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variantkey.h
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variantkey.h
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// VariantKey
//
// variantkey.h
//
// @category Libraries
// @author Nicola Asuni <[email protected]>
// @link https://github.com/tecnickcom/variantkey
// @license MIT [LICENSE](https://raw.githubusercontent.com/tecnickcom/variantkey/main/LICENSE)
// @copyright 2017-2018 GENOMICS plc, 2018-2023 Nicola Asuni - Tecnick.com
//
// LICENSE
//
// Copyright (c) 2017-2018 GENOMICS plc
// Copyright (c) 2018-2023 Nicola Asuni - Tecnick.com
//
// Permission is hereby granted, free of charge, to any person obtaining a copy
// of this software and associated documentation files (the "Software"), to deal
// in the Software without restriction, including without limitation the rights
// to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
// copies of the Software, and to permit persons to whom the Software is
// furnished to do so, subject to the following conditions:
//
// The above copyright notice and this permission notice shall be included in
// all copies or substantial portions of the Software.
//
// THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
// IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
// FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
// AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
// LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
// OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN
// THE SOFTWARE.
/**
* @file variantkey.h
* @brief VariantKey main functions.
*
* The functions provided here allow the generation and processing of a 64 bit Unsigned Integer Keys for Human Genetic Variants.
* The VariantKey is sortable for chromosome and position,
* and it is also fully reversible for variants with up to 11 bases between Reference and Alternate alleles.
* It can be used to sort, search and match variant-based data easily and very quickly.
*/
#ifndef VARIANTKEY_H
#define VARIANTKEY_H
#include <inttypes.h>
#include <stddef.h>
#include <stdio.h>
#include "hex.h"
#define VKMASK_CHROM 0xF800000000000000 //!< VariantKey binary mask for CHROM [ 11111000 00000000 00000000 00000000 00000000 00000000 00000000 00000000 ]
#define VKMASK_POS 0x07FFFFFF80000000 //!< VariantKey binary mask for POS [ 00000111 11111111 11111111 11111111 10000000 00000000 00000000 00000000 ]
#define VKMASK_CHROMPOS 0xFFFFFFFF80000000 //!< VariantKey binary mask for CHROM+POS [ 11111111 11111111 11111111 11111111 10000000 00000000 00000000 00000000 ]
#define VKMASK_REFALT 0x000000007FFFFFFF //!< VariantKey binary mask for REF+ALT [ 00000000 00000000 00000000 00000000 01111111 11111111 11111111 11111111 ]
#define VKSHIFT_CHROM 59 //!< CHROM LSB position from the VariantKey LSB
#define VKSHIFT_POS 31 //!< POS LSB position from the VariantKey LSB
#define MAXUINT32 0xFFFFFFFF //!< Maximum value for uint32_t
/**
* VariantKey struct.
* Contains the numerically encoded VariantKey components (CHROM, POS, REF+ALT).
*/
typedef struct variantkey_t
{
uint8_t chrom; //!< Chromosome encoded number (only the LSB 5 bit are used)
uint32_t pos; //!< Reference position, with the first base having position 0 (only the LSB 28 bit are used)
uint32_t refalt; //!< Code for Reference and Alternate allele (only the LSB 31 bits are used)
} variantkey_t;
/**
* Struct containing the minimum and maximum VariantKey values for range searches.
*/
typedef struct vkrange_t
{
uint64_t min; //!< Minimum VariantKey value for any given REF+ALT encoding
uint64_t max; //!< Maximum VariantKey value for any given REF+ALT encoding
} vkrange_t;
/** @brief Returns the encoding for a numerical chromosome input.
*
* @param chrom Chromosome. An identifier from the reference genome, no white-space permitted.
* @param size Length of the chrom string, excluding the terminating null byte.
*
* @return CHROM code
*/
static inline uint8_t encode_numeric_chrom(const char *chrom, size_t size)
{
size_t i;
uint8_t v = (chrom[0] - '0');
for (i = 1; i < size; i++)
{
if ((chrom[i] > '9') || (chrom[i] < '0'))
{
return 0; // NA: a character that is not a number was found.
}
v = ((v * 10) + (chrom[i] - '0'));
}
return v;
}
/** @brief Returns a true value (1) if the input chrom has 'chr' prefix (case insensitive).
*
* @param chrom Chromosome. An identifier from the reference genome, no white-space permitted.
* @param size Length of the chrom string, excluding the terminating null byte.
*
* @return True (1) if the chr prefix is present.
*/
static inline int has_chrom_chr_prefix(const char *chrom, size_t size)
{
return ((size > 3)
&& ((chrom[0] == 'c') || (chrom[0] == 'C'))
&& ((chrom[1] == 'h') || (chrom[1] == 'H'))
&& ((chrom[2] == 'r') || (chrom[2] == 'R')));
}
/** @brief Returns chromosome numerical encoding.
*
* @param chrom Chromosome. An identifier from the reference genome, no white-space permitted.
* @param size Length of the chrom string, excluding the terminating null byte.
*
* @return CHROM code or 0 in case of invalid input.
*/
static inline uint8_t encode_chrom(const char *chrom, size_t size)
{
// X = 23; Y = 24; M = 25; any other letter is mapped to 0:
static const uint8_t onecharmap[] =
{
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, 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, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/* M X Y */
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,25, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,23,24, 0, 0, 0, 0, 0, 0,
/* m x y */
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,25, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,23,24, 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, 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, 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, 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, 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, 0, 0, 0, 0, 0, 0, 0, 0, 0,
};
if (has_chrom_chr_prefix(chrom, size))
{
// remove "chr" prefix
chrom += 3;
size -= 3;
}
if (size == 0)
{
return 0;
}
if ((chrom[0] <= '9') && (chrom[0] >= '0'))
{
return encode_numeric_chrom(chrom, size);
}
if ((size == 1) || ((size == 2) && ((chrom[1] == 'T') || (chrom[1] == 't'))))
{
return onecharmap[((uint8_t)chrom[0])];
}
return 0; // NA
}
/** @brief Decode the chromosome numerical code.
*
* @param code CHROM code.
* @param chrom CHROM string buffer to be returned. Its size should be enough to contain the results (max 4 bytes).
*
* @return If successful, the total number of characters written is returned,
* excluding the null-character appended at the end of the string,
* otherwise a negative number is returned in case of failure.
*/
static inline size_t decode_chrom(uint8_t code, char *chrom)
{
if ((code < 1) || (code > 25))
{
return sprintf(chrom, "NA");
}
if (code < 23)
{
return sprintf(chrom, "%" PRIu8, code);
}
static const char *map[] = {"X", "Y", "MT"};
return sprintf(chrom, "%s", map[(code - 23)]);
}
static inline uint32_t encode_base(const uint8_t c)
{
/*
Encode base:
A = 0
C = 1
G = 2
T = 3
*/
static const uint32_t map[] =
{
4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,
4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,
/*A C G T*/
4,0,4,1,4,4,4,2,4,4,4,4,4,4,4,4,4,4,4,4,3,4,4,4,4,4,4,4,4,4,4,4,
/*a c g t*/
4,0,4,1,4,4,4,2,4,4,4,4,4,4,4,4,4,4,4,4,3,4,4,4,4,4,4,4,4,4,4,4,
4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,
4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,
4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,
4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,4,
};
return map[c];
}
static inline int encode_allele(uint32_t *h, uint8_t *bitpos, const char *str, size_t size)
{
uint32_t v;
while (size--)
{
v = encode_base(*str++);
if (v > 3)
{
return -1;
}
*bitpos -= 2;
*h |= (v << *bitpos);
}
return 0;
}
static inline uint32_t encode_refalt_rev(const char *ref, size_t sizeref, const char *alt, size_t sizealt)
{
//[******** ******** ******** ******** *RRRRAAA A1122334 45566778 8990011*]
uint32_t h = 0;
h |= ((uint32_t)(sizeref) << 27); // RRRR: length of (REF - 1)
h |= ((uint32_t)(sizealt) << 23); // AAAA: length of (ALT - 1)
uint8_t bitpos = 23;
if ((encode_allele(&h, &bitpos, ref, sizeref) < 0) || (encode_allele(&h, &bitpos, alt, sizealt) < 0))
{
return MAXUINT32; // error code
}
return h;
}
// Mix two 32 bit hash numbers using a MurmurHash3-like algorithm
static inline uint32_t muxhash(uint32_t k, uint32_t h)
{
k *= 0xcc9e2d51;
k = (k >> 17) | (k << 15);
k *= 0x1b873593;
h ^= k;
h = (h >> 19) | (h << 13);
return ((h * 5) + 0xe6546b64);
}
static inline uint32_t encode_packchar(int c)
{
if (c < 'A')
{
return 27;
}
if (c >= 'a')
{
return (uint32_t)(c - 'a' + 1);
}
return (uint32_t)(c - 'A' + 1);
}
// pack blocks of 6 characters in 32 bit (6 x 5 bit + 2 spare bit) [ 01111122 22233333 44444555 55666660 ]
static inline uint32_t pack_chars_tail(const char *str, size_t size)
{
uint32_t h = 0;
const char *pos = (str + size - 1);
switch (size)
{
case 5:
h ^= encode_packchar(*pos--) << (1 + (5 * 1));
// fall through
case 4:
h ^= encode_packchar(*pos--) << (1 + (5 * 2));
// fall through
case 3:
h ^= encode_packchar(*pos--) << (1 + (5 * 3));
// fall through
case 2:
h ^= encode_packchar(*pos--) << (1 + (5 * 4));
// fall through
case 1:
h ^= encode_packchar(*pos) << (1 + (5 * 5));
}
return h;
}
static inline uint32_t pack_chars(const char *str)
{
const char *pos = (str + 5);
return ((encode_packchar(*pos) << 1)
^ (encode_packchar(*(pos-1)) << (1 + (5 * 1)))
^ (encode_packchar(*(pos-2)) << (1 + (5 * 2)))
^ (encode_packchar(*(pos-3)) << (1 + (5 * 3)))
^ (encode_packchar(*(pos-4)) << (1 + (5 * 4)))
^ (encode_packchar(*(pos-5)) << (1 + (5 * 5))));
}
// Return a 32 bit hash of a nucleotide string
static inline uint32_t hash32(const char *str, size_t size)
{
uint32_t h = 0;
size_t len = 6;
while (size >= len)
{
h = muxhash(pack_chars(str), h);
str += len;
size -= len;
}
if (size > 0)
{
h = muxhash(pack_chars_tail(str, size), h);
}
return h;
}
static inline uint32_t encode_refalt_hash(const char *ref, size_t sizeref, const char *alt, size_t sizealt)
{
// 0x3 is the separator character between REF and ALT [00000000 00000000 00000000 00000011]
uint32_t h = muxhash(hash32(alt, sizealt), muxhash(0x3, hash32(ref, sizeref)));
// MurmurHash3 finalization mix - force all bits of a hash block to avalanche
h ^= h >> 16;
h *= 0x85ebca6b;
h ^= h >> 13;
h *= 0xc2b2ae35;
h ^= h >> 16;
return ((h >> 1) | 0x1); // 0x1 is the set bit to indicate HASH mode [00000000 00000000 00000000 00000001]
}
/** @brief Returns reference+alternate numerical encoding.
*
* @param ref Reference allele. String containing a sequence of nucleotide letters.
* The value in the pos field refers to the position of the first nucleotide in the String.
* Characters must be A-Z, a-z or *
* @param sizeref Length of the ref string, excluding the terminating null byte.
* @param alt Alternate non-reference allele string.
* Characters must be A-Z, a-z or *
* @param sizealt Length of the alt string, excluding the terminating null byte.
*
* @return REF+ALT code
*/
static inline uint32_t encode_refalt(const char *ref, size_t sizeref, const char *alt, size_t sizealt)
{
if ((sizeref + sizealt) <= 11)
{
uint32_t h = encode_refalt_rev(ref, sizeref, alt, sizealt);
if (h != MAXUINT32)
{
return h;
}
}
return encode_refalt_hash(ref, sizeref, alt, sizealt);
}
static inline char decode_base(uint32_t code, int bitpos)
{
static const char base[4] = {'A', 'C', 'G', 'T'};
return base[((code >> bitpos) & 0x3)]; // 0x3 is the 2 bit mask [00000011]
}
static inline size_t decode_refalt_rev(uint32_t code, char *ref, size_t *sizeref, char *alt, size_t *sizealt)
{
*sizeref = (size_t)((code & 0x78000000) >> 27); // [01111000 00000000 00000000 00000000]
*sizealt = (size_t)((code & 0x07800000) >> 23); // [00000111 10000000 00000000 00000000]
switch (*sizeref)
{
case 10:
ref[9] = decode_base(code, (3 + (2 * 0)));
// fall through
case 9:
ref[8] = decode_base(code, (3 + (2 * 1)));
// fall through
case 8:
ref[7] = decode_base(code, (3 + (2 * 2)));
// fall through
case 7:
ref[6] = decode_base(code, (3 + (2 * 3)));
// fall through
case 6:
ref[5] = decode_base(code, (3 + (2 * 4)));
// fall through
case 5:
ref[4] = decode_base(code, (3 + (2 * 5)));
// fall through
case 4:
ref[3] = decode_base(code, (3 + (2 * 6)));
// fall through
case 3:
ref[2] = decode_base(code, (3 + (2 * 7)));
// fall through
case 2:
ref[1] = decode_base(code, (3 + (2 * 8)));
// fall through
case 1:
ref[0] = decode_base(code, (3 + (2 * 9)));
}
ref[*sizeref] = 0;
uint8_t bitpos = (23 - ((*sizeref) << 1));
switch (*sizealt)
{
case 10:
alt[9] = decode_base(code, bitpos - (2 * 10));
// fall through
case 9:
alt[8] = decode_base(code, bitpos - (2 * 9));
// fall through
case 8:
alt[7] = decode_base(code, bitpos - (2 * 8));
// fall through
case 7:
alt[6] = decode_base(code, bitpos - (2 * 7));
// fall through
case 6:
alt[5] = decode_base(code, bitpos - (2 * 6));
// fall through
case 5:
alt[4] = decode_base(code, bitpos - (2 * 5));
// fall through
case 4:
alt[3] = decode_base(code, bitpos - (2 * 4));
// fall through
case 3:
alt[2] = decode_base(code, bitpos - (2 * 3));
// fall through
case 2:
alt[1] = decode_base(code, bitpos - (2 * 2));
// fall through
case 1:
alt[0] = decode_base(code, bitpos - (2 * 1));
}
alt[*sizealt] = 0;
return (*sizeref + *sizealt);
}
/** @brief Decode the 32 bit REF+ALT code if reversible (if it has 11 or less bases in total and only contains ACGT letters).
*
* @param code REF+ALT code
* @param ref REF string buffer to be returned.
* @param sizeref Pointer to the size of the ref buffer, excluding the terminating null byte.
* This will contain the final ref size.
* @param alt ALT string buffer to be returned.
* @param sizealt Pointer to the size of the alt buffer, excluding the terminating null byte.
* This will contain the final alt size.
*
* @return If the code is reversible, then the total number of characters of REF+ALT is returned.
* Otherwise 0 is returned.
*/
static inline size_t decode_refalt(uint32_t code, char *ref, size_t *sizeref, char *alt, size_t *sizealt)
{
if (code & 0x1) // check last bit
{
return 0; // non-reversible encoding
}
return decode_refalt_rev(code, ref, sizeref, alt, sizealt);
}
/** @brief Returns a 64 bit variant key based on the pre-encoded CHROM, POS (0-based) and REF+ALT.
*
* @param chrom Encoded Chromosome (see encode_chrom).
* @param pos Position. The reference position, with the first base having position 0.
* @param refalt Encoded Reference + Alternate (see encode_refalt).
*
* @return VariantKey 64 bit code.
*/
static inline uint64_t encode_variantkey(uint8_t chrom, uint32_t pos, uint32_t refalt)
{
return (((uint64_t)chrom << VKSHIFT_CHROM) | ((uint64_t)pos << VKSHIFT_POS) | (uint64_t)refalt);
}
/** @brief Extract the CHROM code from VariantKey.
*
* @param vk VariantKey code.
*
* @return CHROM code.
*/
static inline uint8_t extract_variantkey_chrom(uint64_t vk)
{
return (uint8_t)((vk & VKMASK_CHROM) >> VKSHIFT_CHROM);
}
/** @brief Extract the POS code from VariantKey.
*
* @param vk VariantKey code.
*
* @return POS.
*/
static inline uint32_t extract_variantkey_pos(uint64_t vk)
{
return (uint32_t)((vk & VKMASK_POS) >> VKSHIFT_POS);
}
/** @brief Extract the REF+ALT code from VariantKey.
*
* @param vk VariantKey code.
*
* @return REF+ALT code.
*/
static inline uint32_t extract_variantkey_refalt(uint64_t vk)
{
return (uint32_t)(vk & VKMASK_REFALT);
}
/** @brief Decode a VariantKey code and returns the components as variantkey_t structure.
*
* @param code VariantKey code.
* @param vk Decoded variantkey structure.
*/
static inline void decode_variantkey(uint64_t code, variantkey_t *vk)
{
vk->chrom = extract_variantkey_chrom(code);
vk->pos = extract_variantkey_pos(code);
vk->refalt = extract_variantkey_refalt(code);
}
/**
* Returns a 64 bit variant key based on CHROM, POS (0-based), REF, ALT.
* The variant should be already normalized (see normalize_variant or use normalized_variantkey).
*
* @param chrom Chromosome. An identifier from the reference genome, no white-space or leading zeros permitted.
* @param sizechrom Length of the chrom string, excluding the terminating null byte.
* @param pos Position. The reference position, with the first base having position 0.
* @param ref Reference allele. String containing a sequence of nucleotide letters.
* The value in the pos field refers to the position of the first nucleotide in the String.
* Characters must be A-Z, a-z or *
* @param sizeref Length of the ref string, excluding the terminating null byte.
* @param alt Alternate non-reference allele string.
* Characters must be A-Z, a-z or *
* @param sizealt Length of the alt string, excluding the terminating null byte.
*
* @return VariantKey 64 bit code.
*/
static inline uint64_t variantkey(const char *chrom, size_t sizechrom, uint32_t pos, const char *ref, size_t sizeref, const char *alt, size_t sizealt)
{
return encode_variantkey(encode_chrom(chrom, sizechrom), pos, encode_refalt(ref, sizeref, alt, sizealt));
}
/** @brief Returns minimum and maximum VariantKeys for range searches.
*
* @param chrom Chromosome encoded number.
* @param pos_min Start reference position, with the first base having position 0.
* @param pos_max End reference position, with the first base having position 0.
* @param range VariantKey range values.
*/
static inline void variantkey_range(uint8_t chrom, uint32_t pos_min, uint32_t pos_max, vkrange_t *range)
{
uint64_t c = ((uint64_t)chrom << VKSHIFT_CHROM);
range->min = (c | ((uint64_t)pos_min << VKSHIFT_POS));
range->max = (c | ((uint64_t)pos_max << VKSHIFT_POS) | VKMASK_REFALT);
}
static inline int8_t compare_uint64_t(uint64_t a, uint64_t b)
{
return (a < b) ? -1 : (a > b);
}
/** @brief Compares two VariantKeys by chromosome only.
*
* @param vka The first VariantKey to be compared.
* @param vkb The second VariantKey to be compared.
*
* @return -1 if the first chromosome is smaller than the second, 0 if they are equal and 1 if the first is greater than the second.
*/
static inline int8_t compare_variantkey_chrom(uint64_t vka, uint64_t vkb)
{
return compare_uint64_t((vka >> VKSHIFT_CHROM), (vkb >> VKSHIFT_CHROM));
}
/** @brief Compares two VariantKeys by chromosome and position.
*
* @param vka The first VariantKey to be compared.
* @param vkb The second VariantKey to be compared.
*
* @return -1 if the first CHROM+POS is smaller than the second, 0 if they are equal and 1 if the first is greater than the second.
*/
static inline int8_t compare_variantkey_chrom_pos(uint64_t vka, uint64_t vkb)
{
return compare_uint64_t((vka >> VKSHIFT_POS), (vkb >> VKSHIFT_POS));
}
/** @brief Returns VariantKey hexadecimal string (16 characters).
*
* The string represent a 64 bit number or:
* - 5 bit for CHROM
* - 28 bit for POS
* - 31 bit for REF+ALT
*
* @param vk VariantKey code.
* @param str String buffer to be returned (it must be sized 17 bytes at least).
*
* @return Upon successful return, these function returns the number of characters processed
* (excluding the null byte used to end output to strings).
* If the buffer size is not sufficient, then the return value is the number of characters required for
* buffer string, including the terminating null byte.
*/
static inline size_t variantkey_hex(uint64_t vk, char *str)
{
return hex_uint64_t(vk, str);
}
/** @brief Parses a VariantKey hexadecimal string and returns the code.
*
* @param vs VariantKey hexadecimal string (it must contain 16 hexadecimal characters).
*
* @return A VariantKey code.
*/
static inline uint64_t parse_variantkey_hex(const char *vs)
{
return parse_hex_uint64_t(vs);
}
#endif // VARIANTKEY_H