Organizations: Case Western Reserve University Cleveland, Ohio, USA · The University of Texas Health Science Center at Houston Houston, Texas, USA · Rutgers University Newark, New Jersey, USA
Genomic language models (GLMs) have emerged as powerful tools for learning representations of DNA sequences, enabling advances in variant prediction, regulatory element identification, and cross-task transfer learning. However, as these models are increasingly trained or fine-tuned on sensitive genomic cohorts, they risk memorizing specific sequences from their training data, raising serious concerns around privacy, data leakage, and regulatory compliance. Despite growing awareness of memorization risks in general-purpose language models, little systematic evaluation exists for these risks in the genomic domain, where data exhibit unique properties such as a fixed nucleotide alphabet, strong biological structure, and individual identifiability. We present a comprehensive, multi-vector privacy evaluation framework designed to quantify memorization risks in GLMs. Our approach integrates three complementary risk assessment methodologies: perplexity-based detection, canary sequence extraction, and membership inference. These are combined into a unified evaluation pipeline that produces a worst-case memorization risk score. To enable controlled evaluation, we plant canary sequences at varying repetition rates into both synthetic and real genomic datasets, allowing precise quantification of how repetition and training dynamics influence memorization. We evaluate our framework across multiple GLM architectures, examining the relationship between sequence repetition, model capacity, and memorization risk. Our results establish that GLMs exhibit measurable memorization and that the degree of memorization varies across architectures and training regimes. These findings reveal that no single attack vector captures the full scope of memorization risk, underscoring the need for multi-vector privacy auditing as a standard practice for genomic AI systems.
Figures & tables
Figure 1. Overview of the memorization risk quantification framework. Genomic training data is augmented with canary sequences at controlled repetition rates (left), used to fine-tune a genomic language model (center), and evaluated through three complementary vectors: perplexity-based detection, canary sequence extraction, and membership inference (right). The outputs are combined into a maximum vulnerability score (bottom).
Model
Architecture
Params
FT
Tokenization
SimpleDNALM
Causal Transformer
12.9M
Full
Character-level
DNABERT-2
BERT Encoder
117M
Full
BPE
HyenaDNA
Hyena (Conv)
14.2M
Full
Single-nucleotide
Evo
StripedHyena (SSM)
7B
LoRA
Byte-level
Table 1. Models evaluated. FT = fine-tuning strategy.
Dataset
Source
Organism
Biological Structure
Synthetic
Generated
—
None (zero-order)
E. coli
NCBI RefSeq
E. coli K-12
Prokaryotic
Yeast
NCBI RefSeq
S. cerevisiae S288C
Eukaryotic
GUE
HuggingFace
Multi-species
Promoter regions
Table 2. Datasets evaluated across all model types.
Synthetic
E. coli
Yeast
GUE
Model
sppl
sext
smia
Sconfig
sppl
sext
smia
Sconfig
sppl
sext
smia
Sconfig
sppl
sext
smia
Sconfig
Smodel
SimpleDNALM
.02
.50
.52
.53 ± .02
.01
.45
.47
.48 ± .00
.00
.48
.49
.50 ± .02
.00
.51
.45
.51 ± .04
.55 ± .01
DNABERT-2
.35
.14
.48
.48 ± .02
.34
.14
.43
.43 ± .01
.38
.17
.45
.45 ± .02
.38
.09
.45
.45 ± .01
.48 ± .01
HyenaDNA
-.36
.23
.48
.48 ± .01
-1.04
.15
.49
.49 ± .01
-.05
.15
.49
.49 ± .01
-.90
.21
.47
.47 ± .01
.49 ± .00
Evo (LoRA)
.20
.67
.48
.82 ± .23
.34
1.00
.57
1.00 ± .00
.33
1.00
.50
1.00 ± .00
.34
1.00
.40
1.00 ± .00
1.00 ± .00
Table 3. Per-vector memorization risk scores and maximum vulnerability scores for each model-dataset configuration. Component scores ( sppl,sext,smia ) are reported as average across seeds. Sconfig and Smodel are computed per seed as the maximum of the component scores for that seed, then reported as mean ± std across seeds. Bold indicates the maximum vector driving Sconfig .
Figure 2. Canary extraction success rate as a function of repetition tier across datasets. Evo (LoRA) achieves near-complete extraction on real genomic data regardless of repetition count, while DNABERT-2 remains resistant.
Model
Dataset
Train
Test
Canary
Gap
SimpleDNALM
Synthetic
3.93 ± 0.00
4.00 ± 0.00
3.93 ± 0.01
1.02 ± 0.00
E. coli
3.91 ± 0.00
3.94 ± 0.00
3.91 ± 0.01
1.01 ± 0.00
Yeast
3.84 ± 0.02
3.86 ± 0.00
3.84 ± 0.02
1.00 ± 0.01
GUE
3.82 ± 0.03
3.84 ± 0.01
3.83 ± 0.02
1.00 ± 0.00
DNABERT-2
Synthetic
1.75 ± 0.00
2.69 ± 0.04
1.74 ± 0.00
1.54 ± 0.02
E. coli
1.68 ± 0.03
2.51 ± 0.03
1.66 ± 0.01
1.51 ± 0.02
Table 4. Mean perplexity across data splits and memorization gap ratio (test divided by canary perplexity) reported as average ± std across seeds. Gap >1.0 indicates the model assigns lower perplexity to canaries than to test sequences, signaling memorization.
Model
Synthetic
E. coli
Yeast
GUE
SimpleDNALM
0.76 ± 0.01
0.74 ± 0.00
0.75 ± 0.01
0.72 ± 0.00
DNABERT-2
0.74 ± 0.01
0.71 ± 0.01
0.73 ± 0.01
0.72 ± 0.01
HyenaDNA
0.74 ± 0.00
0.74 ± 0.00
0.74 ± 0.00
0.73 ± 0.01
Evo (LoRA)
0.74 ± 0.01
0.79 ± 0.02
0.75 ± 0.00
0.70 ± 0.01
Table 5. Membership inference AUC-ROC via likelihood ratio attack (mean ± std). AUC = 0.5 indicates random guessing; AUC = 1.0 indicates perfect membership discrimination.
Appendix figures & tables8 assets
Supplementary material from the paper’s appendix.
Appendix
Component
Configuration
Vocabulary size
8 (A, C, G, T + special tokens)
Hidden dimension
512
Attention heads
8
Transformer layers
4
Feedforward dimension
2048
Dropout
0.05
Appendix
Table 6. SimpleDNALM architectural specification.
Figure 3. Sconfig per seed for each model-dataset configuration. Each point represents one seed. Evo (LoRA) separates sharply on real genomic datasets while exhibiting high variance on synthetic data. The remaining models cluster tightly with low cross-seed variance.
Model
Seed 42
Seed 123
Seed 456
Mean ± Std
SimpleDNALM
0.55
0.57
0.54
0.55 ± 0.01
DNABERT-2
0.50
0.47
0.48
0.48 ± 0.01
HyenaDNA
0.49
0.49
0.49
0.49 ± 0.00
Evo (LoRA)
1.00
1.00
1.00
1.00 ± 0.00
Appendix
Table 7. Smodel per seed. Each value represents the maximum Sconfig across all four datasets for a given model and seed.
Model
Dataset
Seed
sppl
sext
smia
Sconfig
SimpleDNALM
Synthetic
42
0.0201
0.5300
0.5538
0.5538
123
0.0172
0.4300
0.5077
0.5077
456
0.0200
0.5400
0.5071
0.5400
E. coli
42
0.0085
0.4500
0.4703
0.4703
123
0.0085
0.4100
0.4791
0.4791
456
0.0096
0.4800
0.4611
0.4800
Appendix
Table 8. Full results across all models, datasets, and seeds. Sconfig is the maximum of sppl , sext , and smia for each configuration.
Dataset
Feature
AUC
Synthetic
shannon_entropy
0.504±0.001
gc_content
0.509±0.012
sequence_length
0.506±0.005
nucleotide_freq_variance
0.496±0.001
dinucleotide_chi2
0.491±0.015
trinucleotide_complexity
0.491±0.007
Appendix
Table 9. Per-feature membership inference AUC scores for the canary detectability analysis across all four evaluation datasets. Each feature is evaluated independently as a membership signal; LR_combined denotes the likelihood-ratio classifier combining all features. Values reported as mean ± std across three random seeds.
Hyperparameter
SimpleDNALM
DNABERT-2
HyenaDNA
Evo
Max sequence length
512
512
512
512
Max epochs
50
50
50
25
Batch size
8
8
8
4
Learning rate
2e−5
2e−5
2e−5
5e−5
Weight decay
0.01
0.01
0.01
0.01
Warmup ratio
0.1
0.1
0.1
0.1
Appendix
Table 10. Full training hyperparameters by model. All models use AdamW with weight decay of 0.01, warmup ratio of 0.1, gradient clipping at norm 1.0, and early stopping with patience 5 and δmin=0.001 .
Figure 4. Canary extraction success rate as a function of length.
Model
Dataset
Len
Train
Test
Canary
Gap
MIA
SimpleDNALM
Synthetic
32
3.92
4.00
3.92
1.02
0.75
SimpleDNALM
Synthetic
64
3.93
4.00
3.92
1.02
0.78
SimpleDNALM
Synthetic
128
3.96
4.01
3.96
1.01
0.76
SimpleDNALM
E. coli
32
3.88
3.94
3.88
1.02
0.74
SimpleDNALM
E. coli
64
3.91
3.95
3.91
1.01
0.74
SimpleDNALM
E. coli
128
3.94
3.96
3.94
1.00
0.75
Appendix
Table 11. Perplexity statistics, gap ratio (test/canary), and membership inference AUC by canary length.