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Michael Heinzinger

Publications and source records attributed to Michael Heinzinger.

2 recordsLinked to original sources

From Words to Amino Acids: Does the Curse of Depth Persist?

Protein language models (PLMs) have become widely adopted as general-purpose models, demonstrating strong performance in protein engineering and de novo design. Like large language models (LLMs), they are typically trained as deep transformers with next-token or masked-token prediction objectives on massive sequence corpora and are scaled by increasing model depth. Recent work on autoregressive LLMs has identified the Curse of Depth: many later layers contribute little to the final output predictions. These findings naturally raise the question of whether a similar depth inefficiency also appears in PLMs, where many widely used models are not autoregressive, and some are multimodal, accepting both protein sequence and structure as input. In this work, we present a depth analysis of seven popular PLM families across model scales, spanning autoregressive, masked, and diffusion objectives, and quantify how layer contributions evolve with depth using a unified set of probing-, perturbation-, and downstream-evaluation measurements. Across models, we observe consistent depth-dependent patterns that extend prior findings on LLMs: a large fraction of task-relevant computation is concentrated in a subset of layers, while the remaining layers mainly provide incremental refinement of the final prediction. These trends persist beyond sequence-only settings and also appear in multimodal PLMs. Taken together, our results suggest that depth inefficiency is a common feature of modern PLMs, motivating future work on more depth-efficient architectures and training methods.

cs.LG

ProtTrans: Towards Cracking the Language of Life's Code Through Self-Supervised Deep Learning and High Performance Computing

Computational biology and bioinformatics provide vast data gold-mines from protein sequences, ideal for Language Models taken from NLP. These LMs reach for new prediction frontiers at low inference costs. Here, we trained two auto-regressive models (Transformer-XL, XLNet) and four auto-encoder models (BERT, Albert, Electra, T5) on data from UniRef and BFD containing up to 393 billion amino acids. The LMs were trained on the Summit supercomputer using 5616 GPUs and TPU Pod up-to 1024 cores. Dimensionality reduction revealed that the raw protein LM-embeddings from unlabeled data captured some biophysical features of protein sequences. We validated the advantage of using the embeddings as exclusive input for several subsequent tasks. The first was a per-residue prediction of protein secondary structure (3-state accuracy Q3=81%-87%); the second were per-protein predictions of protein sub-cellular localization (ten-state accuracy: Q10=81%) and membrane vs. water-soluble (2-state accuracy Q2=91%). For the per-residue predictions the transfer of the most informative embeddings (ProtT5) for the first time outperformed the state-of-the-art without using evolutionary information thereby bypassing expensive database searches. Taken together, the results implied that protein LMs learned some of the grammar of the language of life. To facilitate future work, we released our models at https://github.com/agemagician/ProtTrans.

cs.LG