geney 1.1.14__py2.py3-none-any.whl → 1.1.15__py2.py3-none-any.whl

geney/immune_utils.py

@@ -2,6 +2,8 @@ import subprocess
 import logging
 import tempfile
 from geney import config_setup
+import re
+from io import StringIO
 import pandas as pd
 
 
@@ -37,17 +39,17 @@ class NetChop(object):
                 logging.error("Error calling netChop: %s:\n%s" % (e, e.output))
                 raise
         parsed = self.parse_netchop(output)
-        return parsed
+        # return parsed
         #
-        # assert len(parsed) == len(sequences), \
-        #     "Expected %d results but got %d" % (
-        #         len(sequences), len(parsed))
-        # assert [len(x) for x in parsed] == [len(x) for x in sequences]
-        # filtered_proteosomes = []
-        # for scores, seq in list(zip(parsed, sequences)):
-        #     proteosome = self.chop_protein(seq, [s > threshold for s in scores])
-        #     filtered_proteosomes.append([e for e in proteosome if len(e) > min_len])
-        # return filtered_proteosomes
+        assert len(parsed) == len(sequences), \
+            "Expected %d results but got %d" % (
+                len(sequences), len(parsed))
+        assert [len(x) for x in parsed] == [len(x) for x in sequences]
+        filtered_proteosomes = []
+        for scores, seq in list(zip(parsed, sequences)):
+            proteosome = self.chop_protein(seq, [s > threshold for s in scores])
+            filtered_proteosomes.append([e for e in proteosome if len(e) > min_len])
+        return filtered_proteosomes
     @staticmethod
     def parse_netchop(netchop_output):
         """
@@ -99,10 +101,6 @@ class NetChop(object):
         return pd.DataFrame(cut_sequences)
 
 
-import re
-import StringIO
-import pandas as pd
-
 def run_mhc(sequences):
     with tempfile.NamedTemporaryFile(dir='/tamir2/nicolaslynn/temp', suffix=".pep", mode="w") as input_fd:
         for (i, sequence) in enumerate(sequences):

geney/oncosplice.py

@@ -530,8 +530,8 @@ class Transcript:
         for i, j in self.exons_pos:
             rel_start, rel_end = pre_indices_pos.index(i), pre_indices_pos.index(j)
             mature_mrna_pos += pre_seq_pos[rel_start:rel_end + 1]
-            pre_indices_pos.extend(pre_indices_pos[rel_start:rel_end + 1])
-        return mature_mrna_pos, pre_indices_pos
+            mature_indices_pos.extend(pre_indices_pos[rel_start:rel_end + 1])
+        return mature_mrna_pos, mature_indices_pos
 
     def generate_mature_mrna(self, inplace=True):
         if inplace:

geney/oncosplice_mouse.py

@@ -0,0 +1,277 @@
+from geney.oncosplice import *
+from copy import deepcopy
+import pandas as pd
+import numpy as np
+from geney.Fasta_segment import Fasta_segment
+import torch
+
+config_setup = { "BASE": "/tamir2/nicolaslynntest/experimental/oncosplice_mouse",
+                 "ONCOSPLICE": "/tamir2/nicolaslynntest/experimental/oncosplice_mouse/oncosplice",
+                 "CHROM_SOURCE": "/tamir2/nicolaslynntest/experimental/oncosplice_mouse/chromosomes",
+                 "MRNA_PATH": "/tamir2/nicolaslynntest/experimental/oncosplice_mouse/annotations",
+                 "MISSPLICING_PATH": "/tamir2/nicolaslynntest/experimental/oncosplice_mouse/missplicing"}
+
+
+from pkg_resources import resource_filename
+from pangolin.model import *
+
+
+IN_MAP = np.asarray([[0, 0, 0, 0],
+                     [1, 0, 0, 0],
+                     [0, 1, 0, 0],
+                     [0, 0, 1, 0],
+                     [0, 0, 0, 1]])
+INDEX_MAP = {0:1, 1:2, 2:4, 3:5, 4:7, 5:8, 6:10, 7:11}
+model_nums = [1, 3, 5, 7]
+
+models = []
+for i in model_nums:
+    for j in range(1, 6):
+        model = Pangolin(L, W, AR)
+        if torch.cuda.is_available():
+            model.cuda()
+            weights = torch.load(resource_filename("pangolin","models/final.%s.%s.3" % (j, i)))
+        else:
+            weights = torch.load(resource_filename("pangolin","models/final.%s.%s.3" % (j, i)),
+                                 map_location=torch.device('cpu'))
+        model.load_state_dict(weights)
+        model.eval()
+        models.append(model)
+
+def one_hot_encode(seq, strand='+'):
+    seq = seq.upper().replace('A', '1').replace('C', '2')
+    seq = seq.replace('G', '3').replace('T', '4').replace('N', '0')
+    if strand == '+':
+        seq = np.asarray(list(map(int, list(seq))))
+    elif strand == '-':
+        seq = np.asarray(list(map(int, list(seq[::-1]))))
+        seq = (5 - seq) % 5  # Reverse complement
+    return IN_MAP[seq.astype('int8')]
+
+
+def run_pangolin_seq(seq):
+    seq = one_hot_encode(seq, '+').T
+    seq = torch.from_numpy(np.expand_dims(seq, axis=0)).float()
+
+    if torch.cuda.is_available():
+        seq = seq.to(torch.device("cuda"))
+
+    score = []
+    for j, model_num in enumerate(model_nums):
+        # score = []
+        # Average across 5 models
+        for model in models[5*j:5*j+5]:
+            with torch.no_grad():
+                score.append(model(seq)[0][INDEX_MAP[model_num],:].cpu().numpy())
+    return np.mean(score, axis=0)
+
+# Missplicing Detection
+def find_ss_changes(ref_dct, mut_dct, known_splice_sites, threshold=0.5):
+    '''
+    :param ref_dct:  the spliceai probabilities for each nucleotide (by genomic position) as a dictionary for the reference sequence
+    :param mut_dct:  the spliceai probabilities for each nucleotide (by genomic position) as a dictionary for the mutated sequence
+    :param known_splice_sites: the indices (by genomic position) that serve as known splice sites
+    :param threshold: the threshold for detection (difference between reference and mutated probabilities)
+    :return: two dictionaries; discovered_pos is a dictionary containing all the positions that meat the threshold for discovery
+            and deleted_pos containing all the positions that meet the threshold for missing and the condition for missing
+    '''
+
+    new_dict = {v: mut_dct.get(v, 0) - ref_dct.get(v, 0) for v in
+                list(set(list(ref_dct.keys()) + list(mut_dct.keys())))}
+
+    discovered_pos = {k: {'delta': round(float(v), 3), 'absolute': round(float(mut_dct[k]), 3)} for k, v in
+                      new_dict.items() if v >= threshold and k not in known_splice_sites}   # if (k not in known_splice_sites and v >= threshold) or (v > 0.45)}
+
+    deleted_pos = {k: {'delta': round(float(v), 3), 'absolute': round(float(mut_dct.get(k, 0)), 3)} for k, v in
+                   new_dict.items() if -v >= threshold and k in known_splice_sites}      #if k in known_splice_sites and v <= -threshold}
+
+    return discovered_pos, deleted_pos
+
+
+def run_pangolin_comparison(mutations, transcript_data, sai_mrg_context=5000, min_coverage=2500, sai_threshold=0.5):
+    positions = mutations.positions
+    end_positions = [m.start + len(m.ref) for m in mutations.variants]
+    positions.extend(end_positions)
+
+    seq_start_pos = min(positions) - sai_mrg_context - min_coverage
+    seq_end_pos = max(positions) + sai_mrg_context + min_coverage
+
+    fasta_obj = Fasta_segment()
+    ref_seq, ref_indices = fasta_obj.read_segment_endpoints(
+        config_setup['CHROM_SOURCE'] / f'chr{mutations.chrom}.fasta',
+        seq_start_pos,
+        seq_end_pos)
+
+    transcript_start, transcript_end, rev = transcript_data.transcript_lower, transcript_data.transcript_upper, transcript_data.rev
+
+    start_pad = ref_indices.index(transcript_start) if transcript_start in ref_indices else 0
+    end_cutoff = ref_indices.index(transcript_end) if transcript_end in ref_indices else len(ref_indices)
+    end_pad = len(ref_indices) - end_cutoff
+    ref_seq = 'N' * start_pad + ref_seq[start_pad:end_cutoff] + 'N' * end_pad
+    ref_indices = [-1] * start_pad + ref_indices[start_pad:end_cutoff] + [-1] * end_pad
+    mut_seq, mut_indices = ref_seq, ref_indices
+
+    for mut in mutations:
+        mut_seq, mut_indices = generate_mut_variant(seq=mut_seq, indices=mut_indices, mut=mut)
+
+    ref_indices = ref_indices[sai_mrg_context:-sai_mrg_context]
+    mut_indices = mut_indices[sai_mrg_context:-sai_mrg_context]
+
+    visible_donors = np.intersect1d(transcript_data.donors, ref_indices)
+    visible_acceptors = np.intersect1d(transcript_data.acceptors, ref_indices)
+
+    if rev:
+        ref_seq = reverse_complement(ref_seq)
+        mut_seq = reverse_complement(mut_seq)
+        ref_indices = ref_indices[::-1]
+        mut_indices = mut_indices[::-1]
+
+    ref_seq_probs = run_pangolin_seq(ref_seq)
+    mut_seq_probs = run_pangolin_seq(mut_seq)
+
+
+    assert len(ref_indices) == len(ref_seq_probs), 'Reference pos not the same'
+    assert len(mut_indices) == len(mut_seq_probs), 'Mut pos not the same'
+
+    iap, dap = find_ss_changes({p: v for p, v in list(zip(ref_indices, ref_seq_probs))},
+                               {p: v for p, v in list(zip(mut_indices, mut_seq_probs))},
+                               visible_acceptors,
+                               threshold=sai_threshold)
+
+
+    idp, ddp = find_ss_changes({p: v for p, v in list(zip(ref_indices, ref_seq_probs))},
+                               {p: v for p, v in list(zip(mut_indices, mut_seq_probs))},
+                               visible_donors,
+                               threshold=sai_threshold)
+
+
+    ref_acceptors = {a: b for a, b in list(zip(ref_indices, ref_seq_probs))}
+    ref_donors = {a: b for a, b in list(zip(ref_indices, ref_seq_probs))}
+
+    lost_acceptors = {int(p): {'absolute': np.float64(0), 'delta': round(float(-ref_acceptors[p]), 3)} for p in visible_acceptors if p not in mut_indices and p not in dap}
+    lost_donors = {int(p): {'absolute': np.float64(0), 'delta': round(float(-ref_donors[p]), 3)} for p in visible_donors if p not in mut_indices and p not in ddp}
+    dap.update(lost_acceptors)
+    ddp.update(lost_donors)
+
+    missplicing = {'missed_acceptors': dap, 'missed_donors': ddp, 'discovered_acceptors': iap, 'discovered_donors': idp}
+    missplicing = {outk: {float(k): v for k, v in outv.items()} for outk, outv in missplicing.items()}
+    return {outk: {int(k) if k.is_integer() else k: v for k, v in outv.items()} for outk, outv in missplicing.items()}
+
+
+class PredictPangolin:
+    def __init__(self, mutation, gene_data,
+                threshold=0.5, context=5000, coverage=2500):
+        self.modification = mutation
+        self.threshold = threshold
+        self.transcript_id = gene_data.transcript_id
+        self.spliceai_db = config_setup['MISSPLICING_PATH'] / f'spliceai_epistatic'
+        self.missplicing = {}
+        self.missplicing = run_pangolin_comparison(self.modification, transcript_data=gene_data, sai_mrg_context=context, min_coverage=coverage, sai_threshold=0.1)
+
+
+    def __repr__(self):
+        return f'Missplicing({self.modification.mut_id}) --> {self.missplicing}'
+
+    def __str__(self):
+        return self.aberrant_splicing
+    def __bool__(self):
+        for event, details in self.aberrant_splicing.items():
+            if details:
+                return True
+        return False
+
+    def __eq__(self, alt_splicing):
+        flag, _ = check_splicing_difference(self.missplicing, alt_splicing, self.threshold)
+        return not flag
+
+    def __iter__(self):
+        penetrances = [abs(d_in['delta']) for d in self.missplicing.values() for d_in in d.values()] + [0]
+        return iter(penetrances)
+
+    @property
+    def aberrant_splicing(self):
+        return self.apply_sai_threshold(self.missplicing, self.threshold)
+
+    def apply_sai_threshold(self, splicing_dict=None, threshold=None):
+        splicing_dict = self.missplicing if not splicing_dict else splicing_dict
+        threshold = self.threshold if not threshold else threshold
+        new_dict = {}
+        for event, details in splicing_dict.items():
+            for e, d in details.items():
+                if abs(d['delta']) >= threshold:
+                    return splicing_dict
+        return new_dict
+
+
+    def apply_sai_threshold_primary(self, splicing_dict=None, threshold=None):
+        splicing_dict = self.missplicing if not splicing_dict else splicing_dict
+        threshold = self.threshold if not threshold else threshold
+        new_dict = {}
+        for event, details in splicing_dict.items():
+            new_dict_in = {}
+            for e, d in details.items():
+                if abs(d['delta']) >= threshold:
+                    new_dict_in[e] = d
+            new_dict[event] = new_dict_in
+        return new_dict
+
+    def get_max_missplicing_delta(self):
+        max_delta = 0
+        for event, details in self.missplicing.items():
+            for e, d in details.items():
+                if abs(d['delta']) > max_delta:
+                    max_delta = abs(d['delta'])
+        return max_delta
+
+
+def oncosplice(mut_id, sai_threshold=0.5, protein_coding=True, primary_transcript=False, per_transcript_missplicing=False, window_length=13, save_spliceai_results=False, force_spliceai=False):
+    mutation = Variations(mut_id)
+    try:
+        reference_gene = Gene(mutation.gene)
+    except FileNotFoundError:
+        return pd.DataFrame()
+
+    reference_gene_proteines = {g.protein: g.transcript_id for g in reference_gene.run_transcripts()}
+    mutated_gene = Gene(mutation.gene, mut_id)
+
+
+    results = []
+    for variant in mutated_gene.run_transcripts(protein_coding=protein_coding, primary_transcript=primary_transcript):
+        reference = reference_gene.transcript(variant.transcript_id)
+        if mutation not in reference or reference.protein == '' or len(reference.protein) < window_length:
+            continue
+
+        cons_vector = transform_conservation_vector(reference.cons_vector, window=window_length)
+        # if per_transcript_missplicing:
+        missplicing_obj = PredictSpliceAI(mutation, reference, threshold=sai_threshold, force=force_spliceai, save_results=save_spliceai_results)
+        missplicing = missplicing_obj.apply_sai_threshold_primary(threshold=sai_threshold)
+        # print(missplicing)
+        for i, new_boundaries in enumerate(develop_aberrant_splicing(variant, missplicing)):
+            variant_isoform = deepcopy(variant)
+            variant_isoform.reset_acceptors(acceptors=new_boundaries['acceptors']).reset_donors(donors=new_boundaries['donors']).organize().generate_protein()
+            alignment = get_logical_alignment(reference.protein, variant_isoform.protein)
+            deleted, inserted = find_indels_with_mismatches_as_deletions(alignment.seqA, alignment.seqB)
+            modified_positions = find_modified_positions(len(reference.protein), deleted, inserted)
+            temp_cons = np.convolve(cons_vector * modified_positions, np.ones(window_length)) / window_length
+            affected_cons_scores = max(temp_cons)
+            percentile = (
+                        sorted(cons_vector).index(next(x for x in sorted(cons_vector) if x >= affected_cons_scores)) / len(
+                    cons_vector))
+
+            report = OncospliceAnnotator(reference, variant_isoform, mutation)
+            report['original_cons'] = reference.cons_vector
+            report['oncosplice_score'] = affected_cons_scores
+            report['percentile'] = percentile
+            report['modified_positions'] = modified_positions
+            report['cons_vector'] = cons_vector
+            report['isoform_id'] = i
+            report['isoform_prevalence'] = new_boundaries['path_weight']
+            report['full_missplicing'] = missplicing
+            report['missplicing'] = max(missplicing_obj)
+            report['reference_resemblance'] = reference_gene_proteines.get(variant_isoform.protein, None)
+            results.append(report)
+
+    report = pd.DataFrame(results)
+    return report
+
+

{geney-1.1.14.dist-info → geney-1.1.15.dist-info}/METADATA

@@ -1,6 +1,6 @@
 Metadata-Version: 2.1
 Name: geney
-Version: 1.1.14
+Version: 1.1.15
 Summary: A Python package for gene expression modeling.
 Home-page: https://github.com/nicolaslynn/geney
 Author: Nicolas Lynn
@@ -27,9 +27,12 @@ Requires-Dist: joblib ==1.3.2
 Requires-Dist: gtfparse ==1.3.0
 Requires-Dist: sh ==2.0.6
 Requires-Dist: termplotlib ==0.3.9
+Requires-Dist: torch
 Requires-Dist: lifelines
 Requires-Dist: notebook
 Requires-Dist: matplotlib
 Requires-Dist: dask[complete]
 Requires-Dist: dask-jobqueue
+Requires-Dist: gffutils
+Requires-Dist: pyfastx
 

{geney-1.1.14.dist-info → geney-1.1.15.dist-info}/RECORD

@@ -7,9 +7,10 @@ geney/config_setup.py,sha256=SePeooA4RWAtR_KAT1-W1hkD3MT5tH6YMyp80t_RNPQ,385
 geney/data_setup.py,sha256=DZeksRPr2ZT7bszMo33W0r3OwmqHokVXtZ4gx5Lu_Mo,10725
 geney/gtex.py,sha256=asL2lHyU5KsbWpV096vkf1Ka7hSo_RRfZqw7p5nERmE,1919
 geney/gtex_utils.py,sha256=asL2lHyU5KsbWpV096vkf1Ka7hSo_RRfZqw7p5nERmE,1919
-geney/immune_utils.py,sha256=elxjQyB52lYXrrt3sX6vtYlr_pTFEeCFzmEMP2qlPwA,5300
+geney/immune_utils.py,sha256=ZRni5ttrhpYBnmNr0d0ZatIbNPYs4nmQuoUO00SpsS4,5271
 geney/netchop.py,sha256=AMiy9YsdTmX4B3k3Y5Yh7EmoGAojM1O3AzhPKOiB--g,3050
-geney/oncosplice.py,sha256=hVSsQulgER5NZtmQB59LTLl5tOWPeWcpOpHquW_Z-DM,68965
+geney/oncosplice.py,sha256=vHKRq5Zkc0qhsMAe8sZKbGjjK6-Wgk_Si0EDHUU_BOY,68971
+geney/oncosplice_mouse.py,sha256=LYLOukI9qI1IBkyl1qVRFR5d1NAw7Orlj8Zth-4xCW8,12962
 geney/oncosplice_pipeline.py,sha256=hpGqFHOdn8i8tvvs1-t3-G9Ko18zInwoDXBJbbrfbC4,68036
 geney/performance_utils.py,sha256=FQt7rA4r-Wuq3kceCxsSuMfj3wU1tMG8QnbL59aBohs,4700
 geney/power_utils.py,sha256=6InuDm1jSrsgR-F_LmdMTbuQwty2OdYjwfGGaAPhaRI,7268
@@ -44,7 +45,7 @@ geney/translation_initiation/resources/kozak_pssm.json,sha256=pcd0Olziutq-6H3mFW
 geney/translation_initiation/resources/tis_regressor_model.joblib,sha256=IXb4DUDhJ5rBDKcqMk9zE3ECTZZcdj7Jixz3KpoZ7OA,2592025
 geney/translation_termination/__init__.py,sha256=47DEQpj8HBSa-_TImW-5JCeuQeRkm5NMpJWZG3hSuFU,0
 geney/translation_termination/tts_utils.py,sha256=47DEQpj8HBSa-_TImW-5JCeuQeRkm5NMpJWZG3hSuFU,0
-geney-1.1.14.dist-info/METADATA,sha256=zIhA9HkRpvesCUHmRo9Aml2qSmXBEYa6XBsISeWTtt0,1131
-geney-1.1.14.dist-info/WHEEL,sha256=iYlv5fX357PQyRT2o6tw1bN-YcKFFHKqB_LwHO5wP-g,110
-geney-1.1.14.dist-info/top_level.txt,sha256=O-FuNUMb5fn9dhZ-dYCgF0aZtfi1EslMstnzhc5IIVo,6
-geney-1.1.14.dist-info/RECORD,,
+geney-1.1.15.dist-info/METADATA,sha256=DMZ8ovJT_dpSe2rmM_m2LAc9nIZsOf4VUlLE__kscfY,1199
+geney-1.1.15.dist-info/WHEEL,sha256=iYlv5fX357PQyRT2o6tw1bN-YcKFFHKqB_LwHO5wP-g,110
+geney-1.1.15.dist-info/top_level.txt,sha256=O-FuNUMb5fn9dhZ-dYCgF0aZtfi1EslMstnzhc5IIVo,6
+geney-1.1.15.dist-info/RECORD,,