modeling_esm_plusplus.py

"""
ESM++ model implementation.

ESM++ is a faithful implementation of ESMC that allows for batching and standard Huggingface compatibility
The ESM Python package is not required

Modified from https://github.com/evolutionaryscale/esm
License: https://www.evolutionaryscale.ai/policies/cambrian-non-commercial-license-agreement
"""

import math
import os
import torch
import torch.nn as nn
import torch.nn.functional as F
from dataclasses import dataclass
from functools import cache, partial
from pathlib import Path
from typing import Optional, Tuple, Union
from einops import rearrange, repeat
from huggingface_hub import snapshot_download
from tokenizers import Tokenizer
from tokenizers.models import BPE
from tokenizers.processors import TemplateProcessing
from torch.utils.data import Dataset, DataLoader
from tqdm.auto import tqdm
from transformers import PreTrainedModel, PreTrainedTokenizerFast, PretrainedConfig
from transformers.modeling_outputs import ModelOutput


class ESMplusplusConfig(PretrainedConfig):
    """Configuration class for ESM++ model.
    
    Args:
        vocab_size: Size of the vocabulary
        hidden_size: Dimension of hidden layers
        num_attention_heads: Number of attention heads
        num_hidden_layers: Number of transformer layers
        num_labels: Number of output labels for classification
        problem_type: Type of problem - regression, single/multi label classification
    """
    model_type = "ESMplusplus"
    def __init__(
        self,
        vocab_size: int = 64,
        hidden_size: int = 960,
        num_attention_heads: int = 15,
        num_hidden_layers: int = 30,
        num_labels: int = 2,
        problem_type: str | None = None,
        dropout: float = 0.0,
        initializer_range: float = 0.02,
        **kwargs,
    ):
        super().__init__(**kwargs)
        self.vocab_size = vocab_size
        self.hidden_size = hidden_size
        self.num_attention_heads = num_attention_heads
        self.num_hidden_layers = num_hidden_layers
        self.num_labels = num_labels
        self.problem_type = problem_type
        self.dropout = dropout
        self.initializer_range = initializer_range


### Rotary Embeddings
def rotate_half(x: torch.Tensor, interleaved: bool = False) -> torch.Tensor:
    """Rotates half the hidden dims of the input."""
    if not interleaved:
        x1, x2 = x.chunk(2, dim=-1)
        return torch.cat((-x2, x1), dim=-1)
    else:
        x1, x2 = x[..., ::2], x[..., 1::2]
        return rearrange(
            torch.stack((-x2, x1), dim=-1), "... d two -> ... (d two)", two=2
        )


def apply_rotary_emb_torch(
    x: torch.Tensor,
    cos: torch.Tensor,
    sin: torch.Tensor,
    interleaved: bool = False,
    _inplace: bool = False,
) -> torch.Tensor:
    """Apply rotary embeddings to input based on cos and sin."""
    ro_dim = cos.shape[-1] * 2
    assert ro_dim <= x.shape[-1]
    seqlen = x.size(1)
    cos = cos[:seqlen]
    sin = sin[:seqlen]
    cos = repeat(cos, "s d -> s 1 (2 d)")
    sin = repeat(sin, "s d -> s 1 (2 d)")
    return torch.cat(
        [
            x[..., :ro_dim] * cos + rotate_half(x[..., :ro_dim], interleaved) * sin,
            x[..., ro_dim:],
        ],
        dim=-1,
    )


class RotaryEmbedding(torch.nn.Module):
    """Rotary position embeddings.
    
    Based on the paper "RoFormer: Enhanced Transformer with Rotary Position Embedding"
    
    Args:
        dim: Dimension of the embedding
        base: Base for computing angular frequencies
        interleaved: Whether to use interleaved rotations
        scale_base: Base for scaling
        scaling_factor: Factor for scaling positions
        pos_idx_in_fp32: Whether to compute position indices in fp32
        device: Computation device
    """
    def __init__(
        self,
        dim: int,
        base: float = 10000.0,
        interleaved: bool = False,
        scale_base: Optional[float] = None,
        scaling_factor: float = 1.0,
        pos_idx_in_fp32: bool = True,
        device: Optional[torch.device] = None,
    ):
        super().__init__()
        self.dim = dim
        self.base = float(base)
        self.pos_idx_in_fp32 = pos_idx_in_fp32
        self.interleaved = interleaved
        self.scale_base = scale_base
        self.scaling_factor = scaling_factor
        self.device = device

        self._seq_len_cached = 0
        self._cos_cached = None
        self._sin_cached = None
        self._cos_k_cached = None
        self._sin_k_cached = None
        self.reset_parameters()

    def reset_parameters(self):
        """Reset the parameters of the embedding."""
        inv_freq = self._compute_inv_freq(self.device)
        self.register_buffer("inv_freq", inv_freq, persistent=False)
        arange = torch.arange(0, self.dim, 2, device=self.device, dtype=torch.float32)
        scale = (
            (arange + 0.4 * self.dim) / (1.4 * self.dim)
            if self.scale_base is not None
            else None
        )
        self.register_buffer("scale", scale)

    def _compute_inv_freq(self, device: Optional[torch.device] = None) -> torch.Tensor:
        """Compute inverse frequency bands."""
        return 1 / (
            self.base
            ** (
                torch.arange(0, self.dim, 2, device=device, dtype=torch.float32)
                / self.dim
            )
        )

    def _update_cos_sin_cache(self, seqlen: int, device: Optional[torch.device] = None, dtype: Optional[torch.dtype] = None):
        """Update the cached cosine and sine values."""
        if (
            seqlen > self._seq_len_cached
            or self._cos_cached is None
            or self._cos_cached.device != device
            or self._cos_cached.dtype != dtype
            or (self.training and self._cos_cached.is_inference())
        ):
            self._seq_len_cached = seqlen
            if self.pos_idx_in_fp32:
                t = torch.arange(seqlen, device=device, dtype=torch.float32)
                t /= self.scaling_factor
                if self.inv_freq.dtype != torch.float32:
                    inv_freq = self.inv_freq.to(torch.float32)
                else:
                    inv_freq = self.inv_freq
            else:
                t = torch.arange(seqlen, device=device, dtype=self.inv_freq.dtype)
                t /= self.scaling_factor
                inv_freq = self.inv_freq
            freqs = torch.outer(t, inv_freq)

            if self.scale is None:
                self._cos_cached = torch.cos(freqs).to(dtype)
                self._sin_cached = torch.sin(freqs).to(dtype)
            else:
                power = (
                    torch.arange(
                        seqlen, dtype=self.scale.dtype, device=self.scale.device
                    )
                    - seqlen // 2
                ) / self.scale_base
                scale = self.scale.to(device=power.device) ** power.unsqueeze(-1)
                self._cos_cached = (torch.cos(freqs) * scale).to(dtype)
                self._sin_cached = (torch.sin(freqs) * scale).to(dtype)
                self._cos_k_cached = (torch.cos(freqs) / scale).to(dtype)
                self._sin_k_cached = (torch.sin(freqs) / scale).to(dtype)

    def forward(self, q: torch.Tensor, k: torch.Tensor) -> Tuple[torch.Tensor, torch.Tensor]:
        """Apply rotary embeddings to queries and keys.
        
        Args:
            q: Query tensor of shape (batch, seqlen, nheads, headdim)
            k: Key tensor of shape (batch, seqlen, nheads, headdim)
            
        Returns:
            Tuple of rotated query and key tensors
        """
        self._update_cos_sin_cache(q.shape[1], device=q.device, dtype=q.dtype)
        assert self._cos_cached is not None
        assert self._sin_cached is not None
        if self.scale is None:
            return (
                apply_rotary_emb_torch(
                    q,
                    self._cos_cached,
                    self._sin_cached,
                    self.interleaved,
                    True,  # inplace=True
                ),
                apply_rotary_emb_torch(
                    k,
                    self._cos_cached,
                    self._sin_cached,
                    self.interleaved,
                    True,  # inplace=True
                ),
            )  # type: ignore
        else:
            assert False


### Feedforward Network Components
def swiglu_correction_fn(expansion_ratio: float, d_model: int) -> int:
    """Compute corrected dimension for SwiGLU."""
    return int(((expansion_ratio * d_model) + 255) // 256 * 256)


class SwiGLU(nn.Module):
    """SwiGLU activation function."""
    def __init__(self):
        super(SwiGLU, self).__init__()

    def forward(self, x: torch.Tensor) -> torch.Tensor:
        x1, x2 = x.chunk(2, dim=-1)
        return F.silu(x1) * x2


def swiglu_ln_ffn(d_model: int, expansion_ratio: float) -> nn.Sequential:
    """Create SwiGLU feedforward network with layer normalization."""
    return nn.Sequential(
        nn.LayerNorm(d_model),
        nn.Linear(
            d_model, swiglu_correction_fn(expansion_ratio, d_model) * 2, bias=False
        ),
        SwiGLU(),
        nn.Linear(swiglu_correction_fn(expansion_ratio, d_model), d_model, bias=False),
    )


### Attention
class MultiHeadAttention(nn.Module):
    """Multi-head attention with rotary embeddings.
    
    Args:
        d_model: Model dimension
        n_heads: Number of attention heads
    """
    def __init__(self, d_model: int, n_heads: int):
        super().__init__()
        self.d_model = d_model
        self.n_heads = n_heads
        self.d_head = self.d_model // self.n_heads
        self.layernorm_qkv = nn.Sequential(
            nn.LayerNorm(d_model), nn.Linear(d_model, d_model * 3, bias=False)
        )
        self.out_proj = nn.Linear(d_model, d_model, bias=False)
        self.q_ln = nn.LayerNorm(d_model, bias=False)
        self.k_ln = nn.LayerNorm(d_model, bias=False)
        self.reshaper = partial(rearrange, pattern="b s (h d) -> b h s d", h=n_heads)
        self.rotary = RotaryEmbedding(d_model // n_heads)

    def _apply_rotary(self, q: torch.Tensor, k: torch.Tensor) -> Tuple[torch.Tensor, torch.Tensor]:
        """Apply rotary embeddings to query and key."""
        q = q.unflatten(-1, (self.n_heads, self.d_head))
        k = k.unflatten(-1, (self.n_heads, self.d_head))
        q, k = self.rotary(q, k)
        q = q.flatten(-2, -1)
        k = k.flatten(-2, -1)
        return q, k

    def forward(self, x: torch.Tensor, attention_mask: Optional[torch.Tensor] = None, output_attentions: bool = False) -> Union[torch.Tensor, Tuple[torch.Tensor, torch.Tensor]]:
        """
        Args:
            x: Input tensor
            attention_mask: Optional attention mask
            output_attentions: Whether to return attention weights
            
        Returns:
            Output tensor after self attention, and optionally attention weights
        """
        attn_weights = None
        qkv_BLD3 = self.layernorm_qkv(x)
        query_BLD, key_BLD, value_BLD = torch.chunk(qkv_BLD3, 3, dim=-1)
        query_BLD, key_BLD = (
            self.q_ln(query_BLD).to(query_BLD.dtype),
            self.k_ln(key_BLD).to(query_BLD.dtype),
        )
        query_BLD, key_BLD = self._apply_rotary(query_BLD, key_BLD)
        query_BHLD, key_BHLD, value_BHLD = map(self.reshaper, (query_BLD, key_BLD, value_BLD))

        if output_attentions: # Manual attention computation
            L, S = query_BLD.size(-2), key_BLD.size(-2)
            scale = 1 / math.sqrt(query_BLD.size(-1))
            attn_bias = torch.zeros(L, S, dtype=query_BLD.dtype, device=query_BLD.device)
            if attention_mask is not None:
                if attention_mask.dtype == torch.bool:
                    attention_mask.masked_fill_(attention_mask.logical_not(), float('-inf'))
                else:
                    attn_bias += attention_mask
    
            attn_weights = torch.matmul(query_BHLD, key_BHLD.transpose(-2, -1)) * scale
            attn_weights += attn_bias
            attn_weights = F.softmax(attn_weights, dim=-1)
            context_BHLD = torch.matmul(attn_weights, value_BHLD)
        else:
            context_BHLD = F.scaled_dot_product_attention(
                query_BHLD, key_BHLD, value_BHLD, attention_mask
            )
            
        context_BLD = rearrange(context_BHLD, "b h s d -> b s (h d)")
        output = self.out_proj(context_BLD)
        return output, attn_weights


### Regression Head
def RegressionHead(d_model: int, output_dim: int, hidden_dim: Optional[int] = None) -> nn.Module:
    """Create a regression head with optional hidden dimension.
    
    Args:
        d_model: Input dimension
        output_dim: Output dimension
        hidden_dim: Optional hidden dimension (defaults to d_model)
    """
    hidden_dim = hidden_dim if hidden_dim is not None else d_model
    return nn.Sequential(
        nn.Linear(d_model, hidden_dim),
        nn.GELU(),
        nn.LayerNorm(hidden_dim),
        nn.Linear(hidden_dim, output_dim),
    )


### Transformer Block
class UnifiedTransformerBlock(nn.Module):
    """Transformer block with attention and feedforward layers.
    
    Args:
        d_model: Model dimension
        n_heads: Number of attention heads
        residue_scaling_factor: Factor for scaling residual connections
        expansion_ratio: Expansion ratio for feedforward network
    """
    def __init__(
        self,
        d_model: int,
        n_heads: int,
        residue_scaling_factor: float = 1,
        expansion_ratio: float = 8 / 3,
        dropout: float = 0.0,
    ):
        super().__init__()
        self.attn = MultiHeadAttention(d_model, n_heads)
        self.ffn = swiglu_ln_ffn(d_model, expansion_ratio)
        self.scaling_factor = residue_scaling_factor
        self.dropout = nn.Dropout(dropout)

    def forward(
        self,
        x: torch.Tensor,
        attention_mask: Optional[torch.Tensor] = None,
        output_attentions: bool = False,
    ) -> Union[torch.Tensor, Tuple[torch.Tensor, torch.Tensor]]:
        """
        Args:
            x: Input tensor
            attention_mask: Optional attention mask
            output_attentions: Whether to return attention weights
            
        Returns:
            Output tensor after transformer block, and optionally attention weights
        """
        attn_output, attn_weights = self.attn(x, attention_mask, output_attentions)
        x = x + self.dropout(attn_output) / self.scaling_factor
        x = x + self.dropout(self.ffn(x)) / self.scaling_factor
        return x, attn_weights


### Model Outputs
@dataclass
class TransformerOutput(ModelOutput):
    """Output type for transformer encoder."""
    last_hidden_state: Optional[torch.Tensor] = None
    hidden_states: Optional[Tuple[torch.Tensor]] = None
    attentions: Optional[Tuple[torch.Tensor]] = None


@dataclass
class ESMplusplusOutput(ModelOutput):
    """Output type for ESM++ models."""
    loss: Optional[torch.Tensor] = None
    logits: Optional[torch.Tensor] = None
    last_hidden_state: Optional[torch.Tensor] = None
    hidden_states: Optional[Tuple[torch.Tensor]] = None
    attentions: Optional[Tuple[torch.Tensor]] = None


### Transformer Stack
class TransformerStack(nn.Module):
    """Stack of transformer blocks.
    
    Args:
        d_model: Model dimension
        n_heads: Number of attention heads
        n_layers: Number of transformer layers
        dropout: Dropout rate
    """
    def __init__(
        self,
        d_model: int,
        n_heads: int,
        n_layers: int,
        dropout: float = 0.0,
    ):
        super().__init__()
        self.blocks = nn.ModuleList(
            [
                UnifiedTransformerBlock(
                    d_model,
                    n_heads,
                    residue_scaling_factor=math.sqrt(n_layers / 36),
                    dropout=dropout,
                )
                for i in range(n_layers)
            ]
        )
        self.norm = nn.LayerNorm(d_model, bias=False)
        self.gradient_checkpointing = False

    def forward(
        self,
        x: torch.Tensor,
        attention_mask: Optional[torch.Tensor] = None,
        output_hidden_states: bool = False,
        output_attentions: bool = False,
    ) -> TransformerOutput:
        """
        Args:
            x: Input tensor
            attention_mask: Optional attention mask
            output_hidden_states: Whether to return all hidden states
            output_attentions: Whether to return attention weights
            
        Returns:
            TransformerOutput containing last hidden state and optionally all hidden states and attention weights
        """
        batch_size, seq_len, _ = x.shape
        hidden_states = () if output_hidden_states else None
        attentions = () if output_attentions else None
        
        if attention_mask is not None:
            attention_mask = attention_mask[:, None, None, :].expand(batch_size, 1, seq_len, seq_len).bool()
            
        for block in self.blocks:
            if self.gradient_checkpointing and self.training:
                x, attn_weights = self._gradient_checkpointing_func(
                    block.__call__,
                    x,
                    attention_mask,
                    output_attentions,
                )
            else:
                x, attn_weights = block(x, attention_mask, output_attentions)

            if attentions is not None:
                attentions += (attn_weights,)
                
            if output_hidden_states:
                assert hidden_states is not None
                hidden_states += (x,)
                
        return TransformerOutput(
            last_hidden_state=self.norm(x), 
            hidden_states=hidden_states,
            attentions=attentions
        )


### Dataset for Embedding
class ProteinDataset(Dataset):
    """Simple dataset for protein sequences."""
    def __init__(self, sequences: list[str]):
        self.sequences = sequences

    def __len__(self) -> int:
        return len(self.sequences)

    def __getitem__(self, idx: int) -> str:
        return self.sequences[idx]


class PreTrainedESMplusplusModel(PreTrainedModel):
    """
    init weights for ESM++ models
    """
    config_class = ESMplusplusConfig
    base_model_prefix = "esm++"
    supports_gradient_checkpointing = True

    def _init_weights(self, module):
        """Initialize the weights"""
        if isinstance(module, nn.Linear):
            module.weight.data.normal_(mean=0.0, std=self.config.initializer_range)
            if module.bias is not None:
                module.bias.data.zero_()
        elif isinstance(module, nn.Embedding):
            module.weight.data.normal_(mean=0.0, std=self.config.initializer_range)
            if module.padding_idx is not None:
                module.weight.data[module.padding_idx].zero_()
        elif isinstance(module, nn.LayerNorm):
            module.bias.data.zero_()
            module.weight.data.fill_(1.0)

    @classmethod
    def from_pretrained_esm(cls, model_name: str):
        """Load a pretrained ESM++ model."""
        if '300' in model_name:
            return ESMplusplus_300M()
        elif '600' in model_name:
            return ESMplusplus_600M()
        else:
            raise ValueError(f"Invalid model name: {model_name}")

    @property
    def device(self) -> torch.device:
        """Get the device of the model."""
        return next(self.parameters()).device

    def mean_pooling(self, x: torch.Tensor, attention_mask: Optional[torch.Tensor] = None) -> torch.Tensor:
        """Apply mean pooling to sequence outputs."""
        if attention_mask is None:
            return x.mean(dim=1)
        else:
            attention_mask = attention_mask.unsqueeze(-1)
            return (x * attention_mask).sum(dim=1) / attention_mask.sum(dim=1)
        
    def max_pooling(self, x: torch.Tensor, attention_mask: Optional[torch.Tensor] = None) -> torch.Tensor:
        """Apply max pooling to sequence outputs."""
        if attention_mask is None:
            return x.max(dim=1).values
        else:
            attention_mask = attention_mask.unsqueeze(-1)
            return (x * attention_mask).max(dim=1).values

    def cls_pooling(self, x: torch.Tensor, attention_mask: Optional[torch.Tensor] = None) -> torch.Tensor:
        """Apply cls pooling to sequence outputs."""
        return x[:, 0, :]

    def _collate_fn(self, sequences: list[str]) -> tuple[torch.Tensor, torch.Tensor]:
        """Collate function for batching sequences."""
        return self.tokenizer(sequences, return_tensors="pt", padding='longest', pad_to_multiple_of=8)

    def _read_sequences_from_db(self, db_path: str) -> set[str]:
        """Read sequences from SQLite database."""
        import sqlite3
        sequences = []
        with sqlite3.connect(db_path) as conn:
            c = conn.cursor()
            c.execute("SELECT sequence FROM embeddings")
            while True:
                row = c.fetchone()
                if row is None:
                    break
                sequences.append(row[0])
        return set(sequences)

    def embed_dataset(
        self,
        sequences: list[str],
        batch_size: int = 2,
        max_len: int = 512,
        full_embeddings: bool = False,
        full_precision: bool = False,
        pooling_type: str = 'mean',
        num_workers: int = 0,
        sql: bool = False,
        sql_db_path: str = 'embeddings.db',
    ) -> Optional[dict[str, torch.Tensor]]:
        """Embed a dataset of protein sequences.
        
        Args:
            sequences: List of protein sequences
            batch_size: Batch size for processing
            max_len: Maximum sequence length
            full_embeddings: Whether to return full residue-wise (True) embeddings or pooled (False)
            full_precision: Whether to cast to full precision (float32) before storage - relevant for dict storage
            pooling_type: Type of pooling ('mean' or 'cls')
            num_workers: Number of workers for data loading, 0 for the main process
            sql: Whether to store embeddings in SQLite database - will be stored in float32
            sql_db_path: Path to SQLite database
            
        Returns:
            Dictionary mapping sequences to embeddings, or None if sql=True
        """
        sequences = list(set([seq[:max_len] for seq in sequences]))
        sequences = sorted(sequences, key=len, reverse=True)
        dataset = ProteinDataset(sequences)
        dataloader = DataLoader(dataset, batch_size=batch_size, num_workers=num_workers, collate_fn=self._collate_fn)
        device = self.device

        def get_embeddings(residue_embeddings: torch.Tensor, attention_mask: Optional[torch.Tensor] = None) -> torch.Tensor:
            if full_embeddings:
                return residue_embeddings
            elif pooling_type == 'mean':
                return self.mean_pooling(residue_embeddings, attention_mask)
            elif pooling_type == 'max':
                return self.max_pooling(residue_embeddings, attention_mask)
            elif pooling_type == 'cls':
                return self.cls_pooling(residue_embeddings, attention_mask)
            else:
                raise ValueError(f"Invalid pooling type: {pooling_type}")

        if sql:
            import sqlite3
            conn = sqlite3.connect(sql_db_path)
            c = conn.cursor()
            c.execute('CREATE TABLE IF NOT EXISTS embeddings (sequence text PRIMARY KEY, embedding blob)')
            already_embedded = self._read_sequences_from_db(sql_db_path)
            to_embed = [seq for seq in sequences if seq not in already_embedded]
            print(f"Found {len(already_embedded)} already embedded sequences in {sql_db_path}")
            print(f"Embedding {len(to_embed)} new sequences")
            if len(to_embed) > 0:
                with torch.no_grad():
                    for i, batch in tqdm(enumerate(dataloader), total=len(dataloader), desc='Embedding batches'):
                        seqs = to_embed[i * batch_size:(i + 1) * batch_size]
                        input_ids, attention_mask = batch['input_ids'].to(device), batch['attention_mask'].to(device)
                        x = self.embed(input_ids)
                        residue_embeddings = self.transformer(x, attention_mask).last_hidden_state.detach().float() # required for sql
                        embeddings = get_embeddings(residue_embeddings, attention_mask)

                        for seq, emb, mask in zip(seqs, embeddings, attention_mask):
                            if full_embeddings:
                                emb = emb[mask.bool()]
                            c.execute("INSERT OR REPLACE INTO embeddings VALUES (?, ?)", 
                                    (seq, emb.cpu().numpy().tobytes()))
                        
                        if (i + 1) % 100 == 0:
                            conn.commit()
            
                conn.commit()
            conn.close()
            return None

        embeddings_dict = {}
        with torch.no_grad():
            for i, batch in tqdm(enumerate(dataloader), total=len(dataloader), desc='Embedding batches'):
                seqs = sequences[i * batch_size:(i + 1) * batch_size]
                input_ids, attention_mask = batch['input_ids'].to(device), batch['attention_mask'].to(device)
                x = self.embed(input_ids)
                residue_embeddings = self.transformer(x, attention_mask).last_hidden_state.detach()
                if full_precision:
                    residue_embeddings = residue_embeddings.float()
                embeddings = get_embeddings(residue_embeddings, attention_mask).cpu()
                for seq, emb in zip(seqs, embeddings):
                    embeddings_dict[seq] = emb
                    
        return embeddings_dict


### ESM++ Models
class ESMplusplusModel(PreTrainedESMplusplusModel):
    """
    ESM++ model. transformer model with no heads
    """
    config_class = ESMplusplusConfig
    def __init__(self, config: ESMplusplusConfig, **kwargs):
        super().__init__(config, **kwargs)
        self.config = config
        self.vocab_size = config.vocab_size
        self.embed = nn.Embedding(self.vocab_size, config.hidden_size)
        self.transformer = TransformerStack(config.hidden_size, config.num_attention_heads, config.num_hidden_layers, config.dropout)
        self.tokenizer = EsmSequenceTokenizer()
        self.init_weights()

    def get_input_embeddings(self):
        return self.embed

    def set_input_embeddings(self, value):
        self.embed = value

    def forward(
        self,
        input_ids: Optional[torch.Tensor] = None,
        attention_mask: Optional[torch.Tensor] = None,
        inputs_embeds: Optional[torch.Tensor] = None,
        output_attentions: Optional[bool] = None,
        output_hidden_states: Optional[bool] = None,
        return_dict: Optional[bool] = None, # to play nice with HF adjacent packages
    ) -> TransformerOutput:
        """Forward pass for masked language modeling.
        
        Args:
            input_ids: Input token IDs
            attention_mask: Attention mask
            inputs_embeds: Optional precomputed embeddings
            output_hidden_states: Whether to return all hidden states
            output_attentions: Whether to return attention weights
            
        Returns:
            TransformerOutput containing last hidden state and optionally all hidden states and attention weights
        """
        if inputs_embeds is None:
            x = self.embed(input_ids)
        else:
            x = inputs_embeds
        return self.transformer(x, attention_mask, output_hidden_states, output_attentions)
        

class ESMplusplusForMaskedLM(PreTrainedESMplusplusModel):
    """
    ESM++ model for masked language modeling.
    Implements the base ESM++ architecture with a masked language modeling head.
    """
    config_class = ESMplusplusConfig
    def __init__(self, config: ESMplusplusConfig, **kwargs):
        super().__init__(config, **kwargs)
        self.config = config
        self.vocab_size = config.vocab_size
        self.embed = nn.Embedding(self.vocab_size, config.hidden_size)
        self.transformer = TransformerStack(config.hidden_size, config.num_attention_heads, config.num_hidden_layers, config.dropout)
        self.sequence_head = RegressionHead(config.hidden_size, self.vocab_size)
        self.ce_loss = nn.CrossEntropyLoss()
        self.tokenizer = EsmSequenceTokenizer()
        self.init_weights()

    def get_input_embeddings(self):
        return self.embed

    def set_input_embeddings(self, value):
        self.embed = value

    def get_output_embeddings(self):
        return self.sequence_head[-1]

    def set_output_embeddings(self, new_embeddings):
        self.sequence_head[-1] = new_embeddings

    def forward(
        self,
        input_ids: Optional[torch.Tensor] = None,
        attention_mask: Optional[torch.Tensor] = None,
        inputs_embeds: Optional[torch.Tensor] = None,
        labels: Optional[torch.Tensor] = None,
        output_attentions: Optional[bool] = None,
        output_hidden_states: Optional[bool] = None,
        return_dict: Optional[bool] = None, # to play nice with HF adjacent packages
    ) -> ESMplusplusOutput:
        """Forward pass for masked language modeling.
        
        Args:
            input_ids: Input token IDs
            attention_mask: Attention mask
            inputs_embeds: Optional precomputed embeddings
            labels: Optional labels for masked tokens
            output_hidden_states: Whether to return all hidden states
            output_attentions: Whether to return attention weights
            
        Returns:
            ESMplusplusOutput containing loss, logits, hidden states and attention weights
        """
        if inputs_embeds is None:
            x = self.embed(input_ids)
        else:
            x = inputs_embeds
        output = self.transformer(x, attention_mask, output_hidden_states, output_attentions)
        x = output.last_hidden_state
        logits = self.sequence_head(x)
        loss = None
        if labels is not None:
            loss = self.ce_loss(logits.view(-1, self.vocab_size), labels.view(-1))
        return ESMplusplusOutput(
            loss=loss,
            logits=logits,
            last_hidden_state=x,
            hidden_states=output.hidden_states,
            attentions=output.attentions,
        )


class ESMplusplusForSequenceClassification(ESMplusplusForMaskedLM):
    """
    ESM++ model for sequence classification.
    Extends the base ESM++ model with a classification head.
    """
    def __init__(self, config: ESMplusplusConfig, **kwargs):
        super().__init__(config, **kwargs)
        self.config = config
        self.num_labels = config.num_labels
        self.classifier = RegressionHead(config.hidden_size * 2, config.num_labels, config.hidden_size * 4)
        # Large intermediate projections help with sequence classification tasks (*4)
        self.mse = nn.MSELoss()
        self.ce = nn.CrossEntropyLoss()
        self.bce = nn.BCEWithLogitsLoss()
        self.init_weights()

    def forward(
        self,
        input_ids: Optional[torch.Tensor] = None,
        attention_mask: Optional[torch.Tensor] = None,
        inputs_embeds: Optional[torch.Tensor] = None,
        labels: Optional[torch.Tensor] = None,
        output_attentions: Optional[bool] = None,
        output_hidden_states: Optional[bool] = None,
        return_dict: Optional[bool] = None, # to play nice with HF adjacent packages
    ) -> ESMplusplusOutput:
        """Forward pass for sequence classification.
        
        Args:
            input_ids: Input token IDs
            attention_mask: Attention mask
            inputs_embeds: Optional precomputed embeddings
            labels: Optional labels for classification
            output_hidden_states: Whether to return all hidden states
            output_attentions: Whether to return attention weights
            
        Returns:
            ESMplusplusOutput containing loss, logits, and hidden states
        """
        output = super().forward(
            input_ids=input_ids,
            attention_mask=attention_mask,
            inputs_embeds=inputs_embeds,
            labels=None,
            output_attentions=output_attentions,
            output_hidden_states=output_hidden_states
        )
        x = output.last_hidden_state
        cls_features = x[:, 0, :]
        mean_features = self.mean_pooling(x, attention_mask)
        # we include mean pooling features to help with early convergence, the cost of this is basically zero
        features = torch.cat([cls_features, mean_features], dim=-1)
        logits = self.classifier(features)
        loss = None
        if labels is not None:
            labels = labels.to(logits.device)
            if self.config.problem_type is None:
                if self.num_labels == 1:
                    self.config.problem_type = "regression"
                elif self.num_labels > 1 and (labels.dtype == torch.long or labels.dtype == torch.int):
                    self.config.problem_type = "single_label_classification"
                else:
                    self.config.problem_type = "multi_label_classification"

            if self.config.problem_type == "regression":
                if self.num_labels == 1:
                    loss = self.mse(logits.flatten(), labels.flatten())
                else:
                    loss = self.mse(logits, labels)
            elif self.config.problem_type == "single_label_classification":
                loss = self.ce(logits.view(-1, self.num_labels), labels.view(-1))
            elif self.config.problem_type == "multi_label_classification":
                loss = self.bce(logits, labels)
        return ESMplusplusOutput(
            loss=loss,
            logits=logits,
            last_hidden_state=x,
            hidden_states=output.hidden_states,
        )


class ESMplusplusForTokenClassification(ESMplusplusForMaskedLM):
    """
    ESM++ model for token classification.
    Extends the base ESM++ model with a token classification head.
    """
    def __init__(self, config: ESMplusplusConfig):
        super().__init__(config)
        self.config = config
        self.num_labels = config.num_labels
        self.classifier = RegressionHead(config.hidden_size, config.num_labels, config.hidden_size * 4)
        # Large intermediate projections help with sequence classification tasks (*4)
        self.loss_fct = nn.CrossEntropyLoss()
        self.init_weights()

    def forward(
        self,
        input_ids: Optional[torch.Tensor] = None,
        attention_mask: Optional[torch.Tensor] = None,
        inputs_embeds: Optional[torch.Tensor] = None,
        labels: Optional[torch.Tensor] = None,
        output_attentions: Optional[bool] = None,
        output_hidden_states: Optional[bool] = None,
        return_dict: Optional[bool] = None, # to play nice with HF adjacent packages
    ) -> ESMplusplusOutput:
        """Forward pass for token classification.
        
        Args:
            input_ids: Input token IDs
            attention_mask: Attention mask
            inputs_embeds: Optional precomputed embeddings
            labels: Optional labels for token classification
            output_hidden_states: Whether to return all hidden states
            output_attentions: Whether to return attention weights
            
        Returns:
            ESMplusplusOutput containing loss, logits, and hidden states
        """
        output = super().forward(
            input_ids=input_ids,
            attention_mask=attention_mask,
            inputs_embeds=inputs_embeds,
            labels=None,
            output_attentions=output_attentions,
            output_hidden_states=output_hidden_states
        )
        x = output.last_hidden_state
        logits = self.classifier(x)
        loss = None
        if labels is not None:
            loss = self.loss_fct(logits.view(-1, self.num_labels), labels.view(-1))
        return ESMplusplusOutput(
            loss=loss,
            logits=logits,
            last_hidden_state=x,
            hidden_states=output.hidden_states,
        )


### Loading from EvolutionaryScale
@staticmethod
@cache
def data_root(model: str):
    if "INFRA_PROVIDER" in os.environ:
        return Path("")
    # Try to download from hugginface if it doesn't exist
    if model.startswith("esmc-300"):
        path = Path(snapshot_download(repo_id="EvolutionaryScale/esmc-300m-2024-12"))
    elif model.startswith("esmc-600"):
        path = Path(snapshot_download(repo_id="EvolutionaryScale/esmc-600m-2024-12"))
    else:
        raise ValueError(f"{model=} is an invalid model name.")
    return path


def ESMplusplus_300M(device: torch.device | str = "cpu"):
    with torch.device(device):
        config = ESMplusplusConfig(
            hidden_size=960,
            num_attention_heads=15,
            num_hidden_layers=30,
        )
        model = ESMplusplusForMaskedLM(config)
    state_dict = torch.load(
        data_root("esmc-300") / "data/weights/esmc_300m_2024_12_v0.pth",
        map_location=device,
    )
    model.load_state_dict(state_dict)
    return model


def ESMplusplus_600M(device: torch.device | str = "cpu"):
    with torch.device(device):
        config = ESMplusplusConfig(
            hidden_size=1152,
            num_attention_heads=18,
            num_hidden_layers=36,
        )
        model = ESMplusplusForMaskedLM(config)
    state_dict = torch.load(
        data_root("esmc-600") / "data/weights/esmc_600m_2024_12_v0.pth",
        map_location=device,
    )
    model.load_state_dict(state_dict)
    return model


### Tokenization
SEQUENCE_VOCAB = [
    "<cls>", "<pad>", "<eos>", "<unk>",
    "L", "A", "G", "V", "S", "E", "R", "T", "I", "D", "P", "K",
    "Q", "N", "F", "Y", "M", "H", "W", "C", "X", "B", "U", "Z",
    "O", ".", "-", "|",
    "<mask>",
]

class EsmSequenceTokenizer(PreTrainedTokenizerFast):
    model_input_names = ["input_ids", "attention_mask"]

    def __init__(
        self,
        unk_token="<unk>",
        cls_token="<cls>",
        pad_token="<pad>",
        mask_token="<mask>",
        eos_token="<eos>",
        chain_break_token="|",
        **kwargs,
    ):
        all_tokens = SEQUENCE_VOCAB
        token_to_id = {tok: ind for ind, tok in enumerate(all_tokens)}

        # a character-level tokenizer is the same as BPE with no token merges
        bpe = BPE(token_to_id, merges=[], unk_token=unk_token)
        tokenizer = Tokenizer(bpe)
        special_tokens = [
            cls_token,
            pad_token,
            mask_token,
            eos_token,
            chain_break_token,
        ]
        self.cb_token = chain_break_token
        additional_special_tokens = [chain_break_token]

        tokenizer.add_special_tokens(special_tokens)

        # This is where we configure the automatic addition of special tokens when we call
        # tokenizer(text, add_special_tokens=True). Note that you can also configure how two
        # sequences are merged if you want.
        tokenizer.post_processor = TemplateProcessing(  # type: ignore
            single="<cls> $A <eos>",
            special_tokens=[
                ("<cls>", tokenizer.token_to_id("<cls>")),
                ("<eos>", tokenizer.token_to_id("<eos>")),
            ],
        )
        super().__init__(
            tokenizer_object=tokenizer,
            unk_token=unk_token,
            cls_token=cls_token,
            pad_token=pad_token,
            mask_token=mask_token,
            eos_token=eos_token,
            additional_special_tokens=additional_special_tokens,
            **kwargs,
        )

    # These are a footgun, we never use the `bos` token anywhere so we're just overriding it here.
    @property
    def bos_token(self):
        return self.cls_token

    @property
    def bos_token_id(self):
        return self.cls_token_id

    @property
    def chain_break_token(self):
        return self.cb_token

    @property
    def chain_break_token_id(self):
        return self.convert_tokens_to_ids(self.chain_break_token)

    @property
    def all_token_ids(self):
        return list(range(self.vocab_size))

    @property
    def special_token_ids(self):
        return self.all_special_ids