ALS-5981: Add gene/consequence to variant spec

data/src/main/java/edu/harvard/hms/dbmi/avillach/hpds/data/genotype/BucketIndexBySample.java

@@ -43,7 +43,7 @@ public BucketIndexBySample(VariantStore variantStore, String storageDir) throws
 
 		//Create a bucketList, containing keys for all buckets in the variantStore
 		for(String contig: contigSet){
-			FileBackedByteIndexedStorage<Integer, ConcurrentHashMap<String, VariantMasks>> contigStore = variantStore.getVariantMaskStorage().get(contig);
+			FileBackedByteIndexedStorage<Integer, ConcurrentHashMap<String, VariableVariantMasks>> contigStore = variantStore.getVariantMaskStorage().get(contig);
 			if(contigStore != null && contigStore.keys() != null) {
 				bucketList.addAll(contigStore.keys().stream().map(
 						(Integer bucket)->{
@@ -74,36 +74,37 @@ public BucketIndexBySample(VariantStore variantStore, String storageDir) throws
 			patientBucketCharMasks[x] = emptyBucketMaskChar();
 		}
 		contigSet.parallelStream().forEach((contig)->{
-			FileBackedByteIndexedStorage<Integer, ConcurrentHashMap<String, VariantMasks>> contigStore =
+			FileBackedByteIndexedStorage<Integer, ConcurrentHashMap<String, VariableVariantMasks>> contigStore =
 					variantStore.getVariantMaskStorage().get(contig);
 			if(contigStore != null && contigStore.keys() != null) {
 				contigStore.keys().stream().forEach(
 						(Integer bucket)->{
 							String bucketKey = contig  +  ":" + bucket;
 
 							// Create a bitmask with 1 values for each patient who has any variant in this bucket
-							BigInteger[] patientMaskForBucket = {variantStore.emptyBitmask()};
-							contigStore.get(bucket).values().forEach((VariantMasks masks)->{
+							VariantMask[] patientMaskForBucket = {new VariantMaskSparseImpl(Set.of())};
+							contigStore.get(bucket).values().forEach((VariableVariantMasks masks)->{
 								if(masks.heterozygousMask!=null) {
-									patientMaskForBucket[0] = patientMaskForBucket[0].or(masks.heterozygousMask);
+									patientMaskForBucket[0] = patientMaskForBucket[0].union(masks.heterozygousMask);
 								}
 								//add hetreo no call bits to mask
 								if(masks.heterozygousNoCallMask!=null) {
-									patientMaskForBucket[0] = patientMaskForBucket[0].or(masks.heterozygousNoCallMask);
+									patientMaskForBucket[0] = patientMaskForBucket[0].union(masks.heterozygousNoCallMask);
 								}
 								if(masks.homozygousMask!=null) {
-									patientMaskForBucket[0] = patientMaskForBucket[0].or(masks.homozygousMask);
+									patientMaskForBucket[0] = patientMaskForBucket[0].union(masks.homozygousMask);
 								}
 							});
 
 							// For each patient set the patientBucketCharMask entry to 0 or 1 if they have a variant in the bucket.
-							int maxIndex = patientMaskForBucket[0].bitLength() - 1;
+
+							// todo: implement for variant explorer
 							int indexOfBucket = Collections.binarySearch(bucketList, bucketKey) + 2; //patientBucketCharMasks has bookend bits
-							for(int x = 2;x<patientMaskForBucket[0].bitLength()-2;x++) {
-								if(patientMaskForBucket[0].testBit(maxIndex - x)) {  //testBit uses inverted indexes
-									patientBucketCharMasks[x-2][indexOfBucket] = '1';									
+							for(int x = 0; x < patientIds.size(); x++) {
+								if(patientMaskForBucket[0].testBit(x)) {
+									patientBucketCharMasks[x][indexOfBucket] = '1';
 								}else {
-									patientBucketCharMasks[x-2][indexOfBucket] = '0';
+									patientBucketCharMasks[x][indexOfBucket] = '0';
 								}
 							}
 						});

data/src/main/java/edu/harvard/hms/dbmi/avillach/hpds/data/genotype/VariableVariantMasks.java

@@ -0,0 +1,269 @@
+package edu.harvard.hms.dbmi.avillach.hpds.data.genotype;
+
+import com.fasterxml.jackson.annotation.JsonInclude;
+import com.fasterxml.jackson.annotation.JsonProperty;
+import org.slf4j.Logger;
+import org.slf4j.LoggerFactory;
+
+import java.io.Serializable;
+import java.math.BigInteger;
+import java.util.*;
+import java.util.concurrent.ConcurrentHashMap;
+import java.util.stream.Collectors;
+
+public class VariableVariantMasks implements Serializable {
+
+	private static Logger log = LoggerFactory.getLogger(VariableVariantMasks.class);
+
+	private static final long serialVersionUID = 6225420483804601477L;
+	private static final String oneone = "11";
+	private static final char one = '1';
+	private static final char zero = '0';
+	private static final String hetero = "0/1";
+	private static final String heteroDel = "1/0";
+	private static final String heteroPhased = "0|1";
+	private static final String heteroPhased2 = "1|0";
+	private static final String homo = "1/1";
+	private static final String homoPhased = "1|1";
+	private static final String homoNoCall = "./.";
+	private static final String heteroNoCall = "./1";
+
+	private static Map<Integer, BigInteger> emptyBitmaskMap = new ConcurrentHashMap<>();
+
+	public static int SPARSE_VARIANT_THRESHOLD = 5;
+
+	/*
+	 * These indices result from the char values of the 3 characters in a VCF sample
+	 * record summed as integers % 7
+	 *
+	 * This allows us to not actually do string comparisons, instead we add 3 values,
+	 * do one modulus operation, then use the result as the index into the result array.
+	 */
+
+	// ./0 = (46 + 47 + 48) % 7 = 1
+	// 0|. = (48 + 124 + 46) % 7 = 1
+	// .|0 = (46 + 124 + 48) % 7 = 1
+	public static final int HETERO_NOCALL_REF_CHAR_INDEX = 1;
+
+	// ./1 = (46 + 47 + 49) % 7 = 2
+	// 1|. = (49 + 124 + 46) % 7 = 2
+	// .|1 = (46 + 124 + 49) % 7 = 2
+	// ./1 = (46 + 47 + 49) % 7 = 2
+	// 1|. = (49 + 124 + 46) % 7 = 2
+	// .|1 = (46 + 124 + 49) % 7 = 2
+	public static final int HETERO_NOCALL_VARIANT_CHAR_INDEX = 2;
+
+	// 0/0 = (48 + 47 + 48) % 7 = 3
+	// 0|0 = (48 + 124 + 48) % 7 = 3
+	public static final int ZERO_ZERO_CHAR_INDEX = 3;
+
+	// 0/1 = (48 + 47 + 49) % 7 = 4
+	// 1|0 = (49 + 124 + 48) % 7 = 4
+	// 0|1 = (48 + 124 + 49) % 7 = 4
+	public static final int ZERO_ONE_CHAR_INDEX = 4;
+
+	// 1/1 = (49 + 47 + 49) % 7 = 5
+	// 1|1 = (49 + 124 + 49) % 7 = 5
+	public static final int ONE_ONE_CHAR_INDEX = 5;
+
+	// ./. = (46 + 47 + 46) % 7 = 6
+	// .|. = (46 + 124 + 46) % 7 = 6
+	public static final int HOMO_NOCALL_CHAR_INDEX = 6;
+
+	public VariableVariantMasks(char[][] maskValues) {
+		String heteroMaskStringRaw = new String(maskValues[ZERO_ONE_CHAR_INDEX]);
+		String homoMaskStringRaw = new String(maskValues[ONE_ONE_CHAR_INDEX]);
+		String heteroNoCallMaskStringRaw = new String(maskValues[HETERO_NOCALL_VARIANT_CHAR_INDEX]);
+		String homoNoCallMaskStringRaw = new String(maskValues[HOMO_NOCALL_CHAR_INDEX]);
+
+		heterozygousMask = variantMaskFromRawString(heteroMaskStringRaw);
+		homozygousMask = variantMaskFromRawString(homoMaskStringRaw);
+		heterozygousNoCallMask = variantMaskFromRawString(heteroNoCallMaskStringRaw);
+		homozygousNoCallMask = variantMaskFromRawString(homoNoCallMaskStringRaw);
+	}
+
+	private VariantMask variantMaskFromRawString(String maskStringRaw) {
+		if (!maskStringRaw.contains("1")) {
+			return null;
+		}
+
+		VariantMask variantMask;
+		BigInteger bitmask = new BigInteger(oneone + new StringBuilder(maskStringRaw).reverse() + oneone, 2);
+		if (bitmask.bitCount() - 4 > VariableVariantMasks.SPARSE_VARIANT_THRESHOLD) {
+			variantMask = new VariantMaskBitmaskImpl(bitmask);
+		} else {
+			Set<Integer> patientIndexes = new HashSet<>();
+			for(int i = 0; i < bitmask.bitLength() - 4; i++) {
+				// i + 2 because the mask is padded with 2 bits on each end
+				if (bitmask.testBit(i + 2)) {
+					patientIndexes.add(i);
+				}
+			}
+			variantMask = new VariantMaskSparseImpl(patientIndexes);
+		}
+		return variantMask;
+	}
+
+	public VariableVariantMasks() {
+	}
+
+	@JsonProperty("ho")
+	@JsonInclude(JsonInclude.Include.NON_NULL)
+	public VariantMask homozygousMask;
+
+	@JsonProperty("he")
+	@JsonInclude(JsonInclude.Include.NON_NULL)
+	public VariantMask heterozygousMask;
+
+	@JsonProperty("hon")
+	@JsonInclude(JsonInclude.Include.NON_NULL)
+	public VariantMask homozygousNoCallMask;
+
+	@JsonProperty("hen")
+	@JsonInclude(JsonInclude.Include.NON_NULL)
+	public VariantMask heterozygousNoCallMask;
+
+	@Override
+	public boolean equals(Object o) {
+		if (this == o) return true;
+		if (o == null || getClass() != o.getClass()) return false;
+		VariableVariantMasks that = (VariableVariantMasks) o;
+		return Objects.equals(homozygousMask, that.homozygousMask) && Objects.equals(heterozygousMask, that.heterozygousMask) && Objects.equals(homozygousNoCallMask, that.homozygousNoCallMask) && Objects.equals(heterozygousNoCallMask, that.heterozygousNoCallMask);
+	}
+
+	@Override
+	public int hashCode() {
+		return Objects.hash(homozygousMask, heterozygousMask, homozygousNoCallMask, heterozygousNoCallMask);
+	}
+
+	public static BigInteger emptyBitmask(int length) {
+		BigInteger emptyBitmask = emptyBitmaskMap.get(length);
+		if (emptyBitmask == null) {
+			String emptyVariantMask = "";
+			for (int i = 0; i < length; i++) {
+				emptyVariantMask = emptyVariantMask + "0";
+			}
+			BigInteger newEmptyBitmask = new BigInteger("11" + emptyVariantMask + "11", 2);
+			emptyBitmaskMap.put(length, newEmptyBitmask);
+			return newEmptyBitmask;
+		}
+		return emptyBitmask;
+	}
+
+	public static VariableVariantMasks append(VariableVariantMasks masks1, int length1, VariableVariantMasks masks2, int length2) {
+		VariableVariantMasks appendedMasks = new VariableVariantMasks();
+		appendedMasks.homozygousMask = appendMask(masks1.homozygousMask, masks2.homozygousMask, length1, length2);
+		appendedMasks.heterozygousMask = appendMask(masks1.heterozygousMask, masks2.heterozygousMask, length1, length2);
+		appendedMasks.homozygousNoCallMask = appendMask(masks1.homozygousNoCallMask, masks2.homozygousNoCallMask, length1, length2);
+		appendedMasks.heterozygousNoCallMask = appendMask(masks1.heterozygousNoCallMask, masks2.heterozygousNoCallMask, length1, length2);
+		return appendedMasks;
+	}
+
+	public static VariantMask appendMask(VariantMask variantMask1, VariantMask variantMask2, int length1, int length2) {
+		if (variantMask1 == null) {
+			variantMask1 = VariantMask.emptyInstance();
+		}
+		if (variantMask2 == null) {
+			variantMask2 = VariantMask.emptyInstance();
+		}
+		if (variantMask1.equals(VariantMask.emptyInstance()) && variantMask2.equals(VariantMask.emptyInstance())) {
+			return null;
+		}
+
+		if (variantMask1 instanceof  VariantMaskSparseImpl) {
+			if (variantMask2 instanceof VariantMaskSparseImpl) {
+				return append((VariantMaskSparseImpl) variantMask1, (VariantMaskSparseImpl) variantMask2, length1, length2);
+			} else if (variantMask2 instanceof  VariantMaskBitmaskImpl) {
+				return append((VariantMaskSparseImpl) variantMask1, (VariantMaskBitmaskImpl) variantMask2, length1, length2);
+			} else {
+				throw new RuntimeException("Unknown VariantMask implementation");
+			}
+		}
+		else if (variantMask1 instanceof  VariantMaskBitmaskImpl) {
+			if (variantMask2 instanceof VariantMaskSparseImpl) {
+				return append((VariantMaskBitmaskImpl) variantMask1, (VariantMaskSparseImpl) variantMask2, length1, length2);
+			} else if (variantMask2 instanceof  VariantMaskBitmaskImpl) {
+				return append((VariantMaskBitmaskImpl) variantMask1, (VariantMaskBitmaskImpl) variantMask2, length1, length2);
+			} else {
+				throw new RuntimeException("Unknown VariantMask implementation");
+			}
+		}
+		else {
+			throw new RuntimeException("Unknown VariantMask implementation");
+		}
+	}
+
+	private static VariantMask append(VariantMaskSparseImpl variantMask1, VariantMaskBitmaskImpl variantMask2, int length1, int length2) {
+		BigInteger mask1 = emptyBitmask(length1);
+		for (Integer patientIndex : variantMask1.patientIndexes) {
+			mask1 = mask1.setBit(patientIndex + 2);
+		}
+		String binaryMask1 = mask1.toString(2);
+
+		String binaryMask2 = variantMask2.bitmask.toString(2);
+		if (binaryMask2.length() - 4 != length2) {
+			throw new IllegalArgumentException("Bitmask does not match length (" + length2 + "): " + variantMask2.bitmask);
+		}
+
+		String appendedString = binaryMask2.substring(0, binaryMask2.length() - 2) +
+				binaryMask1.substring(2);
+		return new VariantMaskBitmaskImpl(new BigInteger(appendedString, 2));
+	}
+
+	private static VariantMask append(VariantMaskBitmaskImpl variantMask1, VariantMaskSparseImpl variantMask2, int length1, int length2) {
+		String binaryMask1 = variantMask1.bitmask.toString(2);
+		if (binaryMask1.length() - 4 != length1) {
+			throw new IllegalArgumentException("Bitmask does not match length (" + length1 + "): " + variantMask1.bitmask);
+		}
+
+		BigInteger mask2 = emptyBitmask(length2);
+		for (Integer patientId : variantMask2.patientIndexes) {
+			mask2 = mask2.setBit(patientId + 2);
+		}
+		String binaryMask2 = mask2.toString(2);
+
+		String appendedString = binaryMask2.substring(0, binaryMask2.length() - 2) +
+				binaryMask1.substring(2);
+		return new VariantMaskBitmaskImpl(new BigInteger(appendedString, 2));
+	}
+
+	private static VariantMask append(VariantMaskBitmaskImpl variantMask1, VariantMaskBitmaskImpl variantMask2, int length1, int length2) {
+		String binaryMask1 = variantMask1.bitmask.toString(2);
+		String binaryMask2 = variantMask2.bitmask.toString(2);
+
+		if (binaryMask1.length() - 4 != length1) {
+			throw new IllegalArgumentException("Bitmask does not match length (" + length1 + "): " + variantMask1.bitmask);
+		}
+		if (binaryMask2.length() - 4 != length2) {
+			throw new IllegalArgumentException("Bitmask does not match length (" + length2 + "): " + variantMask2.bitmask);
+		}
+
+		String appendedString = binaryMask2.substring(0, binaryMask2.length() - 2) +
+				binaryMask1.substring(2);
+		BigInteger bitmask = new BigInteger(appendedString, 2);
+		return new VariantMaskBitmaskImpl(bitmask);
+	}
+
+	private static VariantMask append(VariantMaskSparseImpl variantMask1, VariantMaskSparseImpl variantMask2, int length1, int length2) {
+		if (variantMask1.patientIndexes.size() + variantMask2.patientIndexes.size() > SPARSE_VARIANT_THRESHOLD) {
+			BigInteger mask = emptyBitmask(length1 + length2);
+			for (Integer patientId : variantMask1.patientIndexes) {
+				mask = mask.setBit(patientId + 2);
+			}
+			// We start writing mask 2 where mask 1 ends. So the 0th index of mask 2 is now following the last bit of mask 1
+			for (Integer patientId : variantMask2.patientIndexes) {
+				mask = mask.setBit(patientId + length1 + 2);
+			}
+			return new VariantMaskBitmaskImpl(mask);
+		}
+		else {
+			Set<Integer> patientIndexSet = new HashSet<>();
+			patientIndexSet.addAll(variantMask1.patientIndexes);
+			// The indexes for mask 2 are shifted by the length of mask 1, corresponding to the corresponding patient id array
+			// for mask 2 being appended to those of mask 1
+			patientIndexSet.addAll(variantMask2.patientIndexes.stream().map(i -> i + length1).collect(Collectors.toSet()));
+			return new VariantMaskSparseImpl(patientIndexSet);
+		}
+	}
+
+}

data/src/main/java/edu/harvard/hms/dbmi/avillach/hpds/data/genotype/VariantMask.java

@@ -0,0 +1,36 @@
+package edu.harvard.hms.dbmi.avillach.hpds.data.genotype;
+
+import com.fasterxml.jackson.annotation.JsonSubTypes;
+import com.fasterxml.jackson.annotation.JsonTypeInfo;
+
+import java.math.BigInteger;
+import java.util.List;
+import java.util.Set;
+import java.util.stream.Collectors;
+
+@JsonTypeInfo(
+        use = JsonTypeInfo.Id.NAME,
+        include = JsonTypeInfo.As.PROPERTY,
+        property = "type",
+        defaultImpl = VariantMaskBitmaskImpl.class
+)
+@JsonSubTypes({
+        @JsonSubTypes.Type(value = VariantMaskBitmaskImpl.class, name = "b"),
+        @JsonSubTypes.Type(value = VariantMaskSparseImpl.class, name = "s")
+})
+public interface VariantMask {
+
+    VariantMask intersection(VariantMask variantMask);
+
+    VariantMask union(VariantMask variantMask);
+
+    boolean testBit(int bit);
+
+    int bitCount();
+
+    static VariantMask emptyInstance() {
+        return new VariantMaskSparseImpl(Set.of());
+    }
+
+    Set<Integer> patientMaskToPatientIdSet(List<String> patientIds);
+}