | profile[j+1][GAPCOL] = local_penalty(gapcoef, j, |
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239 | p_weight, h_weight, v_weight); |
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240 | profile[j+1][LENCOL] = lencoef; |
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241 | } |
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242 | else { |
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243 | profile[j+1][GAPCOL] = gapcoef; |
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244 | profile[j+1][LENCOL] = lencoef; |
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245 | } |
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246 | |
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247 | /* |
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248 | increase gap penalty near to existing gaps. |
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249 | */ |
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250 | if (gap_pos[j] < 0) |
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251 | { |
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252 | profile[j+1][GAPCOL] *= 2.0+2.0*(gdist+gap_pos[j])/gdist; |
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253 | } |
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254 | |
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255 | |
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256 | } |
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257 | else |
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258 | { |
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259 | scale = ((float)(numseq-gaps[j])/(float)numseq) * reduced_gap; |
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260 | profile[j+1][GAPCOL] = scale*gapcoef; |
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261 | profile[j+1][LENCOL] = 0.5 * lencoef; |
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262 | } |
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263 | /* |
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264 | apply the gap penalty mask |
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265 | */ |
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266 | if (struct_penalties != NONE) |
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267 | { |
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268 | val = gap_penalty_mask[j]-'0'; |
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269 | if (val > 0 && val < 10) |
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270 | { |
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271 | profile[j+1][GAPCOL] *= val; |
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272 | profile[j+1][LENCOL] *= val; |
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273 | } |
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274 | } |
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275 | /* |
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276 | make sure no penalty is zero - even for all-gap positions |
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277 | */ |
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278 | if (profile[j+1][GAPCOL] <= 0) profile[j+1][GAPCOL] = 1; |
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279 | if (profile[j+1][LENCOL] <= 0) profile[j+1][LENCOL] = 1; |
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280 | } |
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281 | |
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282 | /* set the penalties at the beginning and end of the profile */ |
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283 | if(endgappenalties==TRUE) |
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284 | { |
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285 | profile[0][GAPCOL] = gapcoef; |
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286 | profile[0][LENCOL] = lencoef; |
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287 | } |
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288 | else |
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289 | { |
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290 | profile[0][GAPCOL] = 0; |
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291 | profile[0][LENCOL] = 0; |
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292 | profile[prf_length][GAPCOL] = 0; |
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293 | profile[prf_length][LENCOL] = 0; |
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294 | } |
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295 | if (debug>0) |
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296 | { |
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297 | fprintf(stdout,"Opening penalties:\n"); |
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298 | for(i=0;i<=prf_length;i++) fprintf(stdout," %d:%d ",i, (pint)profile[i][GAPCOL]); |
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299 | fprintf(stdout,"\n"); |
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300 | } |
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301 | if (debug>0) |
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302 | { |
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303 | fprintf(stdout,"Extension penalties:\n"); |
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304 | for(i=0;i<=prf_length;i++) fprintf(stdout,"%d:%d ",i, (pint)profile[i][LENCOL]); |
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305 | fprintf(stdout,"\n"); |
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306 | } |
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307 | if ((!dnaflag) && (nvar_pen == FALSE)) |
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308 | v_weight=ckfree((void *)v_weight); |
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309 | |
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310 | if ((!dnaflag) && (npref_pen == FALSE)) |
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311 | p_weight=ckfree((void *)p_weight); |
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312 | |
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313 | if ((!dnaflag) && (nhyd_pen == FALSE)) |
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314 | h_weight=ckfree((void *)h_weight); |
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315 | |
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316 | |
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317 | gap_pos=ckfree((void *)gap_pos); |
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318 | } |
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319 | |
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320 | void calc_v_penalties(char **aln, sint n, sint fs, sint *weight) |
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321 | { |
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322 | char ix1,ix2; |
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323 | sint i,j,t; |
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324 | |
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325 | for (i=0;i<n;i++) |
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326 | { |
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327 | weight[i] = 0; |
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328 | t=0; |
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329 | for(j=i-vwindow;j<i+vwindow;j++) |
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330 | { |
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331 | if(j>=0 && j<n) |
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332 | { |
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333 | ix1 = aln[fs][j]; |
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334 | ix2 = aln[fs+1][j]; |
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335 | if ((ix1 < 0) || (ix1 > max_aa) || (ix2< 0) || (ix2> max_aa)) continue; |
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336 | weight[i] += vlut[amino_acid_codes[ix1]-'A'][amino_acid_codes[ix2]-'A']; |
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337 | t++; |
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338 | } |
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339 | } |
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340 | /* now we have a weight -t < w < t */ |
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341 | weight[i] +=t; |
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342 | if(t>0) |
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343 | weight[i] = (weight[i]*100)/(2*t); |
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344 | else |
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345 | weight[i] = 100; |
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346 | /* now we have a weight vll < w < 100 */ |
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347 | if (weight[i]<vll) weight[i]=vll; |
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348 | } |
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349 | |
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350 | |
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351 | } |
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352 | |
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353 | void calc_p_penalties(char **aln, sint n, sint fs, sint ls, sint *weight) |
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354 | { |
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355 | char ix; |
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356 | sint j,k,numseq; |
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357 | sint i; |
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358 | |
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359 | numseq = ls - fs; |
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360 | for (i=0;i<n;i++) |
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361 | { |
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362 | weight[i] = 0; |
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363 | for (k=fs;k<ls;k++) |
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364 | { |
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365 | for (j=0;j<22;j++) |
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366 | { |
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367 | ix = aln[k][i]; |
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368 | if ((ix < 0) || (ix > max_aa)) continue; |
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369 | if (amino_acid_codes[ix] == pr[j]) |
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370 | { |
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371 | weight[i] += (180-pas_op[j]); |
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372 | break; |
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373 | } |
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374 | } |
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375 | } |
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376 | weight[i] /= numseq; |
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377 | } |
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378 | |
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379 | } |
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380 | |
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381 | void calc_h_penalties(char **aln, sint n, sint fs, sint ls, sint *weight) |
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382 | { |
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383 | |
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384 | /* |
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385 | weight[] is the length of the hydrophilic run of residues. |
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386 | */ |
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387 | char ix; |
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388 | sint nh,j,k; |
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389 | sint i,e,s; |
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390 | sint *hyd; |
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391 | float scale; |
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392 | |
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393 | hyd = (sint *)ckalloc((n+2) * sizeof(sint)); |
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394 | nh = (sint)strlen(hyd_residues); |
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395 | for (i=0;i<n;i++) |
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396 | weight[i] = 0; |
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397 | |
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398 | for (k=fs;k<ls;k++) |
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399 | { |
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400 | for (i=0;i<n;i++) |
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401 | { |
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402 | hyd[i] = 0; |
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403 | for (j=0;j<nh;j++) |
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404 | { |
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405 | ix = aln[k][i]; |
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406 | if ((ix < 0) || (ix > max_aa)) continue; |
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407 | if (amino_acid_codes[ix] == hyd_residues[j]) |
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408 | { |
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409 | hyd[i] = 1; |
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410 | break; |
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411 | } |
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412 | } |
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413 | } |
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414 | i = 0; |
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415 | while (i < n) |
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416 | { |
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417 | if (hyd[i] == 0) i++; |
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418 | else |
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419 | { |
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420 | s = i; |
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421 | while ((hyd[i] != 0) && (i<n)) i++; |
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422 | e = i; |
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423 | if (e-s > 3) |
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424 | for (j=s; j<e; j++) weight[j] += 100; |
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425 | } |
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426 | } |
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427 | } |
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428 | |
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429 | scale = ls - fs; |
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430 | for (i=0;i<n;i++) |
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431 | weight[i] /= scale; |
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432 | |
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433 | hyd=ckfree((void *)hyd); |
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434 | |
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435 | if (debug>1) |
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436 | { |
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437 | for(i=0;i<n;i++) fprintf(stdout,"%d ", (pint)weight[i]); |
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438 | fprintf(stdout,"\n"); |
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439 | } |
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440 | |
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441 | } |
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442 | |
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443 | sint local_penalty(sint penalty, sint n, sint *pweight, sint *hweight, sint *vweight) |
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444 | { |
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445 | |
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446 | Boolean h = FALSE; |
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447 | float gw; |
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448 | |
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449 | if (dnaflag) return(1); |
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450 | |
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451 | gw = 1.0; |
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452 | if (nvar_pen == FALSE) |
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453 | { |
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454 | gw *= (float)vweight[n]/100.0; |
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455 | } |
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456 | |
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457 | if (nhyd_pen == FALSE) |
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458 | { |
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459 | if (hweight[n] > 0) |
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460 | { |
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461 | gw *= 0.5; |
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462 | h = TRUE; |
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463 | } |
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464 | } |
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465 | if ((npref_pen == FALSE) && (h==FALSE)) |
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466 | { |
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467 | gw *= ((float)pweight[n]/100.0); |
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468 | } |
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469 | |
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470 | gw *= penalty; |
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471 | return((sint)gw); |
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472 | |
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473 | } |
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474 | |
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475 | float percentid(char *s1, char *s2,sint length) |
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476 | { |
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477 | sint i; |
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478 | sint count,total; |
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479 | float score; |
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480 | |
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481 | count = total = 0; |
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482 | for (i=0;i<length;i++) { |
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483 | if ((s1[i]>=0) && (s1[i]<max_aa)) { |
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484 | total++; |
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485 | if (s1[i] == s2[i]) count++; |
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486 | } |
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487 | if (s1[i]==(-3) || s2[i]==(-3)) break; |
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488 | |
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489 | } |
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490 | |
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491 | if(total==0) score=0; |
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492 | else |
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493 | score = 100.0 * (float)count / (float)total; |
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494 | return(score); |
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495 | |
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496 | } |
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497 | |
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