geney 1.4.16__py2.py3-none-any.whl → 1.4.18__py2.py3-none-any.whl

geney/Transcript.py

@@ -5,7 +5,7 @@ import copy
 from Bio.Seq import Seq  # Assuming Biopython is used
 from . import config
 from .utils.utils import unload_pickle
-from .utils.SeqMats import SeqMat #, MutSeqMat
+from .utils.SeqMatsOld import SeqMat #, MutSeqMat
 from .utils.Fasta_segment import Fasta_segment
 
 class Transcript:

geney/_oncosplice.py

@@ -4,7 +4,7 @@ from datetime import datetime
 from tqdm import tqdm
 import pandas as pd
 import numpy as np
-from geney.utils.SeqMats import MutSeqMat
+from geney.utils.SeqMatsOld import MutSeqMat
 from ._splicing_utils import find_transcript_missplicing_seqs, develop_aberrant_splicing, Missplicing
 from .Gene import Gene
 

geney/_splicing_utils.py

@@ -2,7 +2,7 @@ import numpy as np
 import pandas as pd
 
 from .Gene import Gene
-from geney.utils.SeqMats import MutSeqMat
+from geney.utils.SeqMatsOld import MutSeqMat
 from collections import defaultdict
 
 

geney/utils/SeqMats.py

@@ -1,11 +1,16 @@
+from __future__ import annotations
+
 __all__ = ['SeqMat', 'format_mut_id']
 
+
 from dataclasses import dataclass, field
+from typing import List, Tuple, Union, Optional
 from collections import defaultdict
-from typing import Optional, Union, List, Tuple
 import numpy as np
 import pandas as pd
 
+
+
 def format_mut_id(text):
     import re
     # text = "TP53:17:7579472:G:A"
@@ -25,417 +30,214 @@ def format_mut_id(text):
         return None
 
 
+
 @dataclass(slots=True)
 class SeqMat:
     """Represents a genomic sequence matrix used for training."""
-    # Metadata fields (uncomment and/or extend as needed)
-    name: str = field(default="Unnamed Sequence", metadata={"description": "Name of the sequence"})
-    version: str = field(default="1.0", metadata={"description": "Version of the dataset"})
-    source: str = field(default="Unknown", metadata={"description": "Source of the sequence data"})
-    notes: dict = field(default_factory=dict, metadata={"description": "User-defined metadata dictionary"})
+    name: str = field(default="Unnamed Sequence")
+    version: str = field(default="1.0")
+    source: str = field(default="Unknown")
+    notes: dict = field(default_factory=dict)
 
     seq_array: np.ndarray = field(init=False, repr=False)
     insertion_counters: dict = field(default_factory=lambda: defaultdict(int), init=False, repr=False)
     rev: bool = field(default=False, init=False, repr=False)
-
     predicted_splicing: pd.DataFrame = field(init=False, repr=False)
     _pos_to_idx: dict = field(default_factory=dict, init=False, repr=False)
 
     def __init__(
-            self,
-            nucleotides: str,
-            index: np.ndarray,
-            conservation: Optional[np.ndarray] = None,
-            reference_nucleotides: Optional[np.ndarray] = None,
-            notes: Optional[dict] = None,
-            source: Optional[str] = None,
-            rev: Optional[bool] = False,
-            name: Optional[str] = 'wild_type',
-            version: Optional[str] = 'none'
-
+        self,
+        nucleotides: str,
+        index: np.ndarray,
+        conservation: Optional[np.ndarray] = None,
+        reference_nucleotides: Optional[np.ndarray] = None,
+        notes: Optional[dict] = None,
+        source: Optional[str] = None,
+        rev: Optional[bool] = False,
+        name: Optional[str] = 'wild_type',
+        version: Optional[str] = 'none'
     ) -> None:
+        # Initialize metadata
+        self.name = name
+        self.version = version
+        self.source = source or "Unknown"
+        self.notes = notes or {}
+        self.rev = rev
         self.predicted_splicing = None
-        nucleotides = np.array(list(nucleotides))
-        L = nucleotides.shape[0]
+
+        # Build structured array
+        nts = np.array(list(nucleotides), dtype='S1')
+        L = len(nts)
         if index.shape[0] != L:
-            raise ValueError("Indices array length must match nucleotide sequence length.")
+            raise ValueError("Indices length must match sequence length.")
         if conservation is not None and conservation.shape[0] != L:
-            raise ValueError("Conservation vector length must match sequence length.")
-        if reference_nucleotides is not None and reference_nucleotides.shape[0] != L:
-            raise ValueError("Reference nucleotide vector length must match sequence length.")
+            raise ValueError("Conservation length must match sequence length.")
+        if reference_nucleotides is not None and len(reference_nucleotides) != L:
+            raise ValueError("Reference nucleotides length must match sequence length.")
 
         dtype = np.dtype([
-            ("nt", "S1"),
-            ("index", np.float64),
-            ("ref", "S1"),
-            ("cons", np.float32),
-            ("valid_mask", bool),
+            ('nt', 'S1'),
+            ('index', np.float64),
+            ('ref', 'S1'),
+            ('cons', np.float32),
+            ('valid_mask', bool)
         ])
-
         self.seq_array = np.empty(L, dtype=dtype)
-        self.seq_array["nt"] = nucleotides
-        # Use provided reference nucleotides if available.
-        self.seq_array["ref"] = nucleotides if reference_nucleotides is None else reference_nucleotides
-        self.seq_array["index"] = index
-        self.seq_array["cons"] = np.nan if conservation is None else conservation
-        self.seq_array["valid_mask"] = self.seq_array["nt"] != b"-"
+        self.seq_array['nt'] = nts
+        self.seq_array['ref'] = nts if reference_nucleotides is None else np.array(reference_nucleotides, dtype='S1')
+        self.seq_array['index'] = index
+        self.seq_array['cons'] = (np.zeros(L, dtype='f4') if conservation is None else conservation)
+        self.seq_array['valid_mask'] = self.seq_array['nt'] != b'-'
+
+        # Initialize helpers
         self.insertion_counters = defaultdict(int)
-        self._pos_to_idx = {pos: i for i, pos in enumerate(self.seq_array["index"])}
+        self._build_index_map()
 
-        self.source = source if source is not None else "Unknown"
-        self.notes = notes if notes is not None else {}
-        self.name = name
-        self.rev = rev
-        self.version = version
+    def _build_index_map(self):
+        """Rebuild position-to-index lookup."""
+        self._pos_to_idx = {float(pos): i for i, pos in enumerate(self.seq_array['index'])}
 
     def __len__(self) -> int:
-        return int(self.seq_array["valid_mask"].sum())
-
-    def __repr__(self):
-        return f"<SeqMat: {self.seq}>"
-
-    def __str__(self):
-        return self.seq
-
-    def get_metadata(self) -> dict:
-        """Retrieve all metadata as a dictionary."""
-        return {
-            "name": self.name,
-            "source": self.source,
-            "version": self.version,
-            "notes": self.notes
-        }
+        return int(self.seq_array['valid_mask'].sum())
 
     @property
     def seq(self) -> str:
-        return self.seq_array["nt"][self.seq_array["valid_mask"]].tobytes().decode()
+        return self.seq_array['nt'][self.seq_array['valid_mask']].tobytes().decode()
 
     @property
     def index(self) -> np.ndarray:
-        return self.seq_array["index"][self.seq_array["valid_mask"]]
+        return self.seq_array['index'][self.seq_array['valid_mask']]
 
     @property
     def conservation(self) -> np.ndarray:
-        return self.seq_array["cons"][self.seq_array["valid_mask"]]
-
-    @property
-    def max_index(self) -> float:
-        return self.seq_array["index"].max()
-
-    @property
-    def min_index(self) -> float:
-        return self.seq_array["index"].min()
-
-    @property
-    def start(self) -> float:
-        return self.min_index
-
-    @property
-    def end(self) -> float:
-        return self.max_index
-
-    @property
-    def mutated_positions(self) -> np.ndarray:
-        return (self.seq_array["ref"] != self.seq_array["nt"])[self.seq_array["valid_mask"]].astype(int)
-
-    def clone(self, start: Optional[int] = None, end: Optional[int] = None) -> "SeqMat":
-        cloned = SeqMat.__new__(SeqMat)
+        return self.seq_array['cons'][self.seq_array['valid_mask']]
+
+    def clone(self, start: Optional[float] = None, end: Optional[float] = None) -> SeqMat:
+        new = SeqMat.__new__(SeqMat)
+        # copy metadata
+        new.name = self.name
+        new.version = self.version
+        new.source = self.source
+        new.notes = self.notes.copy()
+        new.rev = self.rev
+        new.predicted_splicing = None
+        new.insertion_counters = defaultdict(int)
+
+        # slice or full copy
         if start is not None and end is not None:
-            cloned.seq_array = self.seq_array[(self.seq_array["index"] >= start) & (self.seq_array["index"] <= end)]
+            mask = (self.seq_array['index'] >= start) & (self.seq_array['index'] <= end)
+            new.seq_array = self.seq_array[mask].copy()
         else:
-            cloned.seq_array = self.seq_array.copy()
-        cloned.insertion_counters = defaultdict(int)
-        cloned.name = self.name
-        cloned.source = self.source
-        cloned.version = self.version
-        cloned.notes = self.notes.copy()
-        cloned.rev = self.rev
-
-        cloned._pos_to_idx = {pos: i for i, pos in enumerate(cloned.seq_array["index"])}
-
-        return cloned
-
-    def apply_mutation(self, pos: int, ref: str, alt: str, only_snps: bool = False):
-        """
-        Applies a mutation (SNP, substitution, insertion, or deletion) to the sequence.
-
-        Parameters:
-            pos (int): The reference position where the mutation should occur.
-            ref (str): The reference allele (use '-' for insertions).
-            alt (str): The alternate allele (use '-' for deletions).
-            only_snps (bool): If True, only SNP substitutions are allowed; indels are ignored.
-
-        Returns:
-            SeqMat: The mutated sequence matrix.
-
-        The method normalizes the mutation (dropping any shared prefix) and then applies:
-         - A SNP/substitution if both alleles are non-gap.
-         - An insertion if ref is '-' (after normalization).
-         - A deletion if alt is '-' (after normalization).
-
-        For insertions, new rows are added with fractional indices computed from an insertion counter.
-        For deletions, the corresponding rows are removed.
-        """
-        return_to_rc = False
+            new.seq_array = self.seq_array.copy()
+
+        new._build_index_map()
+        return new
+
+    def apply_mutation(self, pos: float, ref: str, alt: str, only_snps: bool = False) -> SeqMat:
+        """Apply a single mutation to this SeqMat."""
+        # reverse-complement context
         if self.rev:
-            return_to_rc = True
             self.reverse_complement()
 
-        # Normalize shared prefix (similar to left-alignment in VCFs)
+        # left-normalize
         while ref and alt and ref[0] == alt[0]:
             pos += 1
-            ref = ref[1:] or "-"
-            alt = alt[1:] or "-"
+            ref = ref[1:] or '-'
+            alt = alt[1:] or '-'
 
-        # Case 1: SNP or multi-base substitution
-        if ref != "-" and alt != "-":
+        # substitution
+        if ref != '-' and alt != '-':
             if len(ref) != len(alt):
-                raise ValueError("Substitution mutations must have alleles of equal length.")
-
-            pos_idx = np.searchsorted(self.seq_array["index"], pos)
-            # pos_idx = self._pos_to_idx.get(pos)
-
-            if pos_idx is None:
-                raise ValueError(f"Position {pos} not found in index")
-
-            end_idx = pos_idx + len(ref)
-            if end_idx > len(self.seq_array):
-                raise ValueError(f"Substitution range exceeds sequence length at position {pos}.")
-
-            # segment = self.seq_array["ref"][pos_idx:end_idx].tobytes().decode()
-            # if segment != ref:
-            #     raise ValueError(f"Reference mismatch at position {pos}: expected '{ref}', found '{segment}'")
-
-            ref_segment = self.seq_array["ref"][pos_idx:end_idx]
-            # expected_segment = np.frombuffer(ref.encode(), dtype='S1')
-            if not np.all(ref_segment == np.frombuffer(ref.encode(), dtype='S1')):
-                actual_str = ref_segment.tobytes().decode()
-                raise ValueError(f"Reference mismatch at position {pos}: expected '{ref}', found '{actual_str}'")
-            self.seq_array["nt"][pos_idx:end_idx] = np.frombuffer(alt.encode(), dtype='S1')
-
-            # for i, nt in enumerate(alt):
-            #     self.seq_array["nt"][pos_idx + i] = nt.encode()
-
-        # Case 2: Insertion (ref is '-' means nothing was present, and we need to add bases)
-        elif ref == "-" and alt != "-":
+                raise ValueError("Substitution requires equal-length alleles.")
+            idx = self._pos_to_idx.get(pos)
+            if idx is None:
+                raise KeyError(f"Position {pos} not found.")
+            end = idx + len(ref)
+            if end > len(self.seq_array):
+                raise IndexError(f"Out of bounds at {pos}.")
+            # verify reference
+            ref_seg = self.seq_array['ref'][idx:end]
+            if not np.array_equal(ref_seg, np.frombuffer(ref.encode(), dtype='S1')):
+                raise ValueError(f"Ref mismatch at {pos}.")
+            # assign alt
+            self.seq_array['nt'][idx:end] = np.frombuffer(alt.encode(), dtype='S1')
+
+        # insertion
+        elif ref == '-' and alt != '-':
             if only_snps:
-                return self  # Skip if indels are not allowed.
-            pos_idx = np.searchsorted(self.seq_array["index"], pos)
-            insertion_count = self.insertion_counters[pos]
+                return self
+            idx = self._pos_to_idx.get(pos)
+            if idx is None:
+                raise KeyError(f"Position {pos} not found.")
+            cnt = self.insertion_counters[pos]
             eps = 1e-6
             new_rows = []
             for i, nt in enumerate(alt):
-                new_index = pos + (insertion_count + i + 1) * eps
-                new_row = (nt.encode(), new_index, b"-", np.float32(np.nan), True)
-                new_rows.append(new_row)
-            rows = list(self.seq_array)
-            rows.extend(new_rows)
-            new_seq_array = np.array(rows, dtype=self.seq_array.dtype)
-            new_seq_array.sort(order="index")
-            self.seq_array = new_seq_array
+                new_rows.append((nt.encode(),
+                                 pos + (cnt + i + 1)*eps,
+                                 b'-',
+                                 np.nan,
+                                 True))
+            self._insert_rows(idx, new_rows)
             self.insertion_counters[pos] += len(alt)
 
-        # Case 3: Deletion (alt is '-' means bases are to be removed)
-        elif alt == "-" and ref != "-":
+        # deletion
+        elif alt == '-' and ref != '-':
             if only_snps:
-                return self  # Skip if indels are not allowed.
-            pos_idx = np.searchsorted(self.seq_array["index"], pos)
-            end_idx = pos_idx + len(ref)
-            if end_idx > len(self.seq_array):
-                raise ValueError(f"Deletion range exceeds sequence length at position {pos}.")
-            segment = self.seq_array["ref"][pos_idx:end_idx].tobytes().decode()
-            if segment != ref:
-                raise ValueError(
-                    f"Reference mismatch for deletion at position {pos}: expected '{ref}', found '{segment}'")
-            self.seq_array = np.delete(self.seq_array, np.s_[pos_idx:end_idx])
+                return self
+            idx = self._pos_to_idx.get(pos)
+            if idx is None:
+                raise KeyError(f"Position {pos} not found.")
+            end = idx + len(ref)
+            # verify
+            ref_seg = self.seq_array['ref'][idx:end]
+            if not np.array_equal(ref_seg, np.frombuffer(ref.encode(), dtype='S1')):
+                raise ValueError(f"Ref mismatch at {pos}.")
+            self.seq_array = np.delete(self.seq_array, np.s_[idx:end])
+
         else:
-            raise ValueError("Unsupported mutation type. Provide valid ref and alt values.")
+            raise ValueError("Unsupported mutation type.")
 
-        self.seq_array["valid_mask"] = self.seq_array["nt"] != b"-"
-        if return_to_rc:
-            self.reverse_complement()
+        # update mask & index map
+        self.seq_array['valid_mask'] = self.seq_array['nt'] != b'-'
+        self._build_index_map()
 
+        # restore orientation
+        if self.rev:
+            self.reverse_complement()
         return self
 
+    def _insert_rows(self, idx: int, rows: List[tuple]):
+        """Helper to insert new rows efficiently and resort."""
+        arr = self.seq_array.tolist()
+        arr[idx:idx] = rows
+        new = np.array(arr, dtype=self.seq_array.dtype)
+        new.sort(order='index')
+        self.seq_array = new
+
+    def complement(self) -> SeqMat:
+        comp = {b'A':b'T', b'T':b'A', b'C':b'G', b'G':b'C', b'-':b'-'}
+        nts = np.array([comp[x] for x in self.seq_array['nt']], dtype='S1')
+        new = self.clone()
+        new.seq_array['nt'] = nts
+        return new
+
+    def reverse_complement(self) -> SeqMat:
+        new = self.complement().clone()
+        new.seq_array = new.seq_array[::-1].copy()
+        new.rev = not self.rev
+        return new
+
     def __getitem__(self, key: Union[int, slice]) -> np.ndarray:
+        idx = None
         if isinstance(key, int):
-            pos_idx = np.where(self.seq_array["index"] == key)[0]
-            if pos_idx.size == 0:
-                raise IndexError(f"Position {key} not found in sequence.")
-            return self.seq_array[pos_idx[0]]
-        elif isinstance(key, slice):
-            start, stop = key.start, key.stop
-            if start is None:
-                start = self.seq_array["index"].min()
-            if stop is None:
-                stop = self.seq_array["index"].max()
-            return self.seq_array[(self.seq_array["index"] >= start) & (self.seq_array["index"] <= stop)]
-        else:
-            raise TypeError("Indexing must be an integer or a slice.")
-
-    def complement(self) -> "SeqMat":
-        comp_dict = {b"A": b"T", b"T": b"A", b"C": b"G", b"G": b"C", b"-": b"-", b"N": b"N"}
-        comp_seq = np.array([comp_dict[nt] for nt in self.seq_array["nt"]], dtype="S1")
-        new_instance = self.clone()
-        new_instance.seq_array["nt"] = comp_seq
-        return new_instance
-
-    def reverse_complement(self) -> "SeqMat":
-        rev_comp_seq = self.complement().seq_array[::-1]
-        self.seq_array = rev_comp_seq.copy()
-        self.rev = not self.rev
-        return self
-
-    # def splice_out(self, introns: List[Tuple[int, int]]) -> "SeqMat":
-    #     """
-    #     Splices out regions from the sequence corresponding to the given intron boundaries.
-    #
-    #     Args:
-    #         introns (List[Tuple[int, int]]): List of (start, end) intron boundaries to remove.
-    #                                          Coordinates should match the 'index' field.
-    #
-    #     Returns:
-    #         SeqMat: A new instance with the intron regions removed.
-    #     """
-    #     mask = np.ones(len(self.seq_array), dtype=bool)
-    #
-    #     for start, end in introns:
-    #         mask &= ~((self.seq_array["index"] >= start) & (self.seq_array["index"] <= end))
-    #
-    #     new_instance = self.clone()
-    #     new_instance.seq_array = self.seq_array[mask].copy()
-    #     return new_instance
-
-    def cut_out(self, introns: List[Tuple[int, int]]) -> "SeqMat":
-        """
-        Splices out regions from the sequence corresponding to the given intron boundaries.
-
-        Handles reverse-complemented sequences by interpreting introns in reverse as well.
-
-        Args:
-            introns (List[Tuple[int, int]]): List of (start, end) intron boundaries.
-                                             These are always genomic (absolute) coordinates,
-                                             regardless of strand direction.
-
-        Returns:
-            SeqMat: A new instance with the intron regions removed.
-        """
-        # In reverse orientation, flip intron direction for comparison
-        if self.rev:
-            introns = [(end, start) if start > end else (start, end) for (start, end) in introns]
-
-        mask = np.ones(len(self.seq_array), dtype=bool)
-
-        for start, end in introns:
-            lo, hi = min(start, end) + 1, max(start, end) - 1
-            mask &= ~((self.seq_array["index"] >= lo) & (self.seq_array["index"] <= hi))
-
-        new_instance = self.clone()
-        new_instance.seq_array = self.seq_array[mask].copy()
-        return new_instance
-
-    def open_reading_frame(self, tis: int) -> "SeqMat":
-        """
-        Extracts the open reading frame starting from the translation initiation site (TIS)
-        until the first in-frame stop codon.
-
-        Args:
-            tis (int): Genomic position of the translation initiation site (start codon).
-
-        Returns:
-            SeqMat: A new SeqMat instance containing the ORF (from TIS to stop codon inclusive).
-        """
-        if tis not in self.seq_array["index"]:
-            print(f"Warning: TIS position {tis} not found, returning default.")
-            return self.clone(start=0, end=3)
-
-        # Extract nucleotide sequence and indices starting from TIS
-        mask = self.seq_array["index"] >= tis if not self.rev else self.seq_array["index"] <= tis
-        coding_part = self.seq_array[mask]
-        coding_seq = coding_part["nt"].tobytes().decode()
-
-        # Read codons in-frame
-        for i in range(0, len(coding_seq) - 2, 3):
-            codon = coding_seq[i:i + 3]
-            if codon in {"TAA", "TAG", "TGA"}:
-                # Determine index range for this ORF
-                start = coding_part["index"][0]
-                stop = coding_part["index"][i + 2]
-                lo, hi = sorted((start, stop))
-                return self.clone(start=lo, end=hi)
-
-        raise ValueError("No in-frame stop codon found after the TIS.")
-
-    def predict_splicing(self, position: int, engine='spliceai', context=7500, inplace=False): #, reference_donors=None, reference_acceptors=None) -> pd.DataFrame:
-        """
-        Predict splicing probabilities at a given position using the specified engine.
-
-        Args:
-            position (int): The genomic position to predict splicing probabilities for.
-            engine (str): The prediction engine to use. Supported: 'spliceai', 'pangolin'.
-            context (int): The length of the target central region (default: 7500).
-            format (str): Output format for the splicing engine results.
-
-        Returns:
-            pd.DataFrame: A DataFrame containing:
-                - position: The genomic position
-                - donor_prob: Probability of being a donor splice site
-                - acceptor_prob: Probability of being an acceptor splice site
-                - nucleotides: The nucleotide sequence at that position
-
-        Raises:
-            ValueError: If an unsupported engine is provided.
-            IndexError: If the position is not found in the sequence.
-        """
-        # Retrieve extended context (includes flanks) around the position.
-        # seq, indices = self.get_context(position, context=context, padding='N')
-        target = self.clone(position - context, position + context)
-        # print(len(target.seq))
-        seq, indices = target.seq, target.index
-        # print(len(seq))
-        # rel_pos = np.where(indices == position)[0][0]
-        # print(rel_pos)
-        rel_pos = np.abs(indices - position).argmin()
-        # print(rel_pos, len(seq))
-        left_missing, right_missing = max(0, context - rel_pos), max(0, context - (len(seq) - rel_pos))
-        # print(left_missing, right_missing)
-        if left_missing > 0 or right_missing > 0:
-            step = -1 if self.rev else 1
-
-            if left_missing > 0:
-                left_pad = np.arange(indices[0] - step * left_missing, indices[0], step)
-            else:
-                left_pad = np.array([], dtype=indices.dtype)
-
-            if right_missing > 0:
-                right_pad = np.arange(indices[-1] + step, indices[-1] + step * (right_missing + 1), step)
-            else:
-                right_pad = np.array([], dtype=indices.dtype)
-
-            seq = 'N' * left_missing + seq + 'N' * right_missing
-            indices = np.concatenate([left_pad, indices, right_pad])
-
-        # Run the splicing prediction engine (function assumed to be defined externally)
-        from .splicing_utils import run_splicing_engine
-        donor_probs, acceptor_probs = run_splicing_engine(seq, engine)
-        # Trim off the fixed flanks before returning results.
-        seq = seq[5000:-5000]
-        indices = indices[5000:-5000]
-        df = pd.DataFrame({
-            'position': indices,
-            'donor_prob': donor_probs,
-            'acceptor_prob': acceptor_probs,
-            'nucleotides': list(seq)
-        }).set_index('position').round(3)
-        # if reference_donors is not None:
-        #     df['ref_donor'] = df.index.isin(reference_donors).astype(int)
-        # if reference_acceptors is not None:
-        #     df['ref_acceptor'] = df.index.isin(reference_acceptors).astype(int)
-
-        df.attrs['name'] = self.name
-        if inplace:
-            self.predicted_splicing = df
-            return self
-        else:
-            return df
-
+            idx = self._pos_to_idx.get(float(key))
+            if idx is None:
+                raise KeyError(f"Position {key} not found.")
+            return self.seq_array[idx]
+        if isinstance(key, slice):
+            start = key.start or self.min_index
+            stop = key.stop or self.max_index
+            mask = (self.seq_array['index'] >= start) & (self.seq_array['index'] <= stop)
+            return self.seq_array[mask]
+        raise TypeError("Invalid index type.")

geney/utils/SeqMatsOld.py

@@ -0,0 +1,441 @@
+__all__ = ['SeqMat', 'format_mut_id']
+
+from dataclasses import dataclass, field
+from collections import defaultdict
+from typing import Optional, Union, List, Tuple
+import numpy as np
+import pandas as pd
+
+def format_mut_id(text):
+    import re
+    # text = "TP53:17:7579472:G:A"
+
+    pattern = r'^[^:]+:[^:]+:(\d+):([ACGTN\-]+):([ACGTN\-]+)$'
+    match = re.match(pattern, text)
+
+    if match:
+        position = int(match.group(1))
+        ref = match.group(2)
+        alt = match.group(3)
+        return {'pos': position, 'ref': ref, 'alt': alt}
+
+        # print(f"Position: {position}, Ref: {ref}, Alt: {alt}")
+    else:
+        print("No match")
+        return None
+
+
+@dataclass(slots=True)
+class SeqMat:
+    """Represents a genomic sequence matrix used for training."""
+    # Metadata fields (uncomment and/or extend as needed)
+    name: str = field(default="Unnamed Sequence", metadata={"description": "Name of the sequence"})
+    version: str = field(default="1.0", metadata={"description": "Version of the dataset"})
+    source: str = field(default="Unknown", metadata={"description": "Source of the sequence data"})
+    notes: dict = field(default_factory=dict, metadata={"description": "User-defined metadata dictionary"})
+
+    seq_array: np.ndarray = field(init=False, repr=False)
+    insertion_counters: dict = field(default_factory=lambda: defaultdict(int), init=False, repr=False)
+    rev: bool = field(default=False, init=False, repr=False)
+
+    predicted_splicing: pd.DataFrame = field(init=False, repr=False)
+    _pos_to_idx: dict = field(default_factory=dict, init=False, repr=False)
+
+    def __init__(
+            self,
+            nucleotides: str,
+            index: np.ndarray,
+            conservation: Optional[np.ndarray] = None,
+            reference_nucleotides: Optional[np.ndarray] = None,
+            notes: Optional[dict] = None,
+            source: Optional[str] = None,
+            rev: Optional[bool] = False,
+            name: Optional[str] = 'wild_type',
+            version: Optional[str] = 'none'
+
+    ) -> None:
+        self.predicted_splicing = None
+        nucleotides = np.array(list(nucleotides))
+        L = nucleotides.shape[0]
+        if index.shape[0] != L:
+            raise ValueError("Indices array length must match nucleotide sequence length.")
+        if conservation is not None and conservation.shape[0] != L:
+            raise ValueError("Conservation vector length must match sequence length.")
+        if reference_nucleotides is not None and reference_nucleotides.shape[0] != L:
+            raise ValueError("Reference nucleotide vector length must match sequence length.")
+
+        dtype = np.dtype([
+            ("nt", "S1"),
+            ("index", np.float64),
+            ("ref", "S1"),
+            ("cons", np.float32),
+            ("valid_mask", bool),
+        ])
+
+        self.seq_array = np.empty(L, dtype=dtype)
+        self.seq_array["nt"] = nucleotides
+        # Use provided reference nucleotides if available.
+        self.seq_array["ref"] = nucleotides if reference_nucleotides is None else reference_nucleotides
+        self.seq_array["index"] = index
+        self.seq_array["cons"] = np.nan if conservation is None else conservation
+        self.seq_array["valid_mask"] = self.seq_array["nt"] != b"-"
+        self.insertion_counters = defaultdict(int)
+        self._pos_to_idx = {pos: i for i, pos in enumerate(self.seq_array["index"])}
+
+        self.source = source if source is not None else "Unknown"
+        self.notes = notes if notes is not None else {}
+        self.name = name
+        self.rev = rev
+        self.version = version
+
+    def __len__(self) -> int:
+        return int(self.seq_array["valid_mask"].sum())
+
+    def __repr__(self):
+        return f"<SeqMat: {self.seq}>"
+
+    def __str__(self):
+        return self.seq
+
+    def get_metadata(self) -> dict:
+        """Retrieve all metadata as a dictionary."""
+        return {
+            "name": self.name,
+            "source": self.source,
+            "version": self.version,
+            "notes": self.notes
+        }
+
+    @property
+    def seq(self) -> str:
+        return self.seq_array["nt"][self.seq_array["valid_mask"]].tobytes().decode()
+
+    @property
+    def index(self) -> np.ndarray:
+        return self.seq_array["index"][self.seq_array["valid_mask"]]
+
+    @property
+    def conservation(self) -> np.ndarray:
+        return self.seq_array["cons"][self.seq_array["valid_mask"]]
+
+    @property
+    def max_index(self) -> float:
+        return self.seq_array["index"].max()
+
+    @property
+    def min_index(self) -> float:
+        return self.seq_array["index"].min()
+
+    @property
+    def start(self) -> float:
+        return self.min_index
+
+    @property
+    def end(self) -> float:
+        return self.max_index
+
+    @property
+    def mutated_positions(self) -> np.ndarray:
+        return (self.seq_array["ref"] != self.seq_array["nt"])[self.seq_array["valid_mask"]].astype(int)
+
+    def clone(self, start: Optional[int] = None, end: Optional[int] = None) -> "SeqMat":
+        cloned = SeqMat.__new__(SeqMat)
+        if start is not None and end is not None:
+            cloned.seq_array = self.seq_array[(self.seq_array["index"] >= start) & (self.seq_array["index"] <= end)]
+        else:
+            cloned.seq_array = self.seq_array.copy()
+        cloned.insertion_counters = defaultdict(int)
+        cloned.name = self.name
+        cloned.source = self.source
+        cloned.version = self.version
+        cloned.notes = self.notes.copy()
+        cloned.rev = self.rev
+
+        cloned._pos_to_idx = {pos: i for i, pos in enumerate(cloned.seq_array["index"])}
+
+        return cloned
+
+    def apply_mutation(self, pos: int, ref: str, alt: str, only_snps: bool = False):
+        """
+        Applies a mutation (SNP, substitution, insertion, or deletion) to the sequence.
+
+        Parameters:
+            pos (int): The reference position where the mutation should occur.
+            ref (str): The reference allele (use '-' for insertions).
+            alt (str): The alternate allele (use '-' for deletions).
+            only_snps (bool): If True, only SNP substitutions are allowed; indels are ignored.
+
+        Returns:
+            SeqMat: The mutated sequence matrix.
+
+        The method normalizes the mutation (dropping any shared prefix) and then applies:
+         - A SNP/substitution if both alleles are non-gap.
+         - An insertion if ref is '-' (after normalization).
+         - A deletion if alt is '-' (after normalization).
+
+        For insertions, new rows are added with fractional indices computed from an insertion counter.
+        For deletions, the corresponding rows are removed.
+        """
+        return_to_rc = False
+        if self.rev:
+            return_to_rc = True
+            self.reverse_complement()
+
+        # Normalize shared prefix (similar to left-alignment in VCFs)
+        while ref and alt and ref[0] == alt[0]:
+            pos += 1
+            ref = ref[1:] or "-"
+            alt = alt[1:] or "-"
+
+        # Case 1: SNP or multi-base substitution
+        if ref != "-" and alt != "-":
+            if len(ref) != len(alt):
+                raise ValueError("Substitution mutations must have alleles of equal length.")
+
+            pos_idx = np.searchsorted(self.seq_array["index"], pos)
+            # pos_idx = self._pos_to_idx.get(pos)
+
+            if pos_idx is None:
+                raise ValueError(f"Position {pos} not found in index")
+
+            end_idx = pos_idx + len(ref)
+            if end_idx > len(self.seq_array):
+                raise ValueError(f"Substitution range exceeds sequence length at position {pos}.")
+
+            # segment = self.seq_array["ref"][pos_idx:end_idx].tobytes().decode()
+            # if segment != ref:
+            #     raise ValueError(f"Reference mismatch at position {pos}: expected '{ref}', found '{segment}'")
+
+            ref_segment = self.seq_array["ref"][pos_idx:end_idx]
+            # expected_segment = np.frombuffer(ref.encode(), dtype='S1')
+            if not np.all(ref_segment == np.frombuffer(ref.encode(), dtype='S1')):
+                actual_str = ref_segment.tobytes().decode()
+                raise ValueError(f"Reference mismatch at position {pos}: expected '{ref}', found '{actual_str}'")
+            self.seq_array["nt"][pos_idx:end_idx] = np.frombuffer(alt.encode(), dtype='S1')
+
+            # for i, nt in enumerate(alt):
+            #     self.seq_array["nt"][pos_idx + i] = nt.encode()
+
+        # Case 2: Insertion (ref is '-' means nothing was present, and we need to add bases)
+        elif ref == "-" and alt != "-":
+            if only_snps:
+                return self  # Skip if indels are not allowed.
+            pos_idx = np.searchsorted(self.seq_array["index"], pos)
+            insertion_count = self.insertion_counters[pos]
+            eps = 1e-6
+            new_rows = []
+            for i, nt in enumerate(alt):
+                new_index = pos + (insertion_count + i + 1) * eps
+                new_row = (nt.encode(), new_index, b"-", np.float32(np.nan), True)
+                new_rows.append(new_row)
+            rows = list(self.seq_array)
+            rows.extend(new_rows)
+            new_seq_array = np.array(rows, dtype=self.seq_array.dtype)
+            new_seq_array.sort(order="index")
+            self.seq_array = new_seq_array
+            self.insertion_counters[pos] += len(alt)
+
+        # Case 3: Deletion (alt is '-' means bases are to be removed)
+        elif alt == "-" and ref != "-":
+            if only_snps:
+                return self  # Skip if indels are not allowed.
+            pos_idx = np.searchsorted(self.seq_array["index"], pos)
+            end_idx = pos_idx + len(ref)
+            if end_idx > len(self.seq_array):
+                raise ValueError(f"Deletion range exceeds sequence length at position {pos}.")
+            segment = self.seq_array["ref"][pos_idx:end_idx].tobytes().decode()
+            if segment != ref:
+                raise ValueError(
+                    f"Reference mismatch for deletion at position {pos}: expected '{ref}', found '{segment}'")
+            self.seq_array = np.delete(self.seq_array, np.s_[pos_idx:end_idx])
+        else:
+            raise ValueError("Unsupported mutation type. Provide valid ref and alt values.")
+
+        self.seq_array["valid_mask"] = self.seq_array["nt"] != b"-"
+        if return_to_rc:
+            self.reverse_complement()
+
+        return self
+
+    def __getitem__(self, key: Union[int, slice]) -> np.ndarray:
+        if isinstance(key, int):
+            pos_idx = np.where(self.seq_array["index"] == key)[0]
+            if pos_idx.size == 0:
+                raise IndexError(f"Position {key} not found in sequence.")
+            return self.seq_array[pos_idx[0]]
+        elif isinstance(key, slice):
+            start, stop = key.start, key.stop
+            if start is None:
+                start = self.seq_array["index"].min()
+            if stop is None:
+                stop = self.seq_array["index"].max()
+            return self.seq_array[(self.seq_array["index"] >= start) & (self.seq_array["index"] <= stop)]
+        else:
+            raise TypeError("Indexing must be an integer or a slice.")
+
+    def complement(self) -> "SeqMat":
+        comp_dict = {b"A": b"T", b"T": b"A", b"C": b"G", b"G": b"C", b"-": b"-", b"N": b"N"}
+        comp_seq = np.array([comp_dict[nt] for nt in self.seq_array["nt"]], dtype="S1")
+        new_instance = self.clone()
+        new_instance.seq_array["nt"] = comp_seq
+        return new_instance
+
+    def reverse_complement(self) -> "SeqMat":
+        rev_comp_seq = self.complement().seq_array[::-1]
+        self.seq_array = rev_comp_seq.copy()
+        self.rev = not self.rev
+        return self
+
+    # def splice_out(self, introns: List[Tuple[int, int]]) -> "SeqMat":
+    #     """
+    #     Splices out regions from the sequence corresponding to the given intron boundaries.
+    #
+    #     Args:
+    #         introns (List[Tuple[int, int]]): List of (start, end) intron boundaries to remove.
+    #                                          Coordinates should match the 'index' field.
+    #
+    #     Returns:
+    #         SeqMat: A new instance with the intron regions removed.
+    #     """
+    #     mask = np.ones(len(self.seq_array), dtype=bool)
+    #
+    #     for start, end in introns:
+    #         mask &= ~((self.seq_array["index"] >= start) & (self.seq_array["index"] <= end))
+    #
+    #     new_instance = self.clone()
+    #     new_instance.seq_array = self.seq_array[mask].copy()
+    #     return new_instance
+
+    def cut_out(self, introns: List[Tuple[int, int]]) -> "SeqMat":
+        """
+        Splices out regions from the sequence corresponding to the given intron boundaries.
+
+        Handles reverse-complemented sequences by interpreting introns in reverse as well.
+
+        Args:
+            introns (List[Tuple[int, int]]): List of (start, end) intron boundaries.
+                                             These are always genomic (absolute) coordinates,
+                                             regardless of strand direction.
+
+        Returns:
+            SeqMat: A new instance with the intron regions removed.
+        """
+        # In reverse orientation, flip intron direction for comparison
+        if self.rev:
+            introns = [(end, start) if start > end else (start, end) for (start, end) in introns]
+
+        mask = np.ones(len(self.seq_array), dtype=bool)
+
+        for start, end in introns:
+            lo, hi = min(start, end) + 1, max(start, end) - 1
+            mask &= ~((self.seq_array["index"] >= lo) & (self.seq_array["index"] <= hi))
+
+        new_instance = self.clone()
+        new_instance.seq_array = self.seq_array[mask].copy()
+        return new_instance
+
+    def open_reading_frame(self, tis: int) -> "SeqMat":
+        """
+        Extracts the open reading frame starting from the translation initiation site (TIS)
+        until the first in-frame stop codon.
+
+        Args:
+            tis (int): Genomic position of the translation initiation site (start codon).
+
+        Returns:
+            SeqMat: A new SeqMat instance containing the ORF (from TIS to stop codon inclusive).
+        """
+        if tis not in self.seq_array["index"]:
+            print(f"Warning: TIS position {tis} not found, returning default.")
+            return self.clone(start=0, end=3)
+
+        # Extract nucleotide sequence and indices starting from TIS
+        mask = self.seq_array["index"] >= tis if not self.rev else self.seq_array["index"] <= tis
+        coding_part = self.seq_array[mask]
+        coding_seq = coding_part["nt"].tobytes().decode()
+
+        # Read codons in-frame
+        for i in range(0, len(coding_seq) - 2, 3):
+            codon = coding_seq[i:i + 3]
+            if codon in {"TAA", "TAG", "TGA"}:
+                # Determine index range for this ORF
+                start = coding_part["index"][0]
+                stop = coding_part["index"][i + 2]
+                lo, hi = sorted((start, stop))
+                return self.clone(start=lo, end=hi)
+
+        raise ValueError("No in-frame stop codon found after the TIS.")
+
+    def predict_splicing(self, position: int, engine='spliceai', context=7500, inplace=False): #, reference_donors=None, reference_acceptors=None) -> pd.DataFrame:
+        """
+        Predict splicing probabilities at a given position using the specified engine.
+
+        Args:
+            position (int): The genomic position to predict splicing probabilities for.
+            engine (str): The prediction engine to use. Supported: 'spliceai', 'pangolin'.
+            context (int): The length of the target central region (default: 7500).
+            format (str): Output format for the splicing engine results.
+
+        Returns:
+            pd.DataFrame: A DataFrame containing:
+                - position: The genomic position
+                - donor_prob: Probability of being a donor splice site
+                - acceptor_prob: Probability of being an acceptor splice site
+                - nucleotides: The nucleotide sequence at that position
+
+        Raises:
+            ValueError: If an unsupported engine is provided.
+            IndexError: If the position is not found in the sequence.
+        """
+        # Retrieve extended context (includes flanks) around the position.
+        # seq, indices = self.get_context(position, context=context, padding='N')
+        target = self.clone(position - context, position + context)
+        # print(len(target.seq))
+        seq, indices = target.seq, target.index
+        # print(len(seq))
+        # rel_pos = np.where(indices == position)[0][0]
+        # print(rel_pos)
+        rel_pos = np.abs(indices - position).argmin()
+        # print(rel_pos, len(seq))
+        left_missing, right_missing = max(0, context - rel_pos), max(0, context - (len(seq) - rel_pos))
+        # print(left_missing, right_missing)
+        if left_missing > 0 or right_missing > 0:
+            step = -1 if self.rev else 1
+
+            if left_missing > 0:
+                left_pad = np.arange(indices[0] - step * left_missing, indices[0], step)
+            else:
+                left_pad = np.array([], dtype=indices.dtype)
+
+            if right_missing > 0:
+                right_pad = np.arange(indices[-1] + step, indices[-1] + step * (right_missing + 1), step)
+            else:
+                right_pad = np.array([], dtype=indices.dtype)
+
+            seq = 'N' * left_missing + seq + 'N' * right_missing
+            indices = np.concatenate([left_pad, indices, right_pad])
+
+        # Run the splicing prediction engine (function assumed to be defined externally)
+        from .splicing_utils import run_splicing_engine
+        donor_probs, acceptor_probs = run_splicing_engine(seq, engine)
+        # Trim off the fixed flanks before returning results.
+        seq = seq[5000:-5000]
+        indices = indices[5000:-5000]
+        df = pd.DataFrame({
+            'position': indices,
+            'donor_prob': donor_probs,
+            'acceptor_prob': acceptor_probs,
+            'nucleotides': list(seq)
+        }).set_index('position').round(3)
+        # if reference_donors is not None:
+        #     df['ref_donor'] = df.index.isin(reference_donors).astype(int)
+        # if reference_acceptors is not None:
+        #     df['ref_acceptor'] = df.index.isin(reference_acceptors).astype(int)
+
+        df.attrs['name'] = self.name
+        if inplace:
+            self.predicted_splicing = df
+            return self
+        else:
+            return df
+

{geney-1.4.16.dist-info → geney-1.4.18.dist-info}/METADATA

@@ -1,6 +1,6 @@
 Metadata-Version: 2.1
 Name: geney
-Version: 1.4.16
+Version: 1.4.18
 Summary: A Python package for gene expression modeling.
 Home-page: https://github.com/nicolaslynn/geney
 Author: Nicolas Lynn

{geney-1.4.16.dist-info → geney-1.4.18.dist-info}/RECORD

@@ -3,15 +3,15 @@ geney/Gene.py,sha256=6x1sEZV50Il4oydegW6iHIF12EZTGexniG3YUD-3DfM,7036
 geney/Oncosplice.py,sha256=ETAvMl_Oq6mEJQHPNwdDO5csX6Ahuped_om10KifCyM,17739
 geney/SeqMats.py,sha256=9-eJnfU2w3LGc0XvVvFEO_QrBneTkC6xkZKDfTcEw5o,19282
 geney/SpliceSimulator.py,sha256=iF6feVeSnsKFmn3WV60CgWLI0_rSLgpq5fVFL1IOv_4,18491
-geney/Transcript.py,sha256=Ltlcnp93s3HxMiweUuyc4Ri3QT42l1qUtiBYH3RITFs,14464
+geney/Transcript.py,sha256=_DhKQ-UnyFDPb4Cu-8sQPWvLd-kKj4ZEJq6KBntFVGE,14467
 geney/__init__.py,sha256=YLWXJS53yeryp6nVhCgFg3_Du9Guj9y3iSrdfx61q5Y,3017
 geney/_config_setup.py,sha256=nblcGU3HIt8YjdrAoGfbEVKRxwJKv0PikJ5-7AL6axQ,723
 geney/_graphic_utils.py,sha256=oMsBpB9YeEn96gGpKh4MmtagJffWZbk-xPrIwHvkFhA,11016
 geney/_gtex_utils.py,sha256=asL2lHyU5KsbWpV096vkf1Ka7hSo_RRfZqw7p5nERmE,1919
 geney/_immune_utils.py,sha256=b-8dRcCti7xsU7RG3op18lkSnAD8dp_BymGaR-hbNcI,5272
 geney/_mutation_utils.py,sha256=dHssUsnii_mf-wuRoMmF13UlD7k3ml_VwQMItTYnXpU,1132
-geney/_oncosplice.py,sha256=UkGPJqHSKK_XVsDp-03Baa3ks5ePb_1f1EB0wbkKrDo,35527
-geney/_splicing_utils.py,sha256=Zda6MD0e81p46_y6A240W97d1TP4dakLhG2WT0kSN5U,31473
+geney/_oncosplice.py,sha256=qrIqo3HAZAnzhtIGgv7EnwCE5YkdTFSwWoiSZLBzCpg,35530
+geney/_splicing_utils.py,sha256=7j5YC9CrWWFfct8hDdXyxYIqRtCPI4TqxA1cyAMhyy8,31476
 geney/_survival_utils.py,sha256=KnAzEviMuXh6SnVXId9PgsFLSbgkduTvYoIthxN7FPA,6886
 geney/_tcga_utils.py,sha256=uJhVnTbTysj0XrEw_YeDKRSLexsqgBLYQdhl7_hnr64,17611
 geney/_tis_utils.py,sha256=la0CZroaKe5RgAyFd4Bf_DqQncklWgAY2823xVst98o,7813
@@ -37,7 +37,8 @@ geney/translation_initiation/tis_utils.py,sha256=AF3siFjuQH-Rs44EV-80zHdbxRMvN4w
 geney/translation_initiation/resources/kozak_pssm.json,sha256=pcd0Olziutq-6H3mFWDCD9cujQ_AlZO-iiOvBl82hqE,1165
 geney/translation_initiation/resources/tis_regressor_model.joblib,sha256=IXb4DUDhJ5rBDKcqMk9zE3ECTZZcdj7Jixz3KpoZ7OA,2592025
 geney/utils/Fasta_segment.py,sha256=weB5NJ65P0XiyAJCiCHx4T9sHC1pWLpuQeOy0B85gyg,11364
-geney/utils/SeqMats.py,sha256=syRU5DAuTh3xUfGW_qP9wlcBO5pHsG_y5PlrfXTIxUY,18502
+geney/utils/SeqMats.py,sha256=2tJYPGy-cCCaANRbiYkki5yNxnhgzysDQGWjRYRSnlQ,8767
+geney/utils/SeqMatsOld.py,sha256=syRU5DAuTh3xUfGW_qP9wlcBO5pHsG_y5PlrfXTIxUY,18502
 geney/utils/TranscriptLibrary.py,sha256=ma_ZVPgglxXDDneEvdqxxeqxG8eSFL-zgLUXyC6BqY8,2070
 geney/utils/__init__.py,sha256=-nJ-DMx1JzP-ZCe_QuQCeM0ZYIT_16jxoXDhUaO_4Oc,714
 geney/utils/mutation_utils.py,sha256=r-pHr56gEa5kh_DPX8MjFY3ZfYaOtyo4CUfJ5ZHlXPw,3243
@@ -45,7 +46,7 @@ geney/utils/pangolin_utils.py,sha256=JQSPbWxdzqGFYfWQktkfLMaMSGR28eGQhNzO7MLMe5M
 geney/utils/spliceai_utils.py,sha256=VtrIbjyQxk_3lw86eWjftRYyal9OzxArJ0GV5u_ymTg,2721
 geney/utils/splicing_utils.py,sha256=vPCGnCPR1ooEZEHR79yFHLmRQXEJHXEQjjxpBR-YWOs,20635
 geney/utils/utils.py,sha256=m51Vd0cEbrcIHo6_8BAuI9YSPcKRs22e5LfVd2Qj6Is,2181
-geney-1.4.16.dist-info/METADATA,sha256=xkiO4TiMvtTYt5mdvs2hSOw-ijetjvNf0-MLyX-9poU,990
-geney-1.4.16.dist-info/WHEEL,sha256=AHX6tWk3qWuce7vKLrj7lnulVHEdWoltgauo8bgCXgU,109
-geney-1.4.16.dist-info/top_level.txt,sha256=O-FuNUMb5fn9dhZ-dYCgF0aZtfi1EslMstnzhc5IIVo,6
-geney-1.4.16.dist-info/RECORD,,
+geney-1.4.18.dist-info/METADATA,sha256=WLdB6CQyOBWNDYLU05Gyj6o7kaNzA5qr7ROD0mzTgm4,990
+geney-1.4.18.dist-info/WHEEL,sha256=AHX6tWk3qWuce7vKLrj7lnulVHEdWoltgauo8bgCXgU,109
+geney-1.4.18.dist-info/top_level.txt,sha256=O-FuNUMb5fn9dhZ-dYCgF0aZtfi1EslMstnzhc5IIVo,6
+geney-1.4.18.dist-info/RECORD,,