We measure the effects of a weak language model, estimated from as little as 100k words of text, on unsupervised acoustic model training and then explore the best method of using word confidences to estimate n-gram counts for unsupervised language model training. Even with 100k words of text and 10 hours of training data, unsupervised acoustic modeling is robust, with 50% of the gain recovered when compared to supervised training. For language model training, multiplying the word confidences together to get a weighted count produces the best reduction in WER by 2% over the baseline language model and 0.5% absolute over using unweighted transcripts. Oracle experiments show that a larger gain is possible, but better confidence estimation techniques are needed to identify correct n-grams.

Engineered proteins generally must possess a stable structure in order to achieve their designed function. Stable designs, however, are astronomically rare within the space of all possible amino acid sequences. As a consequence, many designs must be tested computationally and experimentally in order to find stable ones, which is expensive in terms of time and resources. Here we use a high-throughput, low-fidelity assay to experimentally evaluate the stability of approximately 200,000 novel proteins. These include a wide range of sequence perturbations, providing a baseline for future work in the field. We build a neural network model that predicts protein stability given only sequences of amino acids, and compare its performance to the assayed values. We also report another network model that is able to generate the amino acid sequences of novel stable proteins given requested secondary sequences. Finally, we show that the predictive model—despite weaknesses including a noisy data set—can be used to substantially increase the stability of both expert-designed and model-generated proteins.

Engineered proteins generally must possess a stable structure in order to achieve their designed function. Stable designs, however, are astronomically rare within the space of all possible amino acid sequences. As a consequence, many designs must be tested computationally and experimentally in order to find stable ones, which is expensive in terms of time and resources. Here we report a neural network model that predicts protein stability based only on sequences of amino acids, and demonstrate its performance by evaluating the stability of almost 200,000 novel proteins. These include a wide range of sequence perturbations, providing a baseline for future work in the field. We also report a second neural network model that is able to generate novel stable proteins. Finally, we show that the predictive model can be used to substantially increase the stability of both expert-designed and model-generated proteins.

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