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/**
* @file dozeu_interface.hpp
* @author Hajime Suzuki
* @date 2018/03/23
*/
#ifndef VG_DOZEU_INTERFACE_HPP_INCLUDED
#define VG_DOZEU_INTERFACE_HPP_INCLUDED
#include <algorithm>
#include <cstdint>
#include <functional>
#include <unordered_map>
#include <vector>
#include <vg/vg.pb.h>
#include "types.hpp"
#include "handle.hpp"
#include "mem.hpp"
// #define BENCH
// #include "bench.h"
// forward declarations of dozeu structs
struct dz_s;
struct dz_forefront_s;
struct dz_query_s;
struct dz_alignment_s;
namespace vg {
static constexpr uint16_t default_xdrop_max_gap_length = 40;
/**
* Align to a graph using the xdrop algorithm, as implemented in dozeu.
*
* The underlying Dozeu library is fundamentally based around semi-global
* alignment: extending an alignment from a known matching position (what
* in other parts of vg we call "pinned" alignment).
*
* To simulate non-pinned alignment, we align in two passes in different
* directions. One from a guess of a pinning position, to get a more
* accurate "head" pinning position for the other end, and once back from
* where the previous pass ended up, to get an overall hopefully-optimal
* alignment.
*
* If the input graph is not reverse-complemented, direction = false
* (reverse, right to left) on the first pass, and direction = true
* (forward, left to right) on the second. If it is reverse complemented,
* we flip them.
*
* This won't actually work in theory to get the optimal local alignment in
* all cases, but it works well in practice.
*
* This class maintains an internal dz_s, which is *NOT THREADSAFE*,
* and non-const during alignments. However, it may be reused for
* subsequent alignments.
*/
class DozeuInterface {
public:
virtual ~DozeuInterface() = default;
/**
* align query: forward-backward banded alignment
*
* Compute an alignment of the given Alignment's sequence against the
* given DAG, using (one of) the given MEMs to seed the alignment.
*
* reverse_complemented is true if the topologically sorted graph we
* have was reverse-complemented when extracted from a larger
* containing graph, and false if it is in the same orientation as it
* exists in the larger containing graph. The MEMs and the Alignment
* are interpreted as being against the forward strand of the passed
* subgraph no matter the value of this setting.
*
* reverse_complemented true means we will compute the alignment
* forward in the topologically-sorted order of the given graph
* (anchoring to the first node if no MEMs are provided) and false if
* we want to compute the alignment backward in the topological order
* (anchoring to the last node).
*
* First the head (the most upstream) seed in MEMs is selected and
* extended downward to detect the downstream breakpoint. Next the
* alignment path is generated by second upward extension from the
* downstream breakpoint.
*
* The MEM list may be empty. If MEMs are provided, uses only the
* begin, end, and nodes fields of the MaximalExactMatch objects. It
* uses the first occurrence of the last MEM if reverse_complemented is
* true, and the last occurrence of the first MEM otherwise.
*/
void align(Alignment& alignment, const HandleGraph& graph, const vector<MaximalExactMatch>& mems,
bool reverse_complemented, int8_t full_length_bonus,
uint16_t max_gap_length = default_xdrop_max_gap_length);
/**
* Same as above except using a precomputed topological order, which
* need not include all handles in the graph, and which may contain both
* orientations of a handle.
*/
void align(Alignment& alignment, const HandleGraph& graph, const vector<handle_t>& order,
const vector<MaximalExactMatch>& mems, bool reverse_complemented,
int8_t full_length_bonus, uint16_t max_gap_length = default_xdrop_max_gap_length);
/**
* Compute a pinned alignment, where the start (pin_left=true) or end
* (pin_left=false) end of the Alignment sequence is pinned to the
* start of the first (pin_left=true) or end of the last
* (pin_left=false) node in the graph's topological order.
*
* Does not account for multiple sources/sinks in the topological
* order; whichever comes first/last ends up being used for the pin.
*/
void align_pinned(Alignment& alignment, const HandleGraph& g, bool pin_left,
int8_t full_length_bonus, uint16_t max_gap_length = default_xdrop_max_gap_length);
protected:
/**
* Represents a correspondance between a position in the subgraph we are
* mapping to and a position in the read we are mapping.
*/
struct graph_pos_s {
/// What index in the node list of our extracted subgraph is our node at?
size_t node_index;
/// What is the offset in the node? Note that we only think about the forward strand.
uint32_t ref_offset;
/// What is the correspondign offset in the query sequence?
uint32_t query_offset;
};
/**
* Represents a HandleGraph with a defined (topological) order calculated for it.
*/
struct OrderedGraph {
OrderedGraph(const HandleGraph& graph, const vector<handle_t>& order);
void for_each_neighbor(const size_t i, bool go_left, const function<void(size_t)>& lambda) const;
size_t size() const;
const HandleGraph& graph;
const vector<handle_t>& order;
unordered_map<handle_t, size_t> index_of;
};
// wrappers for dozeu functions that can be used to toggle between between quality
// adjusted and standard alignments
virtual dz_query_s* pack_query_forward(const char* seq, const uint8_t* qual,
int8_t full_length_bonus, size_t len) = 0;
virtual dz_query_s* pack_query_reverse(const char* seq, const uint8_t* qual,
int8_t full_length_bonus, size_t len) = 0;
virtual const dz_forefront_s* scan(const dz_query_s* query, const dz_forefront_s** forefronts,
size_t n_forefronts, const char* ref, int32_t rlen, uint32_t rid,
uint16_t xt) = 0;
virtual const dz_forefront_s* extend(const dz_query_s* query, const dz_forefront_s** forefronts,
size_t n_forefronts, const char* ref, int32_t rlen,
uint32_t rid, uint16_t xt) = 0;
virtual dz_alignment_s* trace(const dz_forefront_s* forefront) = 0;
virtual void flush() = 0;
/// Given the subgraph we are aligning to, the MEM hist against it, the
/// length of the query, and the direction we are aligning the query in
/// (true = forward), select a single anchoring match between the graph
/// and the query to align out from.
///
/// This replaces scan_seed_position for the case where we have MEMs.
graph_pos_s calculate_seed_position(const OrderedGraph& graph, const vector<MaximalExactMatch>& mems,
size_t query_length, bool direction) const;
/// Given the index of the node at which the winning score occurs, find
/// the position in the node and read sequence at which the winning
/// match is found.
graph_pos_s calculate_max_position(const OrderedGraph& graph, const graph_pos_s& seed_pos,
size_t max_node_index, bool direction,
const vector<const dz_forefront_s*>& forefronts);
/// If no seeds are provided as alignment input, we need to compute our own starting anchor position. This function does that.
/// Takes the topologically-sorted graph, the query sequence, and the direction.
/// If direction is false, finds a seed hit on the first node of the graph. If it is true, finds a hit on the last node.
///
/// This replaces calculate_seed_position for the case where we have no MEMs.
///
/// The bool return with the position indicates whether the scan succeeded or failed.
/// If the scan failed, then the alignment should not be attempted.
pair<graph_pos_s, bool> scan_seed_position(const OrderedGraph& graph, const Alignment& alignment,
bool direction, vector<const dz_forefront_s*>& forefronts,
int8_t full_length_bonus, uint16_t max_gap_length);
/// Append an edit at the end of the current mapping array.
/// Returns the length passed in.
size_t push_edit(Mapping *mapping, uint8_t op, const char* alt, size_t len) const;
/// Do alignment. Takes the graph, the sorted packed edges in
/// ascending order for a forward pass or descending order for a
/// reverse pass, the packed query sequence, the index of the seed node
/// in the graph, the offset (TODO: in the read?) of the seed position,
/// and the direction to traverse the graph topological order.
///
/// Note that we take our direction as right_to_left, whole many other
/// functions take it as left_to_right.
///
/// If a MEM seed is provided, this is run in two passes. The first is
/// left to right (right_to_left = false) if align did not have
/// reverse_complement set and the second is right to left (right_to_left =
/// true).
///
/// If we have no MEM seed, we only run one pass (the second one).
///
/// Returns the index in the topological order of the node with the
/// highest scoring alignment.
///
/// Note that if no non-empty local alignment is found, it may not be
/// safe to call dz_calc_max_qpos on the associated forefront!
size_t do_poa(const OrderedGraph& graph, const dz_query_s* packed_query,
const vector<graph_pos_s>& seed_positions, bool right_to_left,
vector<const dz_forefront_s*>& forefronts, uint16_t);
/**
* After all the alignment work has been done, do the traceback and
* save into the given Alignment object.
*
* If left_to_right is true, the nodes were filled left to right, and
* the internal traceback will come out in left to right order, so we
* can emit it as is. If it is false, the nodes were filled right to
* left, and the internal traceback comes out in right to left order,
* so we need to flip it.
*/
void calculate_and_save_alignment(Alignment& alignment, const OrderedGraph& graph,
const vector<graph_pos_s>& head_positions,
size_t tail_node_index, bool left_to_right,
const vector<const dz_forefront_s*>& forefronts);
// void debug_print(Alignment const &alignment, OrderedGraph const &graph, MaximalExactMatch const &seed, bool reverse_complemented);
// bench_t bench;
/// After doing the upward pass and finding head_pos to anchor from, do
/// the downward alignment pass and traceback. If left_to_right is
/// set, goes left to right and traces back the other way. If it is
/// unset, goes right to left and traces back the other way.
void align_downward(Alignment &alignment, const OrderedGraph& graph,
const vector<graph_pos_s>& head_positions,
bool left_to_right, vector<const dz_forefront_s*>& forefronts,
int8_t full_length_bonus, uint16_t max_gap_length);
/// The core dozeu class, which does the alignments
dz_s* dz = nullptr;
};
/*
* A dozeu-backed X-drop aligner that does not use base qualities
* to adjust alignment scores.
*/
class XdropAligner : public DozeuInterface {
public:
/// Main constructor. Expects a 4 x 4 score matrix.
XdropAligner(const int8_t* _score_matrix,
int8_t _gap_open,
int8_t _gap_extension);
// see DozeuInterface::align and DozeuInterface::align_pinned below for alignment
// interface
private:
// implementations of virtual functions from DozeuInterface
dz_query_s* pack_query_forward(const char* seq, const uint8_t* qual, int8_t full_length_bonus, size_t len);
dz_query_s* pack_query_reverse(const char* seq, const uint8_t* qual, int8_t full_length_bonus, size_t len);
const dz_forefront_s* scan(const dz_query_s* query, const dz_forefront_s** forefronts,
size_t n_forefronts, const char* ref, int32_t rlen, uint32_t rid,
uint16_t xt);
const dz_forefront_s* extend(const dz_query_s* query, const dz_forefront_s** forefronts,
size_t n_forefronts, const char* ref, int32_t rlen,
uint32_t rid, uint16_t xt);
dz_alignment_s* trace(const dz_forefront_s* forefront);
void flush();
public:
XdropAligner() = default;
~XdropAligner(void);
/// Copy constructor
XdropAligner(const XdropAligner& other);
/// Copy assignment
XdropAligner& operator=(const XdropAligner& other);
/// Move constructor
XdropAligner(XdropAligner&& other);
/// Move assignment
XdropAligner& operator=(XdropAligner&& other);
};
/*
* A dozeu-backed X-drop aligner that uses base qualities to adjust
* alignment scores.
*/
class QualAdjXdropAligner : public DozeuInterface {
public:
/// Main constructor. Expects a 4 x 4 score matrix and a 4 x 4 x 64 quality adjusted matrix
QualAdjXdropAligner(const int8_t* _score_matrix,
const int8_t* _qual_adj_score_matrix,
int8_t _gap_open,
int8_t _gap_extension);
// see DozeuInterface::align and DozeuInterface::align_pinned below for alignment
// interface
private:
// implementations of virtual functions from DozeuInterface
dz_query_s* pack_query_forward(const char* seq, const uint8_t* qual, int8_t full_length_bonus, size_t len);
dz_query_s* pack_query_reverse(const char* seq, const uint8_t* qual, int8_t full_length_bonus, size_t len);
const dz_forefront_s* scan(const dz_query_s* query, const dz_forefront_s** forefronts,
size_t n_forefronts, const char* ref, int32_t rlen, uint32_t rid,
uint16_t xt);
const dz_forefront_s* extend(const dz_query_s* query, const dz_forefront_s** forefronts,
size_t n_forefronts, const char* ref, int32_t rlen,
uint32_t rid, uint16_t xt);
dz_alignment_s* trace(const dz_forefront_s* forefront);
void flush();
public:
QualAdjXdropAligner() = default;
~QualAdjXdropAligner(void);
/// Copy constructor
QualAdjXdropAligner(const QualAdjXdropAligner& other);
/// Copy assignment
QualAdjXdropAligner& operator=(const QualAdjXdropAligner& other);
/// Move constructor
QualAdjXdropAligner(QualAdjXdropAligner&& other);
/// Move assignment
QualAdjXdropAligner& operator=(QualAdjXdropAligner&& other);
};
} // end of namespace vg
#endif // VG_DOZEU_INTERFACE_HPP_INCLUDED
/**
* end of dozeu_interface.hpp
*/
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