Stanislaw Jastrzebski

Generative Active Learning for the Search of Small-molecule Protein Binders

Maksym Korablyov

Cheng-Hao Liu

Moksh J. Jain

Almer M. van der Sloot

Eric Jolicoeur

Edward Ruediger

Andrei Cristian Nica

Emmanuel Bengio

Kostiantyn Lapchevskyi

Daniel St-Cyr

Doris Alexandra Schuetz

Victor I Butoi

Jarrid Rector-Brooks

Simon R. Blackburn

Leo Feng

Hadi Nekoei

Sai Krishna Gottipati

Priyesh Vijayan

Prateek Gupta

Ladislav Rampasek … (see 14 more)

Sasikanth Avancha

Pierre-Luc Bacon

William L. Hamilton

Brooks Paige

Sanchit Misra

Stanisław Jastrzębski

Bharat Kaul

Doina Precup

José Miguel Hernández-Lobato

Marwin Segler

Michael M. Bronstein

Anne Marinier

Mike Tyers

Yoshua Bengio

Despite substantial progress in machine learning for scientific discovery in recent years, truly de novo design of small molecules which exh… (see more)ibit a property of interest remains a significant challenge. We introduce LambdaZero, a generative active learning approach to search for synthesizable molecules. Powered by deep reinforcement learning, LambdaZero learns to search over the vast space of molecules to discover candidates with a desired property. We apply LambdaZero with molecular docking to design novel small molecules that inhibit the enzyme soluble Epoxide Hydrolase 2 (sEH), while enforcing constraints on synthesizability and drug-likeliness. LambdaZero provides an exponential speedup in terms of the number of calls to the expensive molecular docking oracle, and LambdaZero de novo designed molecules reach docking scores that would otherwise require the virtual screening of a hundred billion molecules. Importantly, LambdaZero discovers novel scaffolds of synthesizable, drug-like inhibitors for sEH. In in vitro experimental validation, a series of ligands from a generated quinazoline-based scaffold were synthesized, and the lead inhibitor N-(4,6-di(pyrrolidin-1-yl)quinazolin-2-yl)-N-methylbenzamide (UM0152893) displayed sub-micromolar enzyme inhibition of sEH.

2024-05-02

ArXiv (preprint)

doi.org

arxiv.org

Noisy Pairing and Partial Supervision for Stylized Opinion Summarization

Reinald Kim

Mirella Lapata. 2020

Un-611

Maxinder S. Kan-620

Somnath Basu

Roy Chowdhury

Chao Zhao

Tanya Goyal

Junyi Jiacheng Xu

Jessy Li

Ivor W. Tsang

James T. Kwok

Neil Houlsby

Andrei Giurgiu

Stanisław Jastrzębski … (see 22 more)

Bruna Morrone

Quentin de Laroussilhe

Mona Gesmundo

Attariyan Sylvain

Gelly

Thomas Wolf

Lysandre Debut

Julien Victor Sanh

Clement Chaumond

Anthony Delangue

Pier-339 Moi

Tim ric Cistac

R´emi Rault

Morgan Louf

Funtow-900 Joe

Sam Davison

Patrick Shleifer

Von Platen

Clara Ma

Yacine Jernite

Julien Plu

Canwen Xu

Opinion summarization research has primar-001 ily focused on generating summaries reflect-002 ing important opinions from customer reviews 0… (see more)03 without paying much attention to the writing 004 style. In this paper, we propose the stylized 005 opinion summarization task, which aims to 006 generate a summary of customer reviews in 007 the desired (e.g., professional) writing style. 008 To tackle the difficulty in collecting customer 009 and professional review pairs, we develop a 010 non-parallel training framework, Noisy Pair-011 ing and Partial Supervision ( NAPA ), which 012 trains a stylized opinion summarization sys-013 tem from non-parallel customer and profes-014 sional review sets. We create a benchmark P RO - 015 S UM by collecting customer and professional 016 reviews from Yelp and Michelin. Experimental 017 results on P RO S UM and FewSum demonstrate 018 that our non-parallel training framework con-019 sistently improves both automatic and human 020 evaluations, successfully building a stylized 021 opinion summarization model that can gener-022 ate professionally-written summaries from cus-023 tomer reviews. 024

2023-01-01

(published)

www.semanticscholar.org

RetroGNN: Fast Estimation of Synthesizability for Virtual Screening and De Novo Design by Learning from Slow Retrosynthesis Software

Cheng-Hao Liu

Maksym Korablyov

Stanisław Jastrzębski

Paweł Włodarczyk-Pruszyński

Yoshua Bengio

Marwin Segler

2022-04-22

Journal of Chemical Information and Modeling (published)

doi.org

RetroGNN: Approximating Retrosynthesis by Graph Neural Networks for De Novo Drug Design

Cheng-Hao Liu

Maksym Korablyov

Stanisław Jastrzębski

Paweł Włodarczyk-Pruszyński

Yoshua Bengio

Marwin Segler

De novo molecule generation often results in chemically unfeasible molecules. A natural idea to mitigate this problem is to bias the search … (see more)process towards more easily synthesizable molecules using a proxy for synthetic accessibility. However, using currently available proxies still results in highly unrealistic compounds. We investigate the feasibility of training deep graph neural networks to approximate the outputs of a retrosynthesis planning software, and their use to bias the search process. We evaluate our method on a benchmark involving searching for drug-like molecules with antibiotic properties. Compared to enumerating over five million existing molecules from the ZINC database, our approach finds molecules predicted to be more likely to be antibiotics while maintaining good drug-like properties and being easily synthesizable. Importantly, our deep neural network can successfully filter out hard to synthesize molecules while achieving a

2020-11-25

ArXiv (preprint)

arxiv.org

On the Relation Between the Sharpest Directions of DNN Loss and the SGD Step Length

Stanisław Jastrzębski

Amos Storkey

Stochastic Gradient Descent (SGD) based training of neural networks with a large learning rate or a small batch-size typically ends in well-… (see more)generalizing, flat regions of the weight space, as indicated by small eigenvalues of the Hessian of the training loss. However, the curvature along the SGD trajectory is poorly understood. An empirical investigation shows that initially SGD visits increasingly sharp regions, reaching a maximum sharpness determined by both the learning rate and the batch-size of SGD. When studying the SGD dynamics in relation to the sharpest directions in this initial phase, we find that the SGD step is large compared to the curvature and commonly fails to minimize the loss along the sharpest directions. Furthermore, using a reduced learning rate along these directions can improve training speed while leading to both sharper and better generalizing solutions compared to vanilla SGD. In summary, our analysis of the dynamics of SGD in the subspace of the sharpest directions shows that they influence the regions that SGD steers to (where larger learning rate or smaller batch size result in wider regions visited), the overall training speed, and the generalization ability of the final model.

2019-01-01

ICLR.cc/2019/Conference (poster)

openreview.net

Width of Minima Reached by Stochastic Gradient Descent is Influenced by Learning Rate to Batch Size Ratio

Stanisław Jastrzębski

Amos Storkey

2018-09-27

Artificial Neural Networks and Machine Learning – ICANN 2018 (published)

doi.org

Commonsense mining as knowledge base completion? A study on the impact of novelty

Stanisław Jastrzębski

Seyedarian Hosseini

Commonsense knowledge bases such as ConceptNet represent knowledge in the form of relational triples. Inspired by recent work by Li et al., … (see more)we analyse if knowledge base completion models can be used to mine commonsense knowledge from raw text. We propose novelty of predicted triples with respect to the training set as an important factor in interpreting results. We critically analyse the difficulty of mining novel commonsense knowledge, and show that a simple baseline method that outperforms the previous state of the art on predicting more novel triples.

2018-06-01

Proceedings of the Workshop on Generalization in the Age of Deep Learning (published)

doi.org

arxiv.org

Finding Flatter Minima with SGD

Stanisław Jastrzębski

Amos Storkey

2018-02-12

International Conference on Learning Representations (published)

dblp.uni-trier.de

SGD S MOOTHS THE S HARPEST D IRECTIONS

Stanisław Jastrzębski

Amos Storkey

Stochastic gradient descent (SGD) is able to find regions that generalize well, even in drastically over-parametrized models such as deep ne… (see more)ural networks. We observe that noise in SGD controls the spectral norm and conditioning of the Hessian throughout the training. We hypothesize the cause of this phenomenon is due to the dynamics of neurons saturating their non-linearity along the largest curvature directions, thus leading to improved conditioning.

2018-02-12

(published)

openreview.net

LATTER M INIMA WITH SGD

Stanisław Jastrzębski

Amos Storkey

LATTER M INIMA WITH SGD

Stanisław Jastrzębski

Amos Storkey

It has been discussed that over-parameterized deep neural networks (DNNs) trained using stochastic gradient descent (SGD) with smaller batch… (see more) sizes generalize better compared with those trained with larger batch sizes. Additionally, model parameters found by small batch size SGD tend to be in flatter regions. We extend these empirical observations and experimentally show that both large learning rate and small batch size contribute towards SGD finding flatter minima that generalize well. Conversely, we find that small learning rates and large batch sizes lead to sharper minima that correlate with poor generalization in DNNs.

2018-01-01

(published)

www.semanticscholar.org

Three Factors Influencing Minima in SGD

Stanisław Jastrzębski

Amos Storkey

We study the statistical properties of the endpoint of stochastic gradient descent (SGD). We approximate SGD as a stochastic differential eq… (see more)uation (SDE) and consider its Boltzmann Gibbs equilibrium distribution under the assumption of isotropic variance in loss gradients.. Through this analysis, we find that three factors – learning rate, batch size and the variance of the loss gradients – control the trade-off between the depth and width of the minima found by SGD, with wider minima favoured by a higher ratio of learning rate to batch size. In the equilibrium distribution only the ratio of learning rate to batch size appears, implying that it’s invariant under a simultaneous rescaling of each by the same amount. We experimentally show how learning rate and batch size affect SGD from two perspectives: the endpoint of SGD and the dynamics that lead up to it. For the endpoint, the experiments suggest the endpoint of SGD is similar under simultaneous rescaling of batch size and learning rate, and also that a higher ratio leads to flatter minima, both findings are consistent with our theoretical analysis. We note experimentally that the dynamics also seem to be similar under the same rescaling of learning rate and batch size, which we explore showing that one can exchange batch size and learning rate in a cyclical learning rate schedule. Next, we illustrate how noise affects memorization, showing that high noise levels lead to better generalization. Finally, we find experimentally that the similarity under simultaneous rescaling of learning rate and batch size breaks down if the learning rate gets too large or the batch size gets too small.

2017-11-13

ArXiv (preprint)

openreview.net

Speed Science

Leading in a New Era

Supervision Requests

Stanislaw Jastrzebski

Publications

Speed Science

Leading in a New Era

Supervision Requests

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Stanislaw Jastrzebski

Publications