ProtTrans: Toward Understanding the Language of Life Through Self-Supervised Learning

Ahmed Elnaggar, Michael Heinzinger, Christian Dallago, Ghalia Rehawi, Yu Wang, Llion Jones, Tom Gibbs, Tamas Feher, Christoph Angerer, Martin Steinegger, Debsindhu Bhowmik, Burkhard Rost

Abstract: Computational biology and bioinformatics provide vast data gold-mines from protein sequences, ideal for Language Models (LMs) taken from Natural Language Processing (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 protein LMs (pLMs) were trained on the Summit supercomputer using 5616 GPUs and TPU Pod up-to 1024 cores. Dimensionality reduction revealed that the raw pLM- <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">embeddings</i> from unlabeled data captured some biophysical features of protein sequences. We validated the advantage of using the <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">embeddings</i> as exclusive input for several subsequent tasks: (1) a per-residue (per-token) prediction of protein secondary structure (3-state accuracy Q3=81%-87%); (2) per-protein (pooling) predictions of protein sub-cellular location (ten-state accuracy: Q10=81%) and membrane versus water-soluble (2-state accuracy Q2=91%). For secondary structure, the most informative embeddings (ProtT5) for the first time outperformed the state-of-the-art without multiple sequence alignments (MSAs) or evolutionary information thereby bypassing expensive database searches. Taken together, the results implied that pLMs learned some of the <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">grammar</i> of the <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">language of life</i> . All our models are available through <uri xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">https://github.com/agemagician/ProtTrans</uri> .