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DNABERT-2: Efficient Foundation Model and Benchmark For Multi-Species Genomes

ICLR 2024 · Probabilistic and scientific modeling › Molecules and proteins · approach: Biological sequence transformers · 173 citations (OpenAlex)

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Replaces k-mer tokenization with BPE in a multi-species genome foundation model (DNABERT-2) and introduces the GUE benchmark of 36 datasets across 9 tasks, matching NT-2500M-multi with 21x fewer parameters.

Problem

k-mer tokenization in genome language models causes information leakage, poor sample efficiency, and high computational cost, and existing genome benchmarks are non-standardized and either too easy or too hard.

Approach

Adapt SentencePiece BPE tokenization (non-overlapping, variable-length tokens) for DNA, combined with ALiBi, FlashAttention, GEGLU and an MLM objective pretrained on multi-species genomes, plus a calibrated multi-species classification benchmark (GUE/GUE+).

Key results

Measured effects reported in the paper

What was changedWhereMeasuredEffect
Replace K-mer tokenization with BPE (ablation)DNABERT-2 · GUE (28 datasets)average score: 60.92 -> 65.33Helped
Further pre-train on the GUE training sets (ablation)DNABERT-2 · GUE (28 datasets)average score: 66.80 -> 67.77Helped
Further pre-train on GUE training sets (ablation)DNABERT-2 · GUE taskstask scoreMixed
Replace BPE tokenization with K-mer tokenization (ablation)DNABERT-2 · GUE (28 datasets)average score: 65.33 -> 60.92Hurt

Surprising findings

Limitations

Experimental setup

Datasets: Multi-species genome (135 species) Human genome (DNABERT pretraining set) GUE GUE+ Epigenetic marks data (Nucleotide Transformer)

Benchmarks: GUE GUE+

Metrics: F1-score Matthews Correlation Coefficient parameters FLOPs

Baselines: DNABERT (3/4/5/6-mer) Nucleotide Transformer (NT-500M-human) NT-500M-1000g NT-2500M-1000g NT-2500M-multi HyenaDNA CNN

Builds on: DNABERT SentencePiece Byte Pair Encoding ALiBi FlashAttention

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