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package var;
import java.io.Serializable;
import java.lang.reflect.Array;
import java.util.ArrayList;
import java.util.Arrays;
import java.util.HashMap;
import java.util.HashSet;
import java.util.Set;
import dna.Data;
import dna.Gene;
import dna.GeneSet;
import driver.Search;
import shared.Shared;
import shared.Tools;
import structures.Range;
public class Variation implements Comparable<Variation>, Serializable, Cloneable {
// >locus ploidy haplotype chromosome begin end varType reference alleleSeq totalScore hapLink xRef
/**
*
*/
private static final long serialVersionUID = -3847258470952802740l;
public Variation(VarLine line){
// this(line.chromosome, line.beginLoc, line.endLoc, line.xRef, line.varType, line.ref, line.call);
this(line.chromosome, line.beginLoc, line.endLoc, line.varType, line.ref, line.call);
assert(!((varType==INS || varType==DELINS || varType==SNP) && call==null)) : "\n"+line+"\n"+this+
"\nline.ref="+line.ref+"\nline.call="+line.call+"\nref="+ref+"\ncall="+call;
assert(beginLoc<=endLoc) : line.toString();
assert(this.equals(line)) : "\n\n"+this+"\n!=\n"+line;
assert(line.equals(this)) : "\n\n"+this+"\n!=\n"+line;
// if(xRef==11429487){
// System.out.println("\n"+this.toString());
// }
}
// public Variation(GeneVarLine line){
//// this(line.chromosome, line.beginLoc, line.endLoc, line.xRef, line.varType, line.ref, line.call);
// this(line.chromosome, line.beginLoc, line.endLoc, line.xRef, line.xRefArray, line.varType, line.ref, line.call);
//
// assert(beginLoc<=endLoc) : line.toString();
//
// assert(this.equals(line)) : "\n\n"+this+"\n!=\n"+line.toSuperString()+"\n\n"+line;
// assert(line.equals(this)) : "\n\n"+this+"\n!=\n"+line.toSuperString()+"\n\n"+line;
//
// }
public Variation(Variation line){
this(line.chromosome, line.beginLoc, line.endLoc, line.varType, line.ref, line.call);
assert(beginLoc<=endLoc) : line.toString();
assert(this.equals(line)) : "\n\n"+this+"\n!=\n"+line.toSuperString()+"\n\n"+line;
assert(line.equals(this)) : "\n\n"+this+"\n!=\n"+line.toSuperString()+"\n\n"+line;
}
public Variation(int chr, int bLoc, int eLoc, byte vType, String rf, String ca){
chromosome=chr;
beginLoc=bLoc;
endLoc=eLoc;
varType=vType;
setDetails(vType, rf, ca);
assert(beginLoc<=endLoc) : toString();
}
public Variation(){}
@Override
public Variation clone(){
Variation v=null;
try {
v=(Variation) super.clone();
} catch (CloneNotSupportedException e) {
// TODO Auto-generated catch block
e.printStackTrace();
}
return v;
}
public static final HashSet<Variation> toVariations(VarLine[] array, boolean retainEqual){
HashSet<Variation> set=new HashSet<Variation>(array.length);
for(VarLine line : array){
Variation var=new Variation(line);
if(retainEqual || var.varType!=Variation.REF){
if(!set.contains(var)){
set.add(var);
}
}
}
return set;
}
public static final Variation[] toVariationArray(VarLine[][] array, boolean retainEqual){
HashSet<Variation> set=toVariations(array[0], retainEqual);
for(int i=1; i<array.length; i++){
set.addAll(toVariations(array[i], retainEqual));
}
Variation[] vars=set.toArray(new Variation[set.size()]);
Arrays.sort(vars);
return vars;
}
public static final Variation[] toVariationArray(VarLine[] array, boolean retainEqual){
HashSet<Variation> set=toVariations(array, retainEqual);
Variation[] vars=set.toArray(new Variation[set.size()]);
Arrays.sort(vars);
return vars;
}
@SuppressWarnings("unchecked")
public static final <X extends Comparable<? super X>> X[] toArray(Class<X> c, Set<X> set){
set.getClass().getTypeParameters();
X[] array=(X[])Array.newInstance(c,set.size());
array=set.toArray(array);
int i=0;
for(X x : set){
array[i]=x;
i++;
}
Arrays.sort(array);
return array;
}
public static VarLine[] filterCodingVariances(VarLine[] variances, int chrom, boolean nearby){
Range[] ranges=(nearby ? Data.geneNearbyRangeMatrix(chrom) : Data.geneCodeAndExonRangeMatrix(chrom));
ArrayList<VarLine> list=new ArrayList<VarLine>(8+variances.length/8);
for(VarLine var : variances){
if(var.varType!=VarLine.REF && var.varType!=VarLine.NOREF){
int loc=var.beginLoc;
int rnum=Search.findPointBinary(loc, ranges);
if(ranges[rnum].intersects(var.beginLoc, var.endLoc)){
list.add(var);
}
for(int i=rnum; i<ranges.length; i++){
Range r=ranges[i];
if(r.a>var.endLoc){break;} //Out of range
if(r.intersects(var.beginLoc, var.endLoc)){
list.add(var);
break;
}
}
}
}
return list.toArray(new VarLine[list.size()]);
}
/**
* Generates an array of non-overlapping Ranges, sorted by index, ascending.
* To each is attached a list of all overlapping Variations from the input array.
* @param va
* @return The array of ranges
*/
public static Range[] makeVarRanges(Variation[] va){
// System.out.println("va.length="+va.length);
if(va==null || va.length==0){
return new Range[0];
}
ArrayList<Range> ra=new ArrayList<Range>(va.length);
for(Variation v : va){
Range r=new Range(v.beginLoc, v.endLoc);
r.obj1=new ArrayList<Variation>();
((ArrayList<Variation>)r.obj1).add(v);
ra.add(r);
}
Shared.sort(ra);
ArrayList<Range> ra2=new ArrayList<Range>(va.length);
Range current=null;
// System.out.println("ra.size="+ra.size());
for(Range r : ra){
// System.out.println("\ncurrent="+current+", r="+r);
if(current==null){current=r;}
else if(current.intersects(r)){
// System.out.println("merged");
Range temp=current.merge(r);
temp.obj1=current.obj1;
((ArrayList<Variation>)temp.obj1).addAll((ArrayList<Variation>)r.obj1);
current=temp;
}else{
// System.out.println("added");
ra2.add(current);
current=r;
}
// System.out.println("current="+current+", r="+r);
}
// System.out.println("\ncurrent="+current);
// System.out.println("ra2.size="+ra2.size());
assert(current!=null); //Note: this could be null if input was empty, I guess...
assert(ra2.size()==0 || ra2.get(ra2.size()-1)!=current);
ra2.add(current);
return ra2.toArray(new Range[ra2.size()]);
}
public static final int toRsid(String s){return xRefToId(s);}
public static final int xRefToId(String s){
// System.out.println(s);
if(s==null || s.length()==0){return -1;}
// assert(s.startsWith("dbsnp:rs")) : s;
if(s.contains(":")){
s=s.substring(s.indexOf(':')+1);
}
int i=0, max=s.length();
// System.err.println(s);
while(i<max && !Tools.isDigit(s.charAt(i))){i++;}
if(i>=max){assert(s.equals(".")) : s; return -1;}
s=s.substring(i);
return Integer.parseInt(s);
}
public static final int[] toRsidArray(String s){return xRefToIdArray(s);}
public static final int[] xRefToIdArray(String s){
if(s==null || s.length()<1){return null;}
String[] array=s.split("[,;]");
int[] r=new int[array.length];
for(int i=0; i<array.length; i++){
r[i]=xRefToId(array[i]);
if(r[i]==-1){
if(r.length==1){return null;}
//This can be safely disabled. But it is best to fix this case by making the array smaller.
assert(false) : "Not a real rsID: "+s;
}
}
return r;
}
public boolean matches(Variation line){
if(line==null || chromosome!=line.chromosome || beginLoc!=line.beginLoc || endLoc!=line.endLoc || varType!=line.varType){
return false;
}
return matches(line.varType, line.ref, line.call);
}
// public boolean matchesLoose(VarLine line){
// if(line==null || chromosome!=line.chromosome || !intersects(line)){
// return false;
// }
// if(isEqual() && line.isEqual()){return true;}
// if(varType!=line.varType){return false;}
// return matches(line.varType, line.ref, line.call);
// }
/** Overlap and don't contradict each other */
public boolean matchesLoose(VarLine line){
if(line==null || chromosome!=line.chromosome || !intersects(line)){
return false;
}
if(isTrueVariation()){
if(varType!=line.varType){return false;}
return matches(line.varType, line.ref, line.call);
}else if(isRef()){
return line.isRef();
}else{
assert(isUnsureVariation()) : this;
return line.isUnsureVariation();
}
}
private boolean matches(int type, String ref2, String call2){
if(type==REF || type==REFPOINT || type==DEL || type==NOCALL){
return true;
}
return call.equals(call2);
}
private void setDetails(byte vt, String rf, String ca){
ref=null;
call=null;
switch(vt){
case REF: {
}break;
case SNP: {
ref=rf; call=ca;
}break;
case INS: {
call=ca;
}break;
case DEL: {
ref=rf;
}break;
case DELINS: {
ref=rf; call=ca;
}break;
case REFCON: {
ref=rf; call=ca;
}break;
case REFINCON: {
ref=rf; call=ca;
}break;
case NOCALL: {
//I can't remember if nocalls need N or null calls
// ref=rf;
// call=ca;
// assert(ref!=null && call!=null && ref.length()==call.length()) : ref+", "+call;
}break;
case NOREF: {
//I can't remember if norefs need N or null refs
// ref=rf;
call=ca;
// assert(ref!=null && call!=null && ref.length()==call.length()) : ref+", "+call;
}break;
case PAR: {
ref=rf; call=ca;
}break;
case NULL: {
ref=rf; call=ca;
}break;
case REFPOINT: {
ref=call=null;
}break;
default: {assert(false);}
}
intern();
}
public String locationString(){
return locationString(0);
}
public String locationString(int base){
assert(base==0 || base==1);
if(beginLoc==endLoc){
return "("+(beginLoc+base)+")";
}
return "("+(beginLoc+base)+" - "+(endLoc+base)+")";
// if(beginLoc==endLoc){
// return (beginLoc+base)+"";
// }
// return (beginLoc+base)+"-"+(endLoc+base);
}
public String toSuperString(){return toString();}
@Override
public String toString(){
return toString(0);
}
public String toString(int base){
StringBuilder sb=new StringBuilder();
sb.append("chr"+Gene.chromCodes[chromosome]);
while(sb.length()<5){sb.append(' ');}
sb.append('\t');
sb.append(locationString(base)+"\t");
sb.append(varTypeMap[varType]);
sb.append("\t"+(ref==null ? "" : ref));
sb.append("\t"+(call==null ? "" : call));
sb.append('\t');
return sb.toString();
}
public String toSourceString(){
StringBuilder sb=new StringBuilder(64);
sb.append("chr"+Gene.chromCodes[chromosome]+"\t");
sb.append(beginLoc+"\t");
if(varType==INS){
sb.append(beginLoc+"\t");
}else{
sb.append((endLoc+1)+"\t");
}
sb.append(varTypeMap[varType]+"\t");
sb.append((ref==null ? "" : ref)+"\t");
sb.append((call==null ? "" : call)+"\t");
return sb.toString();
}
public static String header(){
return "chrom\tstart\tstop\ttype\tref\tcall\trsID";
}
public String toShortString(){
StringBuilder sb=new StringBuilder();
sb.append(locationString()+"\t");
sb.append(varTypeMap[varType]);
if(ref!=null){sb.append("\t"+ref);}
if(call!=null){sb.append("\t"+call);}
return sb.toString();
}
public static final int find(String a, String[] array){
for(int i=0; i<array.length; i++){
if(a.equals(array[i])){return i;}
}
assert(false) : "Can't find "+a+" in "+Arrays.toString(array);
return -1;
}
public final int lengthRef(){
switch(varType){
case SNP: {
assert(endLoc-beginLoc+1==1) : "\n"+endLoc+"-"+beginLoc+"+1 = "+(endLoc-beginLoc+1)+" != "+1+"\n"+this.toString()+"\n";
assert(call!=null && call.length()==1) : "\ncall= '"+call+"'\n"+this.toString();
return 1;
}
case INS: {
return 0;
}
case REFPOINT: {
return 0;
}
// case NOREF: {
// throw new RuntimeException();
// }
// case NULL: {
// throw new RuntimeException();
// }
default: {
break;
}
}
return endLoc-beginLoc+1;
}
public final int lengthMax(){return max(lengthRef(), lengthVar());}
public final int lengthMin(){return min(lengthRef(), lengthVar());}
public final int lengthDif(){return isNR_or_NC() ? 0 : lengthVar()-lengthRef();}
public final int lengthVar(){
switch(varType){
case REF: {
return endLoc-beginLoc+1;
}
case SNP: {
assert(endLoc-beginLoc+1==1);
assert(call!=null && call.length()==1);
return 1;
}
case INS: {
assert(call!=null);
return call.length();
}
case REFPOINT: {
return 0;
}
case DEL: {
assert(call==null);
return 0;
}
case DELINS: {
assert(call!=null);
return call.length();
}
case REFCON: {
return endLoc-beginLoc+1;
}
case REFINCON: {
assert(false) : "Warning - Length cannot be known for certain.";
return endLoc-beginLoc+1;
}
case NOCALL: {
assert(false) : "Warning - Length cannot be known for certain.";
return endLoc-beginLoc+1;
}
case NOREF: {
assert(false) : "Warning - Length cannot be known for certain.";
return endLoc-beginLoc+1;
}
case PAR: {
assert(call!=null);
return call.length();
}
case NULL: {
assert(false);
throw new RuntimeException();
}
default: {throw new RuntimeException();}
}
}
// //TODO Note that this may be wrong for e.g. insertions, deletions, and if/when changed to half-open numbering.
// public final int length(){
// if(varType==INS){return 0;}
// return endLoc-beginLoc+1;
// }
// public final int length2(){
// if(varType==INS){return call==null ? 0 : call.length();}
// if(varType==DELINS){return call==null ? (endLoc-beginLoc+1) : max(call.length(), endLoc-beginLoc+1);}
// return endLoc-beginLoc+1;
// }
public final boolean isPoint(){
return varType==INS || varType==REFPOINT;
}
public final boolean isRef(){
return varType==REF || varType==REFPOINT;
}
public final boolean isTrueVariation(){
return varType==SNP || varType==INS || varType==DEL || varType==DELINS;
}
public final boolean isNoCall(){
return varType==NOCALL || varType==REFCON || varType==REFINCON;
}
public final boolean isNR_or_NC(){
return varType==NOCALL || varType==NOREF || varType==REFCON || varType==REFINCON;
}
public final boolean isUnsureVariation(){
return varType==NOCALL || varType==NOREF || varType==REFINCON || varType==REFCON;
}
// /** TODO May be slow. Perhaps add a boolean field. */
// public boolean isCoding(){
// int middle=((beginLoc+endLoc)/2);
// GeneSet[] sets=Data.getNearestGeneSets(chromosome, middle);
// for(GeneSet gs : sets){
// for(Gene g : gs.genes){
// if(g.intersectsCodeAndExon(beginLoc, endLoc)){
// return true;
// }
// }
// }
// return false;
// }
/** Does this variation intersect within (range) of a coding region or splice site? */
public boolean isNearCodingOrSplice(int range, boolean includeExonsForUntranslatedGenes, boolean includeSplice){
assert(beginLoc<=endLoc);
int a=beginLoc-range, b=endLoc+range;
return isNearCodingOrSplice(range, includeExonsForUntranslatedGenes, Data.getNearestGeneSets(chromosome, a, b), includeSplice);
}
/** Does this variation intersect within (range) of a coding region or splice site? */
public boolean isNearCodingOrSplice(int range, boolean includeExonsForUntranslatedGenes){
return isNearCodingOrSplice(range, includeExonsForUntranslatedGenes, true);
}
/** Does this variation lie at least partially within an intron? */
public boolean intersectsIntron(){
assert(beginLoc<=endLoc);
int a=beginLoc, b=endLoc;
return intersectsIntron(Data.getNearestGeneSets(chromosome, a, b));
}
/** Does this variation intersect within (range) of a coding region or splice site? */
public boolean isNearCodingOrSplice(int range, boolean includeExonsForUntranslatedGenes, GeneSet[] sets, boolean includeSplice){
assert(beginLoc<=endLoc);
int a=beginLoc-range, b=endLoc+range;
// int middle=((beginLoc+endLoc)/2);
// GeneSet[] sets=Data.getNearestGeneSets(chromosome, middle);
// boolean flag=(chromosome==21 && intersects(9929078));//TODO UNDO
// if(flag){System.out.println("Found: "+Arrays.toString(sets));}
// assert(false);
if(sets==null){
assert(chromosome>=25);
return true;
}
for(GeneSet gs : sets){
// if(flag){System.out.println("### "+gs);}//TODO UNDO
for(Gene g : gs.genes){
if(!g.untranslated){
// if(flag){System.out.println("*** "+g);}//TODO UNDO
// if(flag){
// System.out.println("intersectsCodeAndExon: "+g.intersectsCodeAndExon(a, b));
// System.out.println("intersectsCode: "+g.intersectsCode(a, b));
// System.out.println("intersectsExon: "+g.intersectsExon(a, b));
// }
if(g.intersectsCodeAndExon(a, b)){
return true;
}
}else if(includeExonsForUntranslatedGenes){
// if(flag){System.out.println("*** "+g);}//TODO UNDO
//
// if(flag){
// System.out.println("intersectsExon: "+g.intersectsExon(a, b));
// }
if(g.intersectsExon(a, b)){
return true;
}
}
if(includeSplice){
int[] array=g.nearestSpliceSite(beginLoc, endLoc);
if(array[0]<=range){return true;}
}
}
}
return false;
}
/** Does this variation lie at least partially within an intron? */
public boolean intersectsIntron(GeneSet[] sets){
assert(beginLoc<=endLoc);
int a=beginLoc, b=endLoc;
// int middle=((beginLoc+endLoc)/2);
// GeneSet[] sets=Data.getNearestGeneSets(chromosome, middle);
if(sets==null){
assert(chromosome>=25);
return true;
}
for(GeneSet gs : sets){
for(Gene g : gs.genes){
if(g.intersectsIntron(a, b)){return true;}
}
}
return false;
}
public int beginLoc=-2;
public int endLoc=-2;
public int chromosome=-1;
public byte varType=-1;
public String ref=null;
public String call=null;
public static final HashMap<Object, Object> ploidyMap=makePloidyMap();
public static final String[] haploMap={"0","1","2","all"};
public static final String[] varTypeMap={"ref","snp","ins","del","sub",
"no-call-rc","no-call-ri","no-call","no-ref","PAR-called-in-X","null","refpoint"};
public static final HashMap<String, Byte> varTypeMap2=makeVarTypeMap();
private static final HashMap<String, Byte> makeVarTypeMap(){
HashMap<String, Byte> r=new HashMap<String, Byte>(32);
for(byte i=0; i<varTypeMap.length; i++){r.put(varTypeMap[i], i);}
r.put("=", REF);
r.put("ref-consistent", REFCON);
r.put("ref-inconsistent", REFINCON);
// r.put("no-call-rc", REFCON);
// r.put("no-call-ri", REFINCON);
r.put("delins", DELINS);
return r;
}
public static final byte REF=0;
public static final byte SNP=1;
public static final byte INS=2;
public static final byte DEL=3;
public static final byte DELINS=4;
public static final byte REFCON=5;
public static final byte REFINCON=6;
public static final byte NOCALL=7;
public static final byte NOREF=8;
public static final byte PAR=9;
public static final byte NULL=10;
public static final byte REFPOINT=11;
public void intern(){
// assert(false) : ref+", "+call+", "+this;
if(ref!=null){ref=Data.intern(ref);}
if(call!=null){call=Data.intern(call);}
}
private static HashMap<Object, Object> makePloidyMap(){
HashMap<Object, Object> hashy=new HashMap<Object, Object>(64);
for(int i=0; i<10; i++){
hashy.put((Byte)(byte)i, i+"");
hashy.put((Integer)i, i+"");
hashy.put(i+"", (Byte)(byte)i);
}
hashy.put((Byte)(byte)-1, "?");
hashy.put((Integer)(-1), "?");
hashy.put("?",(Byte)(byte)-1);
return hashy;
}
private static final int min(int x, int y){return x<y ? x : y;}
private static final int max(int x, int y){return x>y ? x : y;}
@Override
public final int hashCode(){
long x=chromosome;
x=x<<4;
x^=varType;
x=x<<28;
x^=beginLoc;
x=x<<16;
x^=(endLoc-beginLoc+1);
return (int)(x^(x>>>32));
}
@Override
public int compareTo(Variation other) {
if(chromosome!=other.chromosome){return other.chromosome>chromosome ? -1 : 1;}
if(beginLoc!=other.beginLoc){return other.beginLoc>beginLoc ? -1 : 1;}
if(endLoc!=other.endLoc){return other.endLoc>endLoc ? -1 : 1;}
if(varType!=other.varType){return other.varType>varType ? -1 : 1;}
if(varType==REF || varType==NOCALL){return 0;}
if(call==null){
return other.call==null ? 0 : -1;
}
return other.call==null ? 1 : call.compareTo(other.call);
}
@Override
public boolean equals(Object other){
return equals((Variation)other);
}
public boolean equals(Variation other){
return compareTo(other)==0;
}
public boolean intersects(int point){
return point>=beginLoc && point<=endLoc;
}
public boolean touches(int point){
return point>=beginLoc-1 && point<=endLoc+1;
}
/** This is quite clever. */
public static boolean overlap(int a1, int b1, int a2, int b2){
assert(a1<=b1 && a2<=b2) : a1+", "+b1+", "+a2+", "+b2;
return a2<=b1 && b2>=a1;
}
public static boolean touch(int a1, int b1, int a2, int b2){
assert(a1<=b1 && a2<=b2) : a1+", "+b1+", "+a2+", "+b2;
return a2<=(b1+1) && b2>=(a1-1);
}
/** Is (a1, b1) within (a2, b2) ? */
public static boolean isWithin(int a1, int b1, int a2, int b2){
assert(a1<=b1 && a2<=b2) : a1+", "+b1+", "+a2+", "+b2;
return a1>=a2 && b1<=b2;
}
public static boolean isWithinNotTouching(int a1, int b1, int a2, int b2){
assert(a1<=b1 && a2<=b2) : a1+", "+b1+", "+a2+", "+b2;
return a1>a2 && b1<b2;
}
//Slow if not inlined
public boolean intersects(int a2, int b2){return overlap(beginLoc, endLoc, a2, b2);}
public boolean isWithin(int a2, int b2){return isWithin(beginLoc, endLoc, a2, b2);}
public boolean isWithinNotTouching(int a2, int b2){return isWithinNotTouching(beginLoc, endLoc, a2, b2);}
public boolean intersects(Variation v){
if(v.chromosome!=chromosome){
return false;
}
int len1=lengthRef();
int len2=v.lengthRef();
if(len1<len2){
return v.intersects(this);
}
// if(v.beginLoc==46397336 || v.beginLoc==46397348){
// System.err.println(len1+": "+this+"\n"+len2+": "+v+"\n");
// }
//Now, this is at least as long (ref-wise) as v.
// if(varType==EQUAL && v.varType==INS){
// assert(false);
// }
if(!touch(beginLoc, endLoc, v.beginLoc, v.endLoc)){return false;}
// if(v.beginLoc==46397336 || v.beginLoc==46397348){
// System.err.println("Touch("+beginLoc+", "+endLoc+", "+v.beginLoc+", "+v.endLoc+")");
// }
if(v.isPoint()){
// if(v.beginLoc==46397336 || v.beginLoc==46397348){System.out.println("v");}
if(isPoint()){
// assert(beginLoc==v.beginLoc && endLoc==v.endLoc) : this+"\n"+v;
// return true;
return beginLoc==v.beginLoc;
}
// if(v.beginLoc==46397336 || v.beginLoc==46397348){System.out.println("w");}
if(this.isNoCall()){
if(len1>0){return overlap(beginLoc, endLoc, v.beginLoc, v.endLoc);} //Normal case
else{
//TODO: Bad news! Original MAY have been a length 0 no-call in half-open coordinates.
return overlap(beginLoc, endLoc+1, v.beginLoc, v.endLoc);
}
}
// if(v.beginLoc==46397336 || v.beginLoc==46397348){System.out.println("x");}
if(v.beginLoc<=beginLoc){return false;}
// if(v.beginLoc==46397336 || v.beginLoc==46397348){System.out.println("y");}
}
// if(v.beginLoc==46397336 || v.beginLoc==46397348){System.out.println("z");}
return overlap(beginLoc, endLoc, v.beginLoc, v.endLoc);
}
}
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