Author name cluster

Joshua Meier

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

4 papers

2 author rows

NeurIPS Conference 2021 Conference Paper

Language models enable zero-shot prediction of the effects of mutations on protein function

Joshua Meier
Roshan Rao
Robert Verkuil
Jason Liu
Tom Sercu
Alex Rives

Modeling the effect of sequence variation on function is a fundamental problem for understanding and designing proteins. Since evolution encodes information about function into patterns in protein sequences, unsupervised models of variant effects can be learned from sequence data. The approach to date has been to fit a model to a family of related sequences. The conventional setting is limited, since a new model must be trained for each prediction task. We show that using only zero-shot inference, without any supervision from experimental data or additional training, protein language models capture the functional effects of sequence variation, performing at state-of-the-art.

PDF Details

ICML Conference 2021 Conference Paper

MSA Transformer

Roshan Rao
Jason Liu
Robert Verkuil
Joshua Meier
John F. Canny
Pieter Abbeel
Tom Sercu
Alexander Rives

Unsupervised protein language models trained across millions of diverse sequences learn structure and function of proteins. Protein language models studied to date have been trained to perform inference from individual sequences. The longstanding approach in computational biology has been to make inferences from a family of evolutionarily related sequences by fitting a model to each family independently. In this work we combine the two paradigms. We introduce a protein language model which takes as input a set of sequences in the form of a multiple sequence alignment. The model interleaves row and column attention across the input sequences and is trained with a variant of the masked language modeling objective across many protein families. The performance of the model surpasses current state-of-the-art unsupervised structure learning methods by a wide margin, with far greater parameter efficiency than prior state-of-the-art protein language models.

Details

ICLR Conference 2021 Conference Paper

Transformer protein language models are unsupervised structure learners

Roshan Rao
Joshua Meier
Tom Sercu
Sergey Ovchinnikov
Alexander Rives

Unsupervised contact prediction is central to uncovering physical, structural, and functional constraints for protein structure determination and design. For decades, the predominant approach has been to infer evolutionary constraints from a set of related sequences. In the past year, protein language models have emerged as a potential alternative, but performance has fallen short of state-of-the-art approaches in bioinformatics. In this paper we demonstrate that Transformer attention maps learn contacts from the unsupervised language modeling objective. We find the highest capacity models that have been trained to date already outperform a state-of-the-art unsupervised contact prediction pipeline, suggesting these pipelines can be replaced with a single forward pass of an end-to-end model.

Details

ICLR Conference 2020 Conference Paper

Energy-based models for atomic-resolution protein conformations

Yilun Du
Joshua Meier
Jerry Ma
Rob Fergus
Alexander Rives

We propose an energy-based model (EBM) of protein conformations that operates at atomic scale. The model is trained solely on crystallized protein data. By contrast, existing approaches for scoring conformations use energy functions that incorporate knowledge of physical principles and features that are the complex product of several decades of research and tuning. To evaluate the model, we benchmark on the rotamer recovery task, the problem of predicting the conformation of a side chain from its context within a protein structure, which has been used to evaluate energy functions for protein design. The model achieves performance close to that of the Rosetta energy function, a state-of-the-art method widely used in protein structure prediction and design. An investigation of the model’s outputs and hidden representations finds that it captures physicochemical properties relevant to protein energy.

Details