# LA4SR: illuminating the dark proteome with generative AI

arXiv: https://arxiv.org/abs/2411.06798 · HTML: https://mlsanity.com/paper/2411.06798/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 22 of its 68 references that are in the map.
- First posted on arXiv 11 Nov 2024.

## Builds on (most cited first, 22 of 22)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [LoRA: Low-Rank Adaptation of Large Language Models](https://mlsanity.com/paper/2106.09685/) (2021)
- [RoBERTa: A Robustly Optimized BERT Pretraining Approach](https://mlsanity.com/paper/1907.11692/) (2019)
- [Mamba: Linear-Time Sequence Modeling with Selective State Spaces](https://mlsanity.com/paper/2312.00752/) (2023)
- [DistilBERT, a distilled version of BERT: smaller, faster, cheaper and lighter](https://mlsanity.com/paper/1910.01108/) (2019)
- [QLoRA: Efficient Finetuning of Quantized LLMs](https://mlsanity.com/paper/2305.14314/) (2023)
- [Axiomatic Attribution for Deep Networks](https://mlsanity.com/paper/1703.01365/) (2017)
- [Mistral 7B](https://mlsanity.com/paper/2310.06825/) (2023)
- [UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction](https://mlsanity.com/paper/1802.03426/) (2018)
- [BLOOM: A 176B-Parameter Open-Access Multilingual Language Model](https://mlsanity.com/paper/2211.05100/) (2022)
- [Pythia: A Suite for Analyzing Large Language Models Across Training and Scaling](https://mlsanity.com/paper/2304.01373/) (2023)
- [MiniLM: Deep Self-Attention Distillation for Task-Agnostic Compression of Pre-Trained Transformers](https://mlsanity.com/paper/2002.10957/) (2020)
- [Learning Important Features Through Propagating Activation Differences](https://mlsanity.com/paper/1704.02685/) (2017)
- [On Large-Batch Training for Deep Learning: Generalization Gap and Sharp Minima](https://mlsanity.com/paper/1609.04836/) (2016)
- [Transformers are SSMs: Generalized Models and Efficient Algorithms Through Structured State Space Duality](https://mlsanity.com/paper/2405.21060/) (2024)
- [GPT-NeoX-20B: An Open-Source Autoregressive Language Model](https://mlsanity.com/paper/2204.06745/) (2022)
- [Speech Recognition with Deep Recurrent Neural Networks](https://mlsanity.com/paper/1303.5778/) (2013)
- [Eliciting Latent Predictions from Transformers with the Tuned Lens](https://mlsanity.com/paper/2303.08112/) (2023)
- [Captum: A unified and generic model interpretability library for PyTorch](https://mlsanity.com/paper/2009.07896/) (2020)
- [ByT5: Towards a token-free future with pre-trained byte-to-byte models](https://mlsanity.com/paper/2105.13626/) (2021)
- [Measuring the Effects of Data Parallelism on Neural Network Training](https://mlsanity.com/paper/1811.03600/) (2018)

## Abstract (arXiv)

AI language models (LMs) show promise for biological sequence analysis. We re-engineered open-source LMs (GPT-2, BLOOM, DistilRoBERTa, ELECTRA, and Mamba, ranging from 70M to 12B parameters) for microbial sequence classification. The models achieved F1 scores up to 95 and operated 16,580x faster and at 2.9x the recall of BLASTP. They effectively classified the algal dark proteome - uncharacterized proteins comprising about 65% of total proteins - validated on new data including a new, complete Hi-C/Pacbio Chlamydomonas genome. Larger (>1B) LA4SR models reached high accuracy (F1 > 86) when trained on less than 2% of available data, rapidly achieving strong generalization capacity. High accuracy was achieved when training data had intact or scrambled terminal information, demonstrating robust generalization to incomplete sequences. Finally, we provide custom AI explainability software tools for attributing amino acid patterns to AI generative processes and interpret their outputs in evolutionary and biophysical contexts.