arXiv subjects

Tommi S. Jaakkola

Publications and source records attributed to Tommi S. Jaakkola.

At least 19 recordsLinked to original sources

arXiv2026

PackFlow: Generative Molecular Crystal Structure Prediction via Reinforcement Learning Alignment

Organic molecular crystals underpin technologies ranging from pharmaceuticals to organic electronics, yet predicting solid-state packing of molecules remains challenging because candidate generation is combinatorial and stability is only resolved after costly energy evaluations. Here we introduce PackFlow, a flow matching framework for molecular crystal structure prediction (CSP) that generates heavy-atom crystal proposals by jointly sampling Cartesian coordinates and unit-cell lattice parameters given a molecular graph. This lattice-aware generation interfaces directly with downstream relaxation and lattice-energy ranking, positioning PackFlow as a scalable proposal engine within standard CSP pipelines. To explicitly steer generation toward physically favourable regions, we propose physics alignment, a reinforcement learning post-training stage that uses machine-learned interatomic potential energies and forces as stability proxies. Physics alignment improves physical validity without altering inference-time sampling. We validate PackFlow's performance against heuristic baselines through two distinct evaluations. First, on a broad unseen set of molecular systems, we demonstrate superior candidate generation capability, with proposals exhibiting greater structural similarity to experimental polymorphs. Second, we assess the full end-to-end workflow on two unseen CSP blind-test case studies, including relaxation and lattice-energy analysis. In both settings, PackFlow outperforms heuristics-based methods by concentrating probability mass in low-energy basins, yielding candidates that relax into lower-energy minima and offering a practical route to amortize the relax-and-rank bottleneck.

physics.chem-ph↗

arXiv2024

Improved motif-scaffolding with SE(3) flow matching

Protein design often begins with the knowledge of a desired function from a motif which motif-scaffolding aims to construct a functional protein around. Recently, generative models have achieved breakthrough success in designing scaffolds for a range of motifs. However, generated scaffolds tend to lack structural diversity, which can hinder success in wet-lab validation. In this work, we extend FrameFlow, an SE(3) flow matching model for protein backbone generation, to perform motif-scaffolding with two complementary approaches. The first is motif amortization, in which FrameFlow is trained with the motif as input using a data augmentation strategy. The second is motif guidance, which performs scaffolding using an estimate of the conditional score from FrameFlow without additional training. On a benchmark of 24 biologically meaningful motifs, we show our method achieves 2.5 times more designable and unique motif-scaffolds compared to state-of-the-art. Code: https://github.com/microsoft/protein-frame-flow

q-bio.QM↗

arXiv2024

Structural Constraint Integration in Generative Model for Discovery of Quantum Material Candidates

Billions of organic molecules are known, but only a tiny fraction of the functional inorganic materials have been discovered, a particularly relevant problem to the community searching for new quantum materials. Recent advancements in machine-learning-based generative models, particularly diffusion models, show great promise for generating new, stable materials. However, integrating geometric patterns into materials generation remains a challenge. Here, we introduce Structural Constraint Integration in the GENerative model (SCIGEN). Our approach can modify any trained generative diffusion model by strategic masking of the denoised structure with a diffused constrained structure prior to each diffusion step to steer the generation toward constrained outputs. Furthermore, we mathematically prove that SCIGEN effectively performs conditional sampling from the original distribution, which is crucial for generating stable constrained materials. We generate eight million compounds using Archimedean lattices as prototype constraints, with over 10% surviving a multi-staged stability pre-screening. High-throughput density functional theory (DFT) on 26,000 survived compounds shows that over 50% passed structural optimization at the DFT level. Since the properties of quantum materials are closely related to geometric patterns, our results indicate that SCIGEN provides a general framework for generating quantum materials candidates.

cond-mat.mtrl-sci↗

arXiv2024

Conformal Language Modeling

We propose a novel approach to conformal prediction for generative language models (LMs). Standard conformal prediction produces prediction sets -- in place of single predictions -- that have rigorous, statistical performance guarantees. LM responses are typically sampled from the model's predicted distribution over the large, combinatorial output space of natural language. Translating this process to conformal prediction, we calibrate a stopping rule for sampling different outputs from the LM that get added to a growing set of candidates until we are confident that the output set is sufficient. Since some samples may be low-quality, we also simultaneously calibrate and apply a rejection rule for removing candidates from the output set to reduce noise. Similar to conformal prediction, we prove that the sampled set returned by our procedure contains at least one acceptable answer with high probability, while still being empirically precise (i.e., small) on average. Furthermore, within this set of candidate responses, we show that we can also accurately identify subsets of individual components -- such as phrases or sentences -- that are each independently correct (e.g., that are not "hallucinations"), again with statistical guarantees. We demonstrate the promise of our approach on multiple tasks in open-domain question answering, text summarization, and radiology report generation using different LM variants.

cs.CL↗

arXiv2023

DiffDock-PP: Rigid Protein-Protein Docking with Diffusion Models

Understanding how proteins structurally interact is crucial to modern biology, with applications in drug discovery and protein design. Recent machine learning methods have formulated protein-small molecule docking as a generative problem with significant performance boosts over both traditional and deep learning baselines. In this work, we propose a similar approach for rigid protein-protein docking: DiffDock-PP is a diffusion generative model that learns to translate and rotate unbound protein structures into their bound conformations. We achieve state-of-the-art performance on DIPS with a median C-RMSD of 4.85, outperforming all considered baselines. Additionally, DiffDock-PP is faster than all search-based methods and generates reliable confidence estimates for its predictions. Our code is publicly available at $\texttt{https://github.com/ketatam/DiffDock-PP}$

q-bio.BM↗

arXiv2023

PEOPL: Characterizing Privately Encoded Open Datasets with Public Labels

Allowing organizations to share their data for training of machine learning (ML) models without unintended information leakage is an open problem in practice. A promising technique for this still-open problem is to train models on the encoded data. Our approach, called Privately Encoded Open Datasets with Public Labels (PEOPL), uses a certain class of randomly constructed transforms to encode sensitive data. Organizations publish their randomly encoded data and associated raw labels for ML training, where training is done without knowledge of the encoding realization. We investigate several important aspects of this problem: We introduce information-theoretic scores for privacy and utility, which quantify the average performance of an unfaithful user (e.g., adversary) and a faithful user (e.g., model developer) that have access to the published encoded data. We then theoretically characterize primitives in building families of encoding schemes that motivate the use of random deep neural networks. Empirically, we compare the performance of our randomized encoding scheme and a linear scheme to a suite of computational attacks, and we also show that our scheme achieves competitive prediction accuracy to raw-sample baselines. Moreover, we demonstrate that multiple institutions, using independent random encoders, can collaborate to train improved ML models.

cs.LG↗

arXiv2023

Virtual Node Graph Neural Network for Full Phonon Prediction

The structure-property relationship plays a central role in materials science. Understanding the structure-property relationship in solid-state materials is crucial for structure design with optimized properties. The past few years witnessed remarkable progress in correlating structures with properties in crystalline materials, such as machine learning methods and particularly graph neural networks as a natural representation of crystal structures. However, significant challenges remain, including predicting properties with complex unit cells input and material-dependent, variable-length output. Here we present the virtual node graph neural network to address the challenges. By developing three types of virtual node approaches - the vector, matrix, and momentum-dependent matrix virtual nodes, we achieve direct prediction of $Γ$-phonon spectra and full dispersion only using atomic coordinates as input. We validate the phonon bandstructures on various alloy systems, and further build a $Γ$-phonon database containing over 146,000 materials in the Materials Project. Our work provides an avenue for rapid and high-quality prediction of phonon spectra and bandstructures in complex materials, and enables materials design with superior phonon properties for energy applications. The virtual node augmentation of graph neural networks also sheds light on designing other functional properties with a new level of flexibility.

cond-mat.dis-nn↗

arXiv2022

Fundamental Limits and Tradeoffs in Invariant Representation Learning

A wide range of machine learning applications such as privacy-preserving learning, algorithmic fairness, and domain adaptation/generalization among others, involve learning invariant representations of the data that aim to achieve two competing goals: (a) maximize information or accuracy with respect to a target response, and (b) maximize invariance or independence with respect to a set of protected features (e.g., for fairness, privacy, etc). Despite their wide applicability, theoretical understanding of the optimal tradeoffs -- with respect to accuracy, and invariance -- achievable by invariant representations is still severely lacking. In this paper, we provide an information theoretic analysis of such tradeoffs under both classification and regression settings. More precisely, we provide a geometric characterization of the accuracy and invariance achievable by any representation of the data; we term this feasible region the information plane. We provide an inner bound for this feasible region for the classification case, and an exact characterization for the regression case, which allows us to either bound or exactly characterize the Pareto optimal frontier between accuracy and invariance. Although our contributions are mainly theoretical, a key practical application of our results is in certifying the potential sub-optimality of any given representation learning algorithm for either classification or regression tasks. Our results shed new light on the fundamental interplay between accuracy and invariance, and may be useful in guiding the design of future representation learning algorithms.

cs.LG↗

arXiv2022

Adversarial Support Alignment

We study the problem of aligning the supports of distributions. Compared to the existing work on distribution alignment, support alignment does not require the densities to be matched. We propose symmetric support difference as a divergence measure to quantify the mismatch between supports. We show that select discriminators (e.g. discriminator trained for Jensen-Shannon divergence) are able to map support differences as support differences in their one-dimensional output space. Following this result, our method aligns supports by minimizing a symmetrized relaxed optimal transport cost in the discriminator 1D space via an adversarial process. Furthermore, we show that our approach can be viewed as a limit of existing notions of alignment by increasing transportation assignment tolerance. We quantitatively evaluate the method across domain adaptation tasks with shifts in label distributions. Our experiments show that the proposed method is more robust against these shifts than other alignment-based baselines.

cs.LG↗

arXiv2022

Syfer: Neural Obfuscation for Private Data Release

Balancing privacy and predictive utility remains a central challenge for machine learning in healthcare. In this paper, we develop Syfer, a neural obfuscation method to protect against re-identification attacks. Syfer composes trained layers with random neural networks to encode the original data (e.g. X-rays) while maintaining the ability to predict diagnoses from the encoded data. The randomness in the encoder acts as the private key for the data owner. We quantify privacy as the number of attacker guesses required to re-identify a single image (guesswork). We propose a contrastive learning algorithm to estimate guesswork. We show empirically that differentially private methods, such as DP-Image, obtain privacy at a significant loss of utility. In contrast, Syfer achieves strong privacy while preserving utility. For example, X-ray classifiers built with DP-image, Syfer, and original data achieve average AUCs of 0.53, 0.78, and 0.86, respectively.

cs.LG↗

arXiv2021

Understanding Interlocking Dynamics of Cooperative Rationalization

Selective rationalization explains the prediction of complex neural networks by finding a small subset of the input that is sufficient to predict the neural model output. The selection mechanism is commonly integrated into the model itself by specifying a two-component cascaded system consisting of a rationale generator, which makes a binary selection of the input features (which is the rationale), and a predictor, which predicts the output based only on the selected features. The components are trained jointly to optimize prediction performance. In this paper, we reveal a major problem with such cooperative rationalization paradigm -- model interlocking. Interlocking arises when the predictor overfits to the features selected by the generator thus reinforcing the generator's selection even if the selected rationales are sub-optimal. The fundamental cause of the interlocking problem is that the rationalization objective to be minimized is concave with respect to the generator's selection policy. We propose a new rationalization framework, called A2R, which introduces a third component into the architecture, a predictor driven by soft attention as opposed to selection. The generator now realizes both soft and hard attention over the features and these are fed into the two different predictors. While the generator still seeks to support the original predictor performance, it also minimizes a gap between the two predictors. As we will show theoretically, since the attention-based predictor exhibits a better convexity property, A2R can overcome the concavity barrier. Our experiments on two synthetic benchmarks and two real datasets demonstrate that A2R can significantly alleviate the interlock problem and find explanations that better align with human judgments. We release our code at https://github.com/Gorov/Understanding_Interlocking.

cs.LG↗

arXiv2021

GeoMol: Torsional Geometric Generation of Molecular 3D Conformer Ensembles

Prediction of a molecule's 3D conformer ensemble from the molecular graph holds a key role in areas of cheminformatics and drug discovery. Existing generative models have several drawbacks including lack of modeling important molecular geometry elements (e.g. torsion angles), separate optimization stages prone to error accumulation, and the need for structure fine-tuning based on approximate classical force-fields or computationally expensive methods such as metadynamics with approximate quantum mechanics calculations at each geometry. We propose GeoMol--an end-to-end, non-autoregressive and SE(3)-invariant machine learning approach to generate distributions of low-energy molecular 3D conformers. Leveraging the power of message passing neural networks (MPNNs) to capture local and global graph information, we predict local atomic 3D structures and torsion angles, avoiding unnecessary over-parameterization of the geometric degrees of freedom (e.g. one angle per non-terminal bond). Such local predictions suffice both for the training loss computation, as well as for the full deterministic conformer assembly (at test time). We devise a non-adversarial optimal transport based loss function to promote diverse conformer generation. GeoMol predominantly outperforms popular open-source, commercial, or state-of-the-art machine learning (ML) models, while achieving significant speed-ups. We expect such differentiable 3D structure generators to significantly impact molecular modeling and related applications.

physics.chem-ph↗

arXiv2021

NeuraCrypt: Hiding Private Health Data via Random Neural Networks for Public Training

Balancing the needs of data privacy and predictive utility is a central challenge for machine learning in healthcare. In particular, privacy concerns have led to a dearth of public datasets, complicated the construction of multi-hospital cohorts and limited the utilization of external machine learning resources. To remedy this, new methods are required to enable data owners, such as hospitals, to share their datasets publicly, while preserving both patient privacy and modeling utility. We propose NeuraCrypt, a private encoding scheme based on random deep neural networks. NeuraCrypt encodes raw patient data using a randomly constructed neural network known only to the data-owner, and publishes both the encoded data and associated labels publicly. From a theoretical perspective, we demonstrate that sampling from a sufficiently rich family of encoding functions offers a well-defined and meaningful notion of privacy against a computationally unbounded adversary with full knowledge of the underlying data-distribution. We propose to approximate this family of encoding functions through random deep neural networks. Empirically, we demonstrate the robustness of our encoding to a suite of adversarial attacks and show that NeuraCrypt achieves competitive accuracy to non-private baselines on a variety of x-ray tasks. Moreover, we demonstrate that multiple hospitals, using independent private encoders, can collaborate to train improved x-ray models. Finally, we release a challenge dataset to encourage the development of new attacks on NeuraCrypt.

cs.CR↗

arXiv2020

Unsupervised Hierarchy Matching with Optimal Transport over Hyperbolic Spaces

This paper focuses on the problem of unsupervised alignment of hierarchical data such as ontologies or lexical databases. This is a problem that appears across areas, from natural language processing to bioinformatics, and is typically solved by appeal to outside knowledge bases and label-textual similarity. In contrast, we approach the problem from a purely geometric perspective: given only a vector-space representation of the items in the two hierarchies, we seek to infer correspondences across them. Our work derives from and interweaves hyperbolic-space representations for hierarchical data, on one hand, and unsupervised word-alignment methods, on the other. We first provide a set of negative results showing how and why Euclidean methods fail in this hyperbolic setting. We then propose a novel approach based on optimal transport over hyperbolic spaces, and show that it outperforms standard embedding alignment techniques in various experiments on cross-lingual WordNet alignment and ontology matching tasks.

cs.LG↗

arXiv2020

Oblique Decision Trees from Derivatives of ReLU Networks

We show how neural models can be used to realize piece-wise constant functions such as decision trees. The proposed architecture, which we call locally constant networks, builds on ReLU networks that are piece-wise linear and hence their associated gradients with respect to the inputs are locally constant. We formally establish the equivalence between the classes of locally constant networks and decision trees. Moreover, we highlight several advantageous properties of locally constant networks, including how they realize decision trees with parameter sharing across branching / leaves. Indeed, only $M$ neurons suffice to implicitly model an oblique decision tree with $2^M$ leaf nodes. The neural representation also enables us to adopt many tools developed for deep networks (e.g., DropConnect (Wan et al., 2013)) while implicitly training decision trees. We demonstrate that our method outperforms alternative techniques for training oblique decision trees in the context of molecular property classification and regression tasks.

cs.LG↗

arXiv2020

Invariant Rationalization

Selective rationalization improves neural network interpretability by identifying a small subset of input features -- the rationale -- that best explains or supports the prediction. A typical rationalization criterion, i.e. maximum mutual information (MMI), finds the rationale that maximizes the prediction performance based only on the rationale. However, MMI can be problematic because it picks up spurious correlations between the input features and the output. Instead, we introduce a game-theoretic invariant rationalization criterion where the rationales are constrained to enable the same predictor to be optimal across different environments. We show both theoretically and empirically that the proposed rationales can rule out spurious correlations, generalize better to different test scenarios, and align better with human judgments. Our data and code are available.

cs.LG↗

arXiv2020

Tight Certificates of Adversarial Robustness for Randomly Smoothed Classifiers

Strong theoretical guarantees of robustness can be given for ensembles of classifiers generated by input randomization. Specifically, an $\ell_2$ bounded adversary cannot alter the ensemble prediction generated by an additive isotropic Gaussian noise, where the radius for the adversary depends on both the variance of the distribution as well as the ensemble margin at the point of interest. We build on and considerably expand this work across broad classes of distributions. In particular, we offer adversarial robustness guarantees and associated algorithms for the discrete case where the adversary is $\ell_0$ bounded. Moreover, we exemplify how the guarantees can be tightened with specific assumptions about the function class of the classifier such as a decision tree. We empirically illustrate these results with and without functional restrictions across image and molecule datasets.

cs.LG↗

arXiv2019

Rethinking Cooperative Rationalization: Introspective Extraction and Complement Control

Selective rationalization has become a common mechanism to ensure that predictive models reveal how they use any available features. The selection may be soft or hard, and identifies a subset of input features relevant for prediction. The setup can be viewed as a co-operate game between the selector (aka rationale generator) and the predictor making use of only the selected features. The co-operative setting may, however, be compromised for two reasons. First, the generator typically has no direct access to the outcome it aims to justify, resulting in poor performance. Second, there's typically no control exerted on the information left outside the selection. We revise the overall co-operative framework to address these challenges. We introduce an introspective model which explicitly predicts and incorporates the outcome into the selection process. Moreover, we explicitly control the rationale complement via an adversary so as not to leave any useful information out of the selection. We show that the two complementary mechanisms maintain both high predictive accuracy and lead to comprehensive rationales.

cs.CL↗