In the field of artificial intelligence, a combination of scale in data and model capacity enabled by unsupervised learning has led to major advances in representation learning and statistical generation. In the life sciences, the anticipated growth of sequencing promises unprecedented data on natural sequence diversity. Protein language modeling at the scale of evolution is a logical step toward predictive and generative artificial intelligence for biology. To this end, we use unsupervised learning to train a deep contextual language model on 86 billion amino acids across 250 million protein sequences spanning evolutionary diversity. The resulting model contains information about biological properties in its representations. The representations are learned from sequence data alone. The learned representation space has a multiscale organization reflecting structure from the level of biochemical properties of amino acids to remote homology of proteins. Information about secondary and tertiary structure is encoded in the representations and can be identified by linear projections. Representation learning produces features that generalize across a range of applications, enabling state-of-the-art supervised prediction of mutational effect and secondary structure and improving state-of-the-art features for long-range contact prediction.

In the field of artificial intelligence, a combination of scale in data and model capacity enabled by unsupervised learning has led to major advances in representation learning and statistical generation. In biology, the anticipated growth of sequencing promises unprecedented data on natural sequence diversity. Learning the natural distribution of evolutionary protein sequence variation is a logical step toward predictive and generative modeling for biology. To this end we use unsupervised learning to train a deep contextual language model on 86 billion amino acids across 250 million sequences spanning evolutionary diversity. The resulting model maps raw sequences to representations of biological properties without labels or prior domain knowledge. The learned representation space organizes sequences at multiple levels of biological granularity from the biochemical to proteomic levels. Unsupervised learning recovers information about protein structure: secondary structure and residue-residue contacts can be identified by linear projections from the learned representations. Training language models on full sequence diversity rather than individual protein families increases recoverable information about secondary structure. The unsupervised models can be adapted with supervision from quantitative mutagenesis data to predict variant activity. Predictions from sequences alone are comparable to results from a state-of-the-art model of mutational effects that uses evolutionary and structurally derived features.

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Momentum-based acceleration of stochastic gradient descent (SGD) is widely used in deep learning. We propose the quasi-hyperbolic momentum algorithm (QHM) as an extremely simple alteration of momentum SGD, averaging a plain SGD step with a momentum step. We describe numerous connections to and identities with other algorithms, and we characterize the set of two-state optimization algorithms that QHM can recover. Finally, we propose a QH variant of Adam called QHAdam, and we empirically demonstrate that our algorithms lead to significantly improved training in a variety of settings, including a new state-of-theart result on WMT16 EN-DE. We hope that these empirical results, combined with the conceptual and practical simplicity of QHM and QHAdam, will spur interest from both practitioners and researchers. Code is immediately available. 1