变异效应与蛋白质稳定性：参数与补充说明

用法和示例见功能教程。

各功能按作用、API、输入、输出、示例代码和结果说明介绍。运行前按说明准备凭据、本地文件与可选依赖；远程结果随数据库版本与查询时间变化。

这些入口调用已有模型或预测服务。模型权重、SDK、服务凭据和使用条件继续由原提供方决定；DNAKit 没有重新训练这些模型。

各功能按作用、API、输入、输出、示例代码和结果说明介绍。运行前按说明准备凭据、本地文件与可选依赖；远程结果随数据库版本与查询时间变化。

评估变异对基因组调控轨道的影响

dnakit.databases.alpha_genome_score_variant(*, chromosome, position, reference_bases, alternate_bases, output_type=None, organism=None, sequence_length=None, top_n=None, verbose=True)

参数	类型	必填 / 默认值	说明与约束
chromosome	string	必填	Chromosome, e.g. 'chr22'.
position	integer	必填	1-based variant position.
reference_bases	string	必填	Reference allele, e.g. 'A'.
alternate_bases	string	必填	Alternate allele, e.g. 'C'.
output_type	string | null	None	Modality to score: RNA_SEQ (default), ATAC, DNASE, CAGE, CHIP_HISTONE, CHIP_TF, SPLICE_SITES, CONTACT_MAPS.
organism	string | null	None	'human' (default) or 'mouse'.
sequence_length	string | null	None	Context window: 16KB, 100KB, 500KB, or 1MB (default).
top_n	integer | null	None	Number of top |effect| tracks to return (default 20).
verbose	bool	True	运行提示开关。

运行前配置：ALPHA_GENOME_API_KEY。

预测氨基酸突变对蛋白质稳定性的影响

dnakit.databases.dyna_mut2_predict_stability(*, operation=None, pdb_id, chain, mutation, verbose=True)

参数	类型	必填 / 默认值	说明与约束
operation	string	None	Operation type
pdb_id	string	必填	4-character PDB accession code from RCSB PDB (e.g., '4HHB' for hemoglobin, '1U46' for ACK1 kinase). The structure will be downloaded automatically.
chain	string	必填	Chain identifier in the PDB structure (e.g., 'A'). Must be a valid chain in the specified PDB entry.
mutation	string	必填	Single-point mutation in the format WtPosNew where Wt is the wild-type amino acid (1-letter code), Pos is the residue number, and New is the mutant amino acid (1-letter code). Examples: 'V1A' (Val1Ala), 'E346K' (Glu346Lys), 'G12D' (Gly12Asp).
verbose	bool	True	运行提示开关。

使用 ESM-2 评估错义变异效应

dnakit.databases.esm2_score_missense_variant(*, sequence, position, mutant, wild_type=None, model_id=None, wait_for_model=None, verbose=True)

参数	类型	必填 / 默认值	说明与约束
sequence	string	必填	Wild-type protein sequence in 1-letter amino-acid code (whitespace is ignored).
position	integer	必填	1-based residue position of the variant within the sequence.
mutant	string	必填	Mutant amino acid (single 1-letter code, one of the 20 standard residues).
wild_type	string | null	None	Optional wild-type residue (1-letter). If given, it is validated against the residue at position to catch coordinate/sequence mismatches.
model_id	string | null	None	ESM-2 model to use. Default 'facebook/esm2_t33_650M_UR50D'. Other sizes: esm2_t30_150M_UR50D, esm2_t12_35M_UR50D, esm2_t6_8M_UR50D.
wait_for_model	boolean | null	None	If true, block until the model finishes loading on the HF servers instead of returning a retryable 'loading' status.
verbose	bool	True	运行提示开关。

汇总变异引起的蛋白质特征扰动机制

dnakit.databases.esm_explain_variant_mechanism(*, sequence, position, ref_aa, alt_aa, window=None, top_k_features=None, include_descriptions=None, model=None, sae_model=None, verbose=True)

参数	类型	必填 / 默认值	说明与约束
sequence	string	必填	Reference (wild-type) protein amino acid sequence in single-letter code. Up to ~2700 AA.
position	integer	必填	1-indexed residue position of the variant
ref_aa	string	必填	Single-letter wild-type amino acid (must match sequence[position-1])
alt_aa	string	必填	Single-letter substituted amino acid
window	integer	None	Residue window centered on the mutation for activation summation.
top_k_features	integer	None	Number of top lost / top gained features to describe and include in the category summary.
include_descriptions	boolean	None	If true (default), call ESM_describe_sae_feature on each top feature to get category labels. If false, return raw feature IDs without categories (cheaper).
model	string	None	ESMC base model
sae_model	string	None	SAE codebook identifier
verbose	bool	True	运行提示开关。

运行前配置：ESM_API_KEY。

批量评估错义变异的稀疏特征扰动

dnakit.databases.esm_score_variant_sae_batch(*, sequence, variants, window=None, top_k_features=None, model=None, sae_model=None, verbose=True)

参数	类型	必填 / 默认值	说明与约束
sequence	string	必填	Reference (wild-type) protein amino acid sequence in single-letter code. Up to ~2700 AA.
variants	array	必填	List of variants to score. Each variant: {position: 1-indexed int, ref_aa: single letter matching sequence[position-1], alt_aa: single letter substitution}. {"maxItems": 100, "items": {"type": "object", "properties": {"position": {"type": "integer", "description": "1-indexed residue position"}, "ref_aa": {"type": "string", "description": "Single-letter wild-type amino acid (must match sequence[position-1])"}, "alt_aa": {"type": "string", "description": "Single-letter substituted amino acid"}}, "required": ["position", "ref_aa", "alt_aa"]}}
window	integer	None	Residue window centered on each variant for activation summation. Default 8 (i.e. positions [pos-8, pos+8]).
top_k_features	integer	None	Number of top features to return per variant (top-K lost + top-K gained).
model	string	None	ESMC base model (must be the 6B model — SAEs are trained against it)
sae_model	string	None	SAE codebook identifier
verbose	bool	True	运行提示开关。

运行前配置：ESM_API_KEY。

比较参考与突变蛋白质的稀疏特征

dnakit.databases.esm_score_variant_sae_disruption(*, sequence, position, ref_aa, alt_aa, window=None, top_k_features=None, model=None, sae_model=None, verbose=True)

参数	类型	必填 / 默认值	说明与约束
sequence	string	必填	Reference protein sequence (canonical isoform). Single-letter codes, no gaps. The mutant sequence is built internally by substituting alt_aa at position.
position	integer	必填	1-indexed mutation position. The amino acid at sequence[position-1] must equal ref_aa; otherwise the tool returns an error (the wrong sequence was supplied or the variant notation references a different isoform).
ref_aa	string	必填	Reference amino acid at the mutation position, single-letter code (e.g. 'R'). Tool validates this matches the supplied sequence.
alt_aa	string	必填	Mutant amino acid, single-letter code (e.g. 'H' for R175H).
window	integer	None	Residue window radius around the mutation. Per-feature activations are summed across this window before computing the delta. Default 8 = +/- 8 residues = 17-residue window.
top_k_features	integer	None	Number of top LOST and top GAINED features to return. Default 10.
model	string	None	ESMC backbone (default esmc-6b-2024-12).
sae_model	string	None	SAE checkpoint (default layer-60 6B SAE).
verbose	bool	True	运行提示开关。

运行前配置：ESM_API_KEY。

使用 Evo 2 评估 DNA 变异效应

dnakit.databases.evo2_score_variant(*, ref_sequence=None, alt_sequence=None, sequence=None, position=None, reference=None, alternate=None, model=None, verbose=True)

参数	类型	必填 / 默认值	说明与约束
ref_sequence	string | null	None	Reference DNA window (A/C/G/T/N). Use with alt_sequence (same length).
alt_sequence	string | null	None	Alternate DNA window, same length/centering as ref_sequence.
sequence	string | null	None	Reference DNA window for point-substitution mode (use with position + alternate).
position	integer | null	None	1-based position of the substituted base within sequence.
reference	string | null	None	Optional reference base (single letter) at position, validated against sequence.
alternate	string | null	None	Alternate base (single letter) substituted at position.
model	string	None	Hosted Evo 2 model size: evo2-40b (default, most accurate) or evo2-7b (smaller, faster).
verbose	bool	True	运行提示开关。

运行前配置：NVIDIA_API_KEY。

查询变异的最大 SpliceAI 剪接变化分数

dnakit.databases.splice_ai_get_max_delta(*, variant, genome=None, verbose=True)

参数	类型	必填 / 默认值	说明与约束
variant	string	必填	Variant in chr-pos-ref-alt format (e.g., chr8-140300616-T-G)
genome	string	None	Genome build: 37 or 38 (default: 38)
verbose	bool	True	运行提示开关。

使用 Pangolin 预测变异的剪接影响

dnakit.databases.splice_ai_predict_pangolin(*, variant, genome=None, distance=None, mask=None, verbose=True)

参数	类型	必填 / 默认值	说明与约束
variant	string	必填	Variant in chr-pos-ref-alt format (e.g., chr8-140300616-T-G)
genome	string	None	Genome build: 37 or 38 (default: 38)
distance	integer	None	Distance parameter for model (default: 1000)
mask	boolean	None	Use masked scores
verbose	bool	True	运行提示开关。

使用 SpliceAI 预测剪接位点变化

dnakit.databases.splice_ai_predict_splice(*, variant, genome=None, distance=None, mask=None, verbose=True)

参数	类型	必填 / 默认值	说明与约束
variant	string	必填	Variant in chr-pos-ref-alt format (e.g., chr8-140300616-T-G) or colon-separated
genome	string	None	Genome build: 37 (GRCh37/hg19) or 38 (GRCh38/hg38). Default: 38
distance	integer	None	Distance parameter for model (default: 50). Larger values capture more distal effects.
mask	boolean	None	Use masked scores (recommended for variant interpretation). Raw scores better for alternative splicing analysis.
verbose	bool	True	运行提示开关。