# This software is Copyright 2017 The Regents of the University of California. All Rights Reserved. Permission to copy, modify, and distribute this software and its documentation for educational, research and non-profit purposes, without fee, and without a written agreement is hereby granted, provided that the above copyright notice, this paragraph and the following three paragraphs appear in all copies. Permission to make commercial use of this software may be obtained by contacting:
#
# Office of Innovation and Commercialization
#
# University of California
#
# La Jolla, CA 92093-0910
#
# (858) 534-5815
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# invent@ucsd.edu
#
# This software program and documentation are copyrighted by The Regents of the University of California. The software program and documentation are supplied "as is", without any accompanying services from The Regents. The Regents does not warrant that the operation of the program will be uninterrupted or error-free. The end-user understands that the program was developed for research purposes and is advised not to rely exclusively on the program for any reason.
#
# IN NO EVENT SHALL THE UNIVERSITY OF CALIFORNIA BE LIABLE TO ANY PARTY FOR DIRECT, INDIRECT, SPECIAL, INCIDENTAL, OR CONSEQUENTIAL DAMAGES, INCLUDING LOST PROFITS, ARISING OUT OF THE USE OF THIS SOFTWARE AND ITS DOCUMENTATION, EVEN IF THE UNIVERSITY OF CALIFORNIA HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGE. THE UNIVERSITY OF CALIFORNIA SPECIFICALLY DISCLAIMS ANY WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE. THE SOFTWARE PROVIDED HEREUNDER IS ON AN "AS IS" BASIS, AND THE UNIVERSITY OF CALIFORNIA HAS NO OBLIGATIONS TO PROVIDE MAINTENANCE, SUPPORT, UPDATES, ENHANCEMENTS, OR MODIFICATIONS.

#Author: Viraj Deshpande
#Contact: virajbdeshpande@gmail.com


##This is a suite to load reference genome (not just hg19, as filename implies), genes, exons, repeat content and perform operations on this genome, compare variants
## it handles annotations from a database and is not restricted to solely hg19 if global_names.REF is not hg19.

import sys
from bisect import bisect_left
from collections import defaultdict
from time import time
import pysam
import heapq
import copy
import os
import logging

import global_names

REF = global_names.REF
TSTART = global_names.TSTART
print("Global ref name is " + REF)

try:
    DATA_REPO = os.environ["AA_DATA_REPO"]
except:
    logging.warning("#TIME " + '%.3f\t'%(time() - TSTART) + " Unable to set AA_DATA_REPO variable. Setting to working directory")
    DATA_REPO = '.'
if DATA_REPO == '.' or DATA_REPO == '':
    logging.warning("#TIME " + '%.3f\t'%(time() - TSTART) + " AA_DATA_REPO not set or empy. Setting to working directory")
    DATA_REPO = '.'

REF_files = defaultdict(lambda: '', {})
try:
    for l in open(DATA_REPO + '/' + REF + '/file_list.txt'):
        REF_files[l.strip().split()[0]] = l.strip().split()[1]
except:
    logging.warning("#TIME " + '%.3f\t'%(time() - TSTART) + " Unable to find reference in $AA_DATA_REPO/REF/file_list.txt. Setting to empty.")


class fake_fasta(object):
    def fetch(self, a=None, b=0, c=0):
        return ''.join(['N' for i in range(c - b + 1)])
try:
    fa_file = pysam.Fastafile(DATA_REPO + '/' + REF + '/' + REF_files['fa_file'])
except:
    logging.warning("#TIME " + '%.3f\t'%(time() - TSTART) + " Unable to open fasta file: \"" + DATA_REPO + '/' + REF + '/' + REF_files['fa_file'] + "\". Reference sequences will be set to N.")
    fa_file = fake_fasta()

chrLen_filename = DATA_REPO + '/' + REF + '/' + REF_files['chrLen_file']
duke35_filename = DATA_REPO + '/' + REF + '/' + REF_files['duke35_filename']
wgexclude_filename = DATA_REPO + '/' + REF + '/' + REF_files['mapability_exclude_filename']
gene_filename = DATA_REPO + '/' + REF + '/' + REF_files['gene_filename']
exon_filename = DATA_REPO + '/' + REF + '/' + REF_files['exon_file']
oncogene_filename = DATA_REPO + '/' + REF + '/' + REF_files['oncogene_filename']
centromere_filename = DATA_REPO + '/' + REF + '/' + REF_files['centromere_filename']
conserved_regions_filename = DATA_REPO + '/' + REF + '/' + REF_files['conserved_regions_filename']
segdup_filename = DATA_REPO + '/' + REF + '/' + REF_files['segdup_filename']
complementary_nucleotide = defaultdict(lambda: 'N', {'A':'T', 'C':'G', 'G':'C', 'T':'A', 'a':'t', 'c':'g', 'g':'c', 't':'a', 'n':'n', 'N':'N'})
duke35 = []
duke35_exists = [True]

# Handling chromosome names, lengths, sorting, positions and addition of new chromosomes
chr_id = {}
chrName = {}
chromList = [str(x) for x in range(1, 23)] + ['X'+'Y']  # must be updated if including an organism with more chroms.


def chrNum(chrname, mode='append'):
    if chrname in chr_id:
        return chr_id[chrname]
    else:
        if mode == 'init':
            cnum = len(chr_id)
        else:
            cnum = 1000000 + len(chr_id)
        chr_id[chrname] = cnum
        chrName[cnum] = chrname
        return chr_id[chrname]

chrLen = defaultdict(lambda: 0, {})
try:
    for line in open(chrLen_filename):
        ll = line.strip().split()
        chrLen[chrNum(ll[0], mode='init')] = int(ll[1])
except:
    logging.warning("#TIME " + '%.3f\t'%(time() - TSTART) + " Unable to open chromosome lengths file: \"" + chrLen_filename + "\"")

chrOffset = {}
def absPos(chrname, pos=0):
    cnum = chrNum(chrname)
    if chrNum(chrname) not in chrOffset:
        chrkeys = sorted(chrName.keys())
        sumlen = sum([chrLen[c] for c in chrLen if c in chrOffset])
        for i in range(len(chrkeys)):
            if chrkeys[i] not in chrOffset:
                chrOffset[chrkeys[i]] = sumlen
                sumlen += chrLen[chrkeys[i]]
            if cnum < chrkeys[i]:
                break
    return chrOffset[chrNum(chrname)] + pos 

for c in chrLen:
    ap = absPos(chrName[c]) 

def chrPos(abspos):
    for c in chrOffset:
        if chrOffset[c] < abspos and chrOffset[c] + chrLen[c] >= abspos:
            return (chrName[c], abspos - chrOffset[c])
    return None

def update_chrLen(len_list):
    for l in len_list:
        chrLen[chrNum(l[0])] = int(l[1])
    for l in len_list:
        cpos = absPos(l[0], 1)



def reverse_complement(seq):
    return ''.join([complementary_nucleotide[a] for a in seq][::-1])



class interval(object):
    def __init__(self, line, start=-1, end=-1, strand=1,
        file_format='', bamfile=None, info='', exclude_info_string=False):
        self.info = ""
        self.file_format = file_format
        if type(line) == pysam.AlignedRead or type(line) == pysam.AlignedSegment:
            self.load_pysamread(line, bamfile)
        elif start == -1:
            self.load_line(line, file_format, exclude_info_string=exclude_info_string)
        elif end == -1:
            self.load_pos(line, start, start, strand)
        else:
            self.load_pos(line, start, end, strand)
        if len(info) > 0:
            self.info = info

    def load_line(self, line, file_format, exclude_info_string=False):
        if file_format == '':
            if len(line.strip().split()) == 1:
                self.chrom = line.split(':')[0]
                self.start = int(line.split(':')[1].split('-')[0])
                if '-' not in line:
                    self.end = int(line.split(':')[1].split('-')[0])
                else:
                    self.end = int(line.split(':')[1].split('-')[1])
                if self.start < self.end:
                    self.strand = 1
                else:
                    self.strand = -1
                return
            else:
                 file_format = 'bed'
        if file_format=='gff':
            ll = line.strip().split()
            self.chrom = ll[0]
            self.start, self.end = sorted([int(float(ll[3])), int(float(ll[4]))])
            if ll[6] =='+':
                self.strand = 1
            else:
                self.strand = -1
            if not exclude_info_string:
                self.info = {r[0: r.find('=')]: r[r.find('=') + 1: ]
                         for r in ll[8].strip().strip(';').split(';')}
                self.info['Variant'] = ll[5]
        elif file_format == 'bed':        
            ll = line.strip().split()
            self.chrom = ll[0]
            if (REF == "hg19" or REF == "GRCh38" or REF == "mm10" or REF == "GRCm38") and 0 < len(self.chrom) < 3:
                try:
                    ci = int(self.chrom)
                    if 0 < ci < 23:
                        self.chrom = 'chr' + self.chrom
                        logging.info("Corrected chromosome name (appended 'chr') " + self.chrom + " \n")

                except ValueError:
                    if self.chrom in {"M", "X", "Y"}:
                        self.chrom = 'chr' + self.chrom
                    else:
                        logging.warning("Chromosome name " + self.chrom + " may be incompatible")

            self.start, self.end = sorted([int(float(ll[1])), int(float(ll[2]))])
            if int(float(ll[2])) >= int(float(ll[1])):
                self.strand = 1
            else:
                self.strand = -1
            if not exclude_info_string:
                self.info = ll[3:]
        else:
            raise(Exception("Invalid interval format" + str(line)))

    def load_pos(self, chrom, start, end, strand):
        self.chrom = chrom 
        self.start = int(start)
        self.end = int(end)
        self.strand = strand
        if start > end:
            self.start = int(end)
            self.end = int(start)
            self.strand = -1 * strand

    def load_pysamread(self, line, bamfile):
        if bamfile is None:
            raise Exception("Interval of pysam AlignedRead without bamfile")
        self.chrom = line.reference_name
        self.start = line.reference_start
        self.end = 0
        if line.reference_end is not None:
            self.end = line.reference_end
        else:
            logging.warning("Reference_end for " + str(self) + " was NoneType. Setting to 0.")

        if line.is_reverse:
            self.strand = -1
        else:
            self.strand = 1

    def __gt__(self, y):
        if self.chrom != y.chrom:
            return chrNum(self.chrom) > chrNum(y.chrom)
        elif int(self.end) != int(y.end):
            return int(self.end) > int(y.end)
        else:
            return int(self.start) > int(y.start)

    def size(self):
        return self.end - self.start + 1

    def __str__(self):
        if len(str(self.info)) == 0:
            return '\t'.join(map(str, [self.chrom, self.start, self.end]))
        elif type(self.info) == list:
            return '\t'.join(map(str, [self.chrom, self.start, self.end] + list(self.info)))
        elif type(self.info) == dict:
            return '\t'.join(map(str, [self.chrom, self.start, self.end] + [str(s) + '=' + str(self.info[s]) for s in self.info]))
        else:
            return '\t'.join(map(str, [self.chrom, self.start, self.end, self.info]))

    def gc_content(self):
        seq = fa_file.fetch(self.chrom, self.start, self.end)
        # if 'G' in seq:
        #     print seq, seq.count('G'), seq.count('C'), float(seq.count('G') + seq.count('C')) / len(seq)
        #     exit()
        if len(seq) == 0:
            return 0.5
        return float(seq.count('G') + seq.count('C') + seq.count('g') + seq.count('c')) / len(seq)

    def sequence(self, new_fa_file=None):
        if new_fa_file is not None:
            seq = new_fa_file.fetch(self.chrom, self.start, self.end + 1)
        else:
            seq = fa_file.fetch(self.chrom, self.start, self.end + 1)
        if self.strand == 1:
            return seq
        else:
            return ''.join([complementary_nucleotide[a] for a in seq][::-1])

    def intersects(self, n, extend=0, margin=0.0):
        if margin > 0.0:
            if self.intersects(interval(n.chrom, n.start, n.end - (1 - margin) * (n.end - n.start))) and self.intersects(interval(n.chrom, n.start + (1 - margin) * (n.end - n.start)), n.end):
                return True
            else:
                s = self
                if n.intersects(interval(s.chrom, s.start, s.end - (1 - margin) * (s.end - s.start))) and n.intersects(interval(s.chrom, s.start + (1 - margin) * (s.end - s.start)), s.end):
                    return True
            return False
        a = [self.chrom, max(0, self.start - extend), self.end + extend]
        b = [n.chrom, n.start, n.end]
        if (a[0] != b[0]):
            return False
        if (int(a[1])-int(b[1]))*(int(a[2])-int(b[1])) <= 0:
            return True
        if (int(a[1])-int(b[2]))*(int(a[2])-int(b[2])) <= 0:
            return True
        if (int(a[1])-int(b[1]))*(int(a[1])-int(b[2])) <= 0:
            return True
        if (int(a[2])-int(b[1]))*(int(a[2])-int(b[2])) <= 0:
            return True
        return False

    def intersection(self, y):
        if not self.intersects(y):
            return None
        return interval(self.chrom, max(self.start, y.start), min(self.end, y.end))

    def merge(self, y, extend=0):
        if not self.intersects(y, extend):
            return None
        return interval(self.chrom, min(self.start, y.start), max(self.end, y.end))

    def atomize(self, y):
        il = interval_list([self, y])
        il.sort()
        ilr = []
        if il[0].intersects(il[1]):
            ilint = il[0].intersection(il[1])
            if il[0].start < il[1].start:
                ilr.append((interval(il[0].chrom, il[0].start, ilint.start - 1), [il[0]]))
            elif il[1].start < il[0].start:
                ilr.append((interval(il[1].chrom, il[1].start, ilint.start - 1), [il[1]]))
            ilr.append((ilint, il))
            if il[0].end > il[1].end:
                ilr.append((interval(il[0].chrom, ilint.end + 1, il[0].end), [il[0]]))
            elif il[1].end > il[0].end:
                ilr.append((interval(il[1].chrom, ilint.end + 1, il[1].end), [il[1]]))
            return ilr
        else:
            return [(il[0], [il[0]]), (il[1], [il[1]])]

    def contains(self, x, y=-1, z=-1):
        if type(x) == interval:
            if self.intersects(x) and self.intersection(x).size() == x.size():
                return True
            else:
                return False
        if y != -1:
            if z == -1:
                z = y
            if self.intersects(interval(x, y, z)) and self.intersection(interval(x, y, z)).size() == interval(x, y, z).size():
                return True
        return False

    def filter_repeat(self):
        if len(interval_list([self]).intersection(wgexclude)) > 0:
            return True
        if len(interval_list([self]).intersection(conserved_regions)) > 0:
            return True
        if self.rep_content() > 4.5:
            return True
        return False

    def rep_content(self):
        # logging.info("#TIME " + '%.3f\t'%(time() - TSTART) + " rep_content: init ")
        if self.chrom == 'chrM' or self.chrom == 'MT':
            return 5.0
        if self.chrom.strip('chr') not in chromList:
            return 1.0
        s34 = interval(self.chrom, self.start, max(self.start, self.end - 34))
        # logging.info("#TIME " + '%.3f\t'%(time() - TSTART) + " rep_content: to load duke ")
        if duke35_exists[0] and len(duke35) == 0:
            try:
                duke35file = open(duke35_filename)
                duke35.extend([l.strip() for l in duke35file])
                duke35file.close()
            except:
                logging.warning("#TIME " + '%.3f\t'%(time() - TSTART) + " rep_content: Unable to open mapability file \"" + duke35_filename + "\"." )
                duke35_exists[0] = False
                duke35.extend(["chr_Un  0   1   1"])
        # logging.info("#TIME " + '%.3f\t'%(time() - TSTART) + " rep_content: duke loaded")
        ictime = 0
        itime = 0
        hi = len(duke35) - 1
        lo = 0
        numiter = 0
        while hi - lo > 1:
            numiter += 1
            p = (hi + lo) // 2
            ctime = time()
            m = interval(duke35[p])
            ictime += time() - ctime
            ctime = time()
            if s34.intersects(m) or m > s34:
                hi = p
            else:
                lo = p
            itime += time() - ctime
        p = lo
        m = interval(duke35[p])
        sum_duke = 0
        len_duke = 0
        # logging.info("#TIME " + '%.3f\t'%(time() - TSTART) + " rep_content: found " + str(numiter) + " " + str(ictime) + " " + str(itime))
        while s34 > m or s34.intersects(m):
            if not s34.intersects(m):
                p += 1
                if p >= len(duke35) or p <= 0:
                    raise Exception('p index out of range: ' + str(p)+' '+str(lo)+' '+str(self)+' '+str(m) + ' '+str(interval(duke35[lo])))
                m = interval(duke35[p])
                continue
            repc = 5.0 if float(m.info[0]) == 0 else 1.0 / float(m.info[0])
            sum_duke += s34.intersection(m).size() * repc
            len_duke += s34.intersection(m).size()
            p += 1
            if p >= len(duke35):
                break
            m = interval(duke35[p])
        # logging.info("#TIME " + '%.3f\t'%(time() - TSTART) + " rep_content: done")
        # exit()
        if len_duke > 0:
            return sum_duke / len_duke
        else:
            return 1.0

    def num_unmasked(self):
        if self.chrom not in fa_file.references:
            return self.size()
        seq = fa_file.fetch(self.chrom, self.start, self.end)
        return len([c for c in seq if c in 'ACGT'])

    def segdup_uniqueness(self):
        sl = interval_list([self]).intersection(segdup_list)
        slsd = sum([self.intersection(i[1]).size() for i in sl])
        return float(self.size()) / (self.size() + slsd)
    
    def extend(self, extend_len=0):
        return interval(self.chrom, max(0, self.start - extend_len), min(self.end + extend_len, chrLen[chrNum(self.chrom)]), self.strand)


class interval_list(list, object):
    def __init__(self, ilist=None, file_format=None, sort=True, exclude_info_string=False):
        if ilist == None:
            ilist = []
        self.file_format = file_format
        if file_format in ['bed', 'gff']:
            self.bed_to_list(ilist, exclude_info_string=exclude_info_string)
        if file_format is None:
            list.__init__(self,ilist)
        if sort:
            self.sort()
        self.offset = None

    def bed_to_list(self, file_name, exclude_info_string=False):
        if file_name is not None:
            try:
                f = open(file_name)
                list.__init__(self, [interval(l, file_format=self.file_format, exclude_info_string=exclude_info_string)
                              for l in f if len(l.strip().split()) > 2
                              and l.strip()[0] != '#'])
                f.close()
            except:
                logging.error("#TIME " + '%.3f\t'%(time() - TSTART) + " interval_list: Unable to open interval file \"" + file_name + "\"." )


    def merge_clusters(self, extend=0, margin=0.0):
        ml = []
        ci = None
        cl = []
        ai = 0
        cend = len(self)
        for a in self[::-1]:
            ai += 1
            if ci is None or not a.intersects(ci, extend, margin):
                cstart = len(self) - ai + 1
                cl = self[cstart:cend]
                if ci is not None:
                    ml.append((ci, cl))
                ci = a
                cl = []
                cend = len(self) - ai + 1
                # if ai != sum([len(m[1]) for m in ml]) + 1:
                #     print "divergent", ai, str(a)
                #     exit()
            ci = ci.merge(a, extend)
            # cl.append(a)
        cstart = 0
        cl = self[cstart:cend]
        if ci is not None:
            ml.append((ci,cl))
        return ml[::-1]

    def repeats(self, count=1):
        activeq = []
        if activeq is None:
            print("h1")
            exit()
        jinterval = None
        ilist = []
        for a in self[::-1]:
            while len(activeq) > 0 and not a.intersects(activeq[0][1]):
                heapq.heappop(activeq)
                if activeq is None:
                    print("h2")
                    exit()
            if len(activeq) < count and jinterval is not None:
                ilist.append((jinterval, copy.copy(aq)))
                if activeq is None:
                    print("h3")
                    exit()
                jinterval = None
            heapq.heappush(activeq, (-1 * a.start, a))
            if len(activeq) >= count:
                if jinterval is None:
                    jinterval = interval(a.chrom, activeq[0][1].start, a.end)
                    aq = copy.copy(activeq)
                else:
                    jinterval.start = min(jinterval.start, activeq[0][1].start)
                    heapq.heappush(aq, (-1 * a.start, a))
        if jinterval is not None:
            ilist.append((jinterval, copy.copy(aq)))
            jinterval = None
        return ilist[::-1]

    def intersection(self, l2, extend=0):
        si = len(self) - 1
        l2i = len(l2) - 1
        sj = len(self) - 1
        l2j = len(l2) - 1
        il = []
        while si >= 0:
            while l2i >= 0 and l2[l2i] > self[si] and not self[si].intersects(l2[l2i], extend=extend):
                l2i -= 1
            l2j = l2i
            while l2j >= 0 and self[si].intersects(l2[l2j], extend=extend):
                il.append((self[si], l2[l2j]))
                l2j -= 1
            si -= 1
        return il[::-1]

    def atomize(self, h2):
        i = 0
        j = 0
        atomlist = []
        if len(self) > 0:
            c1 = self[0]
        if len(h2) > 0:
            c2 = h2[0]
        c = None
        while i < len(self) or j < len(h2):
            # if c is not None:
            #     print "%%", i, j, str(c[0]), [str(aa) for aa in c[1]], [str(aa[0]) for aa in atomlist]
            # else:
            #     print "%%", i, j, [],  [str(aa[0]) for aa in atomlist]
            if c is not None:
                if i < len(self) and self[i] not in c[1] and (self[i].intersects(c[0], -1) or c[0] > self[i]):
                    atm = self[i].atomize(c[0])
                    atm = [(aa[0], [(lambda x: c[1][0] if x == c[0] else x)(aai) for aai in aa[1]]) for aa in atm]
                    # print "%i", [len(rr[1]) for rr in atm], [str(rr[0]) for rr in atm]
                    c = atm[-1]
                    i += 1
                    atomlist += atm[:-1]
                elif j < len(h2) and h2[j] not in c[1] and (h2[j].intersects(c[0], -1) or c[0] > h2[j]):
                    # print j, str(h2[j]), str(c[0]), c[0] > h2[j]
                    atm = c[0].atomize(h2[j])
                    atm = [(aa[0], [(lambda x: c[1][0] if x == c[0] else x)(aai) for aai in aa[1]]) for aa in atm]
                    # print "%j", [len(rr[1]) for rr in atm], [str(rr[0]) for rr in atm]
                    c = atm[-1]
                    j += 1
                    atomlist += atm[:-1]
                else:
                    atomlist.append(c)
                    # if i < len(self) and self[i] in c[1]:
                    # i += 1
                    # if j < len(h2) and h2[j] in c[1]:
                    # j += 1
                    c = None
            else:
                if i >= len(self):
                    atomlist.append((h2[j], [h2[j]]))
                    j += 1
                elif j >= len(h2):
                    atomlist.append((self[i], [self[i]]))
                    i += 1
                else:
                    atm = self[i].atomize(h2[j])
                    atomlist += atm[:-1]
                    c = atm[-1]
                    # if self[i] not in c[1]:
                    i += 1
                    # if h2[j] not in c[1]:
                    j += 1
        if c is not None:
            atomlist.append(c)
        return atomlist

    def get_repeat_content(self):
        try:
            duke35_file = open(duke35_filename)
            print("counting repeats", time())
            self.sort()
            sum_duke = [0.0 for i in self]
            len_duke = [0.0 for i in self]
            lno = 0
            i = 0
            j = 0
            for line in duke35_file:
                lno += 1
                duke_int = interval(line)
                while not(duke_int.intersects(self[i])) and duke_int > self[i]:
                    i += 1
                if not duke_int.intersects(self[i]) and self[i] > duke_int:
                    continue
                j = i
                repc = 5.0 if float(duke_int.info[0]) == 0 else 1 / float(duke_int.info[0])
                while j < len(self) and self[j].intersects(duke_int):
                    sum_duke[j] += self[j].intersection(duke_int).size() * repc
                    len_duke[j] += self[j].intersection(duke_int).size()
                    j += 1
            duke35_file.close()
            return {self[i]:sum_duke[i] / len_duke[i] for i in range(len(interval_list))}
        except:
            logging.warning("#TIME " + '%.3f\t'%(time() - TSTART) + " get_repeat_content: Unable to open mapability file \"" + duke35_filename + "\"." )
            duke35_exists[0] = False
            duke35.extend(["chr_Un  0   1   1"])
            return {self[i]:1.0 for i in range(len(interval_list))}

    def offsets(self):
        if self.offset is not None:
            return self.offset
        gap = 0.1
        hratio = 0.8

        vlist = [i for i in self if chrNum(i.chrom) >= 100 and i.chrom[:3] != 'chr']
        hlist = [i for i in self if chrNum(i.chrom) < 100 or i.chrom[:3] == 'chr']
        v_count = len([i for i in self if chrNum(i.chrom) >= 100 and i.chrom[:3] != 'chr'])
        h_count = len(self) - v_count
        h_sum = sum([i.size() for i in hlist])
        v_sum = sum([i.size() for i in vlist])

        hK = len([i for i in hlist if i.size() < h_sum * gap / max(1, h_count)])
        hS = sum([i.size() for i in hlist if i.size() > h_sum * gap / max(1, h_count)])
        min_hsize = hS / (max(1, h_count) / gap - hK)
        h_sum = hS + hK * min_hsize
        
        vK = len([i for i in vlist if i.size() < v_sum * gap / max(1, v_count)])
        vS = sum([i.size() for i in vlist if i.size() > v_sum * gap / max(1, v_count)])
        min_vsize = vS / (max(1, v_count) / gap - vK)
        v_sum = vS + vK * min_vsize


        offset = {}

        h_start = 0
        hscale = 1 if v_count == 0 else hratio
        v_start = 0 if h_count == 0 else hratio
        vscale = 1 if h_count == 0 else (1 - hratio)

        hgap = gap / h_count if h_count > 0 else 0
        vgap = gap / v_count if v_count > 0 else 0
        hpos = h_start + (hgap / 2) * hscale
        vpos = v_start + (vgap / 2) * vscale
        for i in hlist:
            isize = max(i.size(), min_hsize)
            offset[i] = (hpos, hpos + ((1 - gap) * isize / h_sum) * hscale)
            hpos = hpos + ((1 - gap) * isize / h_sum + hgap) * hscale
        for i in vlist:
            isize = max(i.size(), min_vsize)
            offset[i] = (vpos, vpos + ((1 - gap) * isize / v_sum) * vscale)
            vpos = vpos + ((1 - gap) * isize / v_sum + vgap) * vscale
        self.offset = offset
        # for i in self:
        #     print str(i), offset[i], i.size(), hgap, h_sum, hscale, gap, hpos, vpos
        # exit()
        return offset

    def xpos(self, chrom, pos):
        offset = self.offsets()
        for i in self:
            if i.intersects(interval(chrom, max(0, pos - 1), pos)):
                o = offset[i]
                return (o[1] * (pos - i.start) + o[0] * (i.end - pos)) / (i.end - i.start)
        return None

    def offset_breaks(self):
        offset = self.offsets()
        gap = 0.1
        hratio = 0.8

        vlist = [i for i in self if chrNum(i.chrom) >= 100 and i.chrom[:3] != 'chr']
        hlist = [i for i in self if chrNum(i.chrom) < 100 or i.chrom[:3] == 'chr']
        v_count = len([i for i in self if chrNum(i.chrom) >= 100 and i.chrom[:3] != 'chr'])
        h_count = len(self) - v_count
        h_sum = sum([i.size() for i in hlist])
        v_sum = sum([i.size() for i in vlist])

        hscale = 1 if v_count == 0 else hratio
        vscale = 1 if h_count == 0 else (1 - hratio)

        hgap = gap / h_count if h_count > 0 else 0
        vgap = gap / v_count if v_count > 0 else 0

        breaks = []
        iprev = None
        for i in self:
            if iprev is None:
                iprev = i
                continue
            if i in hlist and iprev.chrom == i.chrom:
                breaks.append((offset[i][0] - hscale * hgap / 2, ':', i.chrom))
                print(str(i), str(iprev), i in hlist, iprev.chrom == i.chrom)
            elif i in hlist and iprev.chrom != i.chrom:
                breaks.append((offset[i][0] - hscale * hgap / 2, '--', i.chrom))
            elif i in vlist and iprev in hlist:
                breaks.append((offset[i][0] - vscale * vgap / 2, '-', i.chrom))
            elif i in vlist and i.chrom == iprev.chrom:
                breaks.append((offset[i][0] - vscale * vgap / 2, ':', i.chrom))
            else:
                breaks.append((offset[i][0] - vscale * vgap / 2, '--', i.chrom))

            iprev = i
        return breaks

    def __str__(self):
       return str(([str(i) for i in self]))



oncogene_list = interval_list(oncogene_filename, 'gff')
oncogene_list.sort()
gene_list = interval_list(gene_filename, 'gff')



exon_list = interval_list([])
def load_exons():
    if len(exon_list) > 0:
        return
    try:
        exon_file = open(exon_filename)
        exonFields = [interval(j, file_format='gff')
                      for j in exon_file.read().strip().split('\n')
                      if (len(j.strip()) > 0 and j.strip()[0] != '#' and
                          {r.split('=')[0]:r.split('=')[1]
                           for r in j.strip().split()[8].strip(';').split(';')
                          }['color'] == '000080')]
        exon_file.close()
        exon_list.extend((exonFields))
    except:
        logging.warning("#TIME " + '%.3f\t'%(time() - TSTART) + "unable to load exon file: \"" + exon_filename + "\"")

conserved_regions = interval_list(conserved_regions_filename, 'bed')
conserved_regions.sort()

wgexclude = interval_list(wgexclude_filename, 'bed')
wgexclude.sort()

centromere_list = interval_list(centromere_filename, 'bed')
centromere_list.sort()
centromere_list = interval_list([i[0] for i in centromere_list.merge_clusters(extend=1)])


segdup_list = interval_list(segdup_filename, 'bed')
segdup_list.sort()


