Author name cluster

Tom Sercu

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.

8 papers

2 author rows

ICML Conference 2022 Conference Paper

Learning inverse folding from millions of predicted structures

Chloe Hsu
Robert Verkuil
Jason Liu
Zeming Lin
Brian Hie
Tom Sercu
Adam Lerer
Alexander Rives

We consider the problem of predicting a protein sequence from its backbone atom coordinates. Machine learning approaches to this problem to date have been limited by the number of available experimentally determined protein structures. We augment training data by nearly three orders of magnitude by predicting structures for 12M protein sequences using AlphaFold2. Trained with this additional data, a sequence-to-sequence transformer with invariant geometric input processing layers achieves 51% native sequence recovery on structurally held-out backbones with 72% recovery for buried residues, an overall improvement of almost 10 percentage points over existing methods. The model generalizes to a variety of more complex tasks including design of protein complexes, partially masked structures, binding interfaces, and multiple states.

Details

AAAI Conference 2021 Conference Paper

Improved Mutual Information Estimation

Youssef Mroueh
Igor Melnyk
Pierre Dognin
Jarret Ross
Tom Sercu

We propose to estimate the KL divergence using a relaxed likelihood ratio estimation in a Reproducing Kernel Hilbert space. We show that the dual of our ratio estimator for KL in the particular case of Mutual Information estimation corresponds to a lower bound on the MI that is related to the so called Donsker Varadhan lower bound. In this dual form, MI is estimated via learning a witness function discriminating between the joint density and the product of marginal, as well as an auxiliary scalar variable that enforces a normalization constraint on the likelihood ratio. By extending the function space to neural networks, we propose an efficient neural MI estimator, and validate its performance on synthetic examples, showing advantage over the existing baselines. We demonstrate its strength in large-scale self-supervised representation learning through MI maximization.

PDF Details

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

NeurIPS Conference 2019 Conference Paper

Sobolev Independence Criterion

Youssef Mroueh
Tom Sercu
Mattia Rigotti
Inkit Padhi
Cicero Nogueira dos Santos

We propose the Sobolev Independence Criterion (SIC), an interpretable dependency measure between a high dimensional random variable X and a response variable Y. SIC decomposes to the sum of feature importance scores and hence can be used for nonlinear feature selection. SIC can be seen as a gradient regularized Integral Probability Metric (IPM) between the joint distribution of the two random variables and the product of their marginals. We use sparsity inducing gradient penalties to promote input sparsity of the critic of the IPM. In the kernel version we show that SIC can be cast as a convex optimization problem by introducing auxiliary variables that play an important role in feature selection as they are normalized feature importance scores. We then present a neural version of SIC where the critic is parameterized as a homogeneous neural network, improving its representation power as well as its interpretability. We conduct experiments validating SIC for feature selection in synthetic and real-world experiments. We show that SIC enables reliable and interpretable discoveries, when used in conjunction with the holdout randomization test and knockoffs to control the False Discovery Rate. Code is available at http: //github. com/ibm/sic.

PDF Details

NeurIPS Conference 2017 Conference Paper

Fisher GAN

Youssef Mroueh
Tom Sercu

Generative Adversarial Networks (GANs) are powerful models for learning complex distributions. Stable training of GANs has been addressed in many recent works which explore different metrics between distributions. In this paper we introduce Fisher GAN that fits within the Integral Probability Metrics (IPM) framework for training GANs. Fisher GAN defines a data dependent constraint on the second order moments of the critic. We show in this paper that Fisher GAN allows for stable and time efficient training that does not compromise the capacity of the critic, and does not need data independent constraints such as weight clipping. We analyze our Fisher IPM theoretically and provide an algorithm based on Augmented Lagrangian for Fisher GAN. We validate our claims on both image sample generation and semi-supervised classification using Fisher GAN.

PDF Details

ICML Conference 2017 Conference Paper

McGan: Mean and Covariance Feature Matching GAN

Youssef Mroueh
Tom Sercu
Vaibhava Goel

We introduce new families of Integral Probability Metrics (IPM) for training Generative Adversarial Networks (GAN). Our IPMs are based on matching statistics of distributions embedded in a finite dimensional feature space. Mean and covariance feature matching IPMs allow for stable training of GANs, which we will call McGan. McGan minimizes a meaningful loss between distributions.

Details