MOIP.cpp
20.5 KB
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#include "MOIP.h"
#include <algorithm>
#include <boost/format.hpp>
#include <cfloat>
#include <cmath>
#include <cstdlib>
#include <fstream>
#include <iostream>
#include <limits>
#include <stdexcept>
#include <utility>
#include <vector>
using std::abs;
using std::cerr;
using std::cout;
using std::endl;
using std::make_pair;
using std::vector;
char MOIP::obj_function_nbr_ = 'A';
uint MOIP::obj_to_solve_ = 1;
double MOIP::precision_ = 1e-5;
bool MOIP::allow_pk_ = true;
uint MOIP::max_sol_nbr_ = 500;
unsigned getNumConstraints(IloModel& m)
{
unsigned count = 0;
IloModel::Iterator iter(m);
while (iter.ok()) {
if ((*iter).asConstraint().getImpl()) ++count;
++iter;
}
return count;
}
MOIP::MOIP() {}
MOIP::MOIP(const RNA& rna, const vector<Motif>& insertionSites, float theta, bool verbose)
: verbose_{verbose}, rna_(rna), insertion_sites_(insertionSites)
{
if (verbose_) cout << "Summary of basepair probabilities:" << endl;
if (verbose_) rna_.print_basepair_p_matrix(theta);
if (verbose_) cout << "Defining problem decision variables..." << endl;
basepair_dv_ = IloNumVarArray(env_);
insertion_dv_ = IloNumVarArray(env_);
// Add the y^u_v decision variables
if (verbose_) cout << "\t>Legal basepairs : ";
uint u, v, c = 0;
index_of_yuv_ = vector<vector<size_t>>(rna_.get_RNA_length() - 6, vector<size_t>(0));
for (u = 0; u < rna_.get_RNA_length() - 6; u++)
for (v = u + 4; v < rna_.get_RNA_length(); v++) // A basepair is possible iff v > u+3
if (rna_.get_pij(u, v) > theta) {
if (verbose_) cout << u << '-' << v << " ";
index_of_yuv_[u].push_back(c);
c++;
char name[15];
sprintf(name, "y%d,%d", u, v);
basepair_dv_.add(IloNumVar(env_, 0, 1, IloNumVar::Bool, name)); // A boolean whether u and v are paired
} else {
index_of_yuv_[u].push_back(rna_.get_RNA_length() * rna_.get_RNA_length() + 1);
}
if (verbose_) cout << endl;
// Purge the list of insertion sites : remove those that are forbidden because bounding basepairs are forbidden
if (verbose_) cout << "\t>Checking insertion sites..." << endl;
vector<uint> to_remove;
for (size_t i = 0; i < insertion_sites_.size(); i++) {
Motif& x = insertion_sites_[i];
if (verbose_) cout << "\t\tbasepair (" << x.comp[0].pos.first << ',' << x.comp.back().pos.second;
if (allowed_basepair(x.comp[0].pos.first, x.comp.back().pos.second) > 0) {
if (verbose_) cout << ") is allowed" << endl;
} else if (!to_remove.size() or (to_remove.size() and to_remove.back() != i)) {
if (verbose_) cout << ") is not allowed, removing motif " << i << " from candidates" << endl;
to_remove.push_back(i);
continue;
} else {
if (verbose_) cout << ") is not allowed (and motif has been previously forbidden)" << endl;
}
if (x.comp.size() == 1) // This constraint is for multi-component motives.
continue;
for (size_t j = 0; j < x.comp.size() - 1; j++) {
if (verbose_) cout << "\t\tbasepair (" << x.comp[j].pos.second << ',' << x.comp[j + 1].pos.first;
if (allowed_basepair(x.comp[j].pos.second, x.comp[j + 1].pos.first) > 0) {
if (verbose_) cout << ") is allowed" << endl;
} else if (!to_remove.size() or (to_remove.size() and to_remove.back() != i)) {
if (verbose_) cout << ") is not allowed, removing motif " << i << " from candidates" << endl;
to_remove.push_back(i);
} else {
if (verbose_) cout << ") is not allowed (and motif has been previously forbidden)" << endl;
}
}
}
for (vector<uint>::reverse_iterator i = to_remove.rbegin(); i != to_remove.rend(); ++i)
insertion_sites_.erase(insertion_sites_.begin() + (*i));
// Add the Cx,i,p decision variables
if (verbose_) cout << "\t>Allowed candidate insertion sites:" << endl;
index_of_first_components.reserve(insertionSites.size());
index_of_Cxip_.reserve(insertionSites.size());
size_t i = 0;
for (uint p = 0; p < insertion_sites_.size(); ++p) {
const Motif& m = insertion_sites_[p];
if (verbose_) cout << "\t\t>" << m.get_identifier() << '\t' << m.pos_string() << endl;
index_of_first_components.push_back(i);
index_of_Cxip_.push_back(vector<size_t>(0));
for (const Component cmp : m.comp) {
index_of_Cxip_.back().push_back(i);
i++;
char name[20];
sprintf(
name,
"C%d,%d-%d",
static_cast<int>(index_of_Cxip_.size() - 1),
static_cast<int>(index_of_Cxip_.back().size() - 1),
cmp.pos.first);
insertion_dv_.add(IloNumVar(env_, 0, 1, IloNumVar::Bool, name)); // A boolean whether component i of motif x is inserted at position p
}
}
if (verbose_) cout << c << " + " << i << " (yuv + Cpxi) decision variables are used." << endl;
// Adding the problem's constraints
model_ = IloModel(env_);
define_problem_constraints();
if (verbose_) cout << "A total of " << getNumConstraints(model_) << " constraints are used." << endl;
// if (getNumConstraints(model_) > 1500) {
// cerr << "\033[31m Quitting because too hard for me (too many constraints). Srry. \033[0m" << endl;
// exit(1);
// }
// if (getNumConstraints(model_) > 2000) {
// cerr << "\033[31mStopping 'cause too big for me...\033[0m" << endl;
// exit(-1);
// }
// Define the motif objective function:
obj1 = IloExpr(env_);
for (uint i = 0; i < insertion_sites_.size(); i++) {
IloNum sum_k = 0;
switch (obj_function_nbr_) {
case 'A':
// RNA MoIP style
for (const Component& c : insertion_sites_[i].comp) sum_k += c.k;
obj1 += IloNum(sum_k * sum_k) * insertion_dv_[index_of_first_components[i]];
break;
case 'B':
// everything but the Jar3D/Bayespairing score
for (const Component& c : insertion_sites_[i].comp) sum_k += c.k;
obj1 += IloNum(insertion_sites_[i].comp.size() / log2(sum_k)) * insertion_dv_[index_of_first_components[i]];
break;
case 'C':
// Weighted by the JAR3D or BayesPairing score only:
obj1 += IloNum(insertion_sites_[i].score_) * insertion_dv_[index_of_first_components[i]];
break;
case 'D':
// everything
for (const Component& c : insertion_sites_[i].comp) sum_k += c.k;
obj1 += IloNum(insertion_sites_[i].comp.size() * insertion_sites_[i].score_ / log2(sum_k)) *
insertion_dv_[index_of_first_components[i]];
break;
}
}
// Define the expected accuracy objective function:
obj2 = IloExpr(env_);
for (size_t u = 0; u < rna_.get_RNA_length() - 6; u++) {
for (size_t v = u + 4; v < rna_.get_RNA_length(); v++) {
if (allowed_basepair(u, v)) obj2 += (IloNum(rna_.get_pij(u, v)) * y(u, v));
}
}
}
MOIP::~MOIP() { env_.end(); }
bool MOIP::is_undominated_yet(const SecondaryStructure& s)
{
for (SecondaryStructure& x : pareto_) {
if (x > s) return false;
}
return true;
}
SecondaryStructure MOIP::solve_objective(int o, double min, double max)
{
// Solves one of the objectives, under constraint that the other should be in [min, max]
if (min > max) {
// variable swap without a third, just because i want to look clever
max = min + max;
min = max - min;
max = max - min;
}
// impose the bounds and the objective
IloObjective obj;
IloRange bounds;
switch (o) {
case 1:
obj = IloMaximize(env_, obj1);
bounds = IloRange(env_, min, obj2, max);
break;
case 2:
obj = IloMaximize(env_, obj2);
bounds = IloRange(env_, min, obj1, max);
break;
}
model_.add(obj);
model_.add(bounds);
IloCplex cplex_ = IloCplex(model_);
cplex_.setOut(env_.getNullStream());
// cplex_.exportModel("latestmodel.lp")
if (!cplex_.solve()) {
if (verbose_) cout << "\t>Failed to optimize LP: no more solutions to find." << endl;
// Removing the objective from the model_
model_.remove(obj);
model_.remove(bounds);
return SecondaryStructure(true);
}
if (verbose_)
cout << "\t>Solution status: objective values (" << cplex_.getValue(obj1) << ", " << cplex_.getValue(obj2) << ')';
// Build a secondary Structure
SecondaryStructure best_ss = SecondaryStructure(rna_);
// if (verbose_) cout << "\t\t>retrieveing motifs inserted in the result secondary structure..." << endl;
for (size_t i = 0; i < insertion_sites_.size(); i++)
// A constraint requires that all the components are inserted or none, so testing the first is enough:
if (cplex_.getValue(insertion_dv_[index_of_first_components[i]]) > 0.5)
best_ss.insert_motif(insertion_sites_[i]);
// if (verbose_) cout << "\t\t>retrieving basepairs of the result secondary structure..." << endl;
for (size_t u = 0; u < rna_.get_RNA_length() - 6; u++)
for (size_t v = u + 4; v < rna_.get_RNA_length(); v++)
if (allowed_basepair(u, v))
if (cplex_.getValue(y(u, v)) > 0.5) best_ss.set_basepair(u, v);
best_ss.sort(); // order the basepairs in the vector
best_ss.set_objective_score(2, cplex_.getValue(obj2));
best_ss.set_objective_score(1, cplex_.getValue(obj1));
// if (verbose_) cout << "\t\t>building the IP forbidding condition..." << endl;
// Forbidding to find best_ss later
IloExpr c(env_);
for (uint d = 0; d < insertion_dv_.getSize(); d++)
if (cplex_.getValue(insertion_dv_[d]) > 0.5)
c += IloNum(1) - insertion_dv_[d];
else
c += insertion_dv_[d];
for (uint d = 0; d < basepair_dv_.getSize(); d++)
if (cplex_.getValue(basepair_dv_[d]) > 0.5)
c += IloNum(1) - basepair_dv_[d];
else
c += basepair_dv_[d];
model_.add(c >= IloNum(1));
// exit
model_.remove(bounds);
model_.remove(obj);
return best_ss;
}
void MOIP::define_problem_constraints(void)
{
// ensure there only is 0 or 1 pairing by nucleotide:
if (verbose_) cout << "\t>ensuring there are at most 1 pairing by nucleotide..." << endl;
uint u, v, count;
uint n = rna_.get_RNA_length();
for (u = 0; u < n; u++) {
count = 0;
IloExpr c1(env_);
for (v = 0; v < u; v++)
if (allowed_basepair(v, u)) {
c1 += y(v, u);
count++;
}
for (v = u + 4; v < n; v++)
if (allowed_basepair(u, v)) {
c1 += y(u, v);
count++;
}
if (count > 1) {
model_.add(c1 <= 1);
if (verbose_) cout << "\t\t" << (c1 <= 1) << endl;
}
}
// forbid lonely basepairs
if (verbose_) cout << "\t>forbidding lonely basepairs..." << endl;
for (u = 0; u < n - 5; u++)
for (v = u + 4; v < n; v++) {
if (allowed_basepair(u, v)) {
IloExpr c2(env_);
c2 += -y(u, v);
if (allowed_basepair(u - 1, v + 1)) c2 += y(u - 1, v + 1);
if (allowed_basepair(u + 1, v - 1)) c2 += y(u + 1, v - 1);
model_.add(c2 >= 0);
if (verbose_) cout << "\t\t" << (c2 >= 0) << endl;
}
}
// Forbid pairings inside every motif component if included
if (verbose_) cout << "\t>forbidding basepairs inside included motif's components..." << endl;
for (size_t i = 0; i < insertion_sites_.size(); i++) {
Motif& x = insertion_sites_[i];
for (size_t j = 0; j < x.comp.size(); j++) {
Component& c = x.comp[j];
IloExpr c3(env_);
IloNum kxi = IloNum(c.k);
c3 += (kxi - IloNum(2)) * C(i, j);
uint count = 0;
for (u = c.pos.first + 1; u < c.pos.second; u++) {
for (v = 0; v < n; v++)
if (allowed_basepair(u, v)) {
c3 += y(u, v);
count++;
}
}
if (count > 0) {
model_.add(c3 <= (kxi - IloNum(2)));
if (verbose_) cout << "\t\t";
if (verbose_) cout << x.get_identifier() << '-' << j << ": ";
if (verbose_) cout << (c3 <= (kxi - IloNum(2))) << endl;
}
}
}
// Forbid component overlap
if (verbose_) cout << "\t>forbidding component overlap..." << endl;
for (u = 0; u < n; u++) {
IloExpr c4(env_);
uint nterms = 0;
for (size_t i = 0; i < insertion_sites_.size(); i++) {
Motif& x = insertion_sites_[i];
for (size_t j = 0; j < x.comp.size(); j++) {
Component& c = x.comp[j];
if (u >= c.pos.first and u <= c.pos.second) { // Cxip contains u
c4 += C(i, j);
nterms++;
}
}
}
if (nterms > 1) {
model_.add(c4 <= 1);
if (verbose_) cout << "\t\t" << (c4 <= 1) << endl;
}
}
// Component completeness
if (verbose_) cout << "\t>ensuring that motives cannot be partially included..." << endl;
for (size_t i = 0; i < insertion_sites_.size(); i++) {
Motif& x = insertion_sites_[i];
if (x.comp.size() == 1) // This constraint is for multi-component motives.
continue;
IloExpr c5(env_);
IloNum jm1 = IloNum(x.comp.size() - 1);
for (size_t j = 1; j < x.comp.size(); j++) {
c5 += C(i, j);
}
model_.add(c5 == jm1 * C(i, 0));
if (verbose_) cout << "\t\t>motif " << i << " : " << (c5 == jm1 * C(i, 0)) << endl;
}
// Force basepairs between the end of a component and the beginning of the next
if (verbose_) cout << "\t>forcing basepairs between bounds of inserted components..." << endl;
for (size_t i = 0; i < insertion_sites_.size(); i++) {
Motif& x = insertion_sites_[i];
IloExpr c6p = IloExpr(env_);
if (allowed_basepair(x.comp[0].pos.first, x.comp.back().pos.second))
c6p += y(x.comp[0].pos.first, x.comp.back().pos.second);
if (verbose_) cout << "\t\t" << (C(i, 0) <= c6p) << endl;
model_.add(C(i, 0) <= c6p);
if (x.comp.size() == 1) // This constraint is for multi-component motives.
continue;
for (size_t j = 0; j < x.comp.size() - 1; j++) {
IloExpr c6 = IloExpr(env_);
if (allowed_basepair(x.comp[j].pos.second, x.comp[j + 1].pos.first))
c6 += y(x.comp[j].pos.second, x.comp[j + 1].pos.first);
model_.add(C(i, j) <= c6);
if (verbose_) cout << "\t\t" << (C(i, j) <= c6) << endl;
}
}
// Forbid pseudoknots
if (!this->allow_pk_) {
if (verbose_) cout << "\t>forbidding pseudoknots..." << endl;
for (size_t u = 0; u < n - 6; u++)
for (size_t v = u + 4; v < n - 1; v++)
if (allowed_basepair(u, v))
for (size_t k = u + 1; k < v; ++k)
for (size_t l = v + 1; l < n; ++l)
if (allowed_basepair(k, l)) {
IloExpr c(env_);
c += y(u, v);
c += y(k, l);
model_.add(c <= 1);
if (verbose_) cout << "\t\t" << (c <= 1) << endl;
}
}
}
void MOIP::search_between(double lambdaMin, double lambdaMax)
{
SecondaryStructure s = solve_objective(obj_to_solve_, lambdaMin, lambdaMax);
if (!s.is_empty_structure) { // A solution has been found
// if the solution is dominated, ignore it
if (!is_undominated_yet(s)) {
if (verbose_) cout << ", but structure is dominated." << endl;
return;
}
// adding the SecondaryStructure s to the set pareto_
if (verbose_) cout << ", not dominated." << endl;
add_solution(s);
// check if some labels should be updated on the vertical
if (exists_vertical_outdated_labels(s))
for (vector<SecondaryStructure>::iterator x = pareto_.end() - 2; x >= pareto_.begin(); x--)
if (
abs(x->get_objective_score(obj_to_solve_) - s.get_objective_score(obj_to_solve_)) < precision_ and
precision_ < s.get_objective_score(3 - obj_to_solve_) - x->get_objective_score(3 - obj_to_solve_)) {
if (verbose_)
cout << "\t>removing structure from Pareto set, obj " << 3 - obj_to_solve_ << " = "
<< x->get_objective_score(3 - obj_to_solve_) << endl;
pareto_.erase(x);
}
// search on top
double min = s.get_objective_score(3 - obj_to_solve_) + precision_;
double max = lambdaMax;
if (verbose_)
cout << std::setprecision(-log10(precision_) + 4) << "\nSolving objective function " << obj_to_solve_
<< ", on top of " << s.get_objective_score(3 - obj_to_solve_) << ": Obj" << 3 - obj_to_solve_
<< " being in [" << std::setprecision(-log10(precision_) + 4) << min << ", "
<< std::setprecision(-log10(precision_) + 4) << max << "]..." << endl;
search_between(min, max);
if (std::abs(max - min) - precision_ > precision_) {
// search below
min = lambdaMin;
max = s.get_objective_score(3 - obj_to_solve_);
if (verbose_)
cout << std::setprecision(-log10(precision_) + 4) << "\nSolving objective function " << obj_to_solve_
<< ", below (or eq. to) " << max << ": Obj" << 3 - obj_to_solve_ << " being in ["
<< std::setprecision(-log10(precision_) + 4) << min << ", "
<< std::setprecision(-log10(precision_) + 4) << max << "]..." << endl;
search_between(min, max);
}
} else {
if (verbose_) cout << "\t>no solutions found." << endl;
}
}
bool MOIP::exists_vertical_outdated_labels(const SecondaryStructure& s) const
{
bool result = false;
for (auto x : pareto_)
if (x != s and abs(x.get_objective_score(obj_to_solve_) - s.get_objective_score(obj_to_solve_)) < precision_)
result = true;
if (result)
for (auto x : pareto_)
if (
x != s and abs(x.get_objective_score(1) - s.get_objective_score(1)) < precision_ and
abs(x.get_objective_score(2) - s.get_objective_score(2)) < precision_)
result = false;
return result;
}
bool MOIP::exists_horizontal_outdated_labels(const SecondaryStructure& s) const
{
bool result = false;
for (auto x : pareto_)
if (x != s and abs(x.get_objective_score(3 - obj_to_solve_) - s.get_objective_score(3 - obj_to_solve_)) < precision_)
result = true;
if (result)
for (auto x : pareto_)
if (
x != s and abs(x.get_objective_score(1) - s.get_objective_score(1)) < precision_ and
abs(x.get_objective_score(2) - s.get_objective_score(2)) < precision_)
result = false;
return result;
}
void MOIP::add_solution(const SecondaryStructure& s)
{
if (verbose_) cout << "\t>adding structure to Pareto set :\t" << s.to_string() << endl;
pareto_.push_back(s);
if (pareto_.size() > max_sol_nbr_) {
cerr << "\033[31m Quitting because combinatorial issues (>" << max_sol_nbr_ << " solutions in Pareto set). \033[0m" << endl;
exit(1);
}
}
size_t MOIP::get_yuv_index(size_t u, size_t v) const
{
size_t a, b;
a = (u < v) ? u : v;
b = (u > v) ? u : v;
return index_of_yuv_[a][b - 4 - a];
}
size_t MOIP::get_Cpxi_index(size_t x_i, size_t i_on_j) const { return index_of_Cxip_[x_i][i_on_j]; }
bool MOIP::allowed_basepair(size_t u, size_t v) const
{
size_t a, b;
a = (v > u) ? u : v;
b = (v > u) ? v : u;
if (b - a < 4) return false;
if (a >= rna_.get_RNA_length() - 6) return false;
if (b >= rna_.get_RNA_length()) return false;
if (get_yuv_index(a, b) == rna_.get_RNA_length() * rna_.get_RNA_length() + 1)
return false; // not allowed because proba < theta
return true;
}
void MOIP::remove_solution(uint i) { pareto_.erase(pareto_.begin() + i); }