Epigenetic aging clocks play a pivotal role in estimating an individual's biological age through the examination of DNA methylation patterns at numerous CpG (Cytosine-phosphate-Guanine) sites within their genome. However, making valid inferences on predicted epigenetic ages, or more broadly, on predictions derived from high-dimensional inputs, presents challenges. We introduce a novel U-learning approach via combinatory multi-subsampling for making ensemble predictions and constructing confidence intervals for predictions of continuous outcomes when traditional asymptotic methods are not applicable. More specifically, our approach conceptualizes the ensemble estimators within the framework of generalized U-statistics and invokes the H\'ajek projection for deriving the variances of predictions and constructing confidence intervals with valid conditional coverage probabilities. We apply our approach to two commonly used predictive algorithms, Lasso and deep neural networks (DNNs), and illustrate the validity of inferences with extensive numerical studies. We have applied these methods to predict the DNA methylation age (DNAmAge) of patients with various health conditions, aiming to accurately characterize the aging process and potentially guide anti-aging interventions.
A specific challenge with deep learning approaches for molecule generation is generating both syntactically valid and chemically plausible molecular string representations. To address this, we propose a novel generative latent-variable transformer model for small molecules that leverages a recently proposed molecular string representation called SAFE. We introduce a modification to SAFE to reduce the number of invalid fragmented molecules generated during training and use this to train our model. Our experiments show that our model can generate novel molecules with a validity rate > 90% and a fragmentation rate < 1% by sampling from a latent space. By fine-tuning the model using reinforcement learning to improve molecular docking, we significantly increase the number of hit candidates for five specific protein targets compared to the pre-trained model, nearly doubling this number for certain targets. Additionally, our top 5% mean docking scores are comparable to the current state-of-the-art (SOTA), and we marginally outperform SOTA on three of the five targets.
In this paper, we consider the physical layer (PHY) security problem for hybrid wiretapping wireless systems in millimeter wave transmission, where active eavesdroppers (AEs) and passive eavesdroppers (PEs) coexist to intercept the confidential messages and emit jamming signals. To achieve secure and reliable transmission, we propose an artificial noise (AN)-aided robust multi-beam array transceiver scheme. Leveraging beamforming, we aim to minimize transmit power by jointly designing the information and AN beamforming, while satisfying valid reception for legitimate users (LUs), per-antenna power constraints for transmitter, as well as all interception power constraints for eavesdroppers (Eves). In particular, the interception power formulation is taken into account for protecting the information against hybrid Eves with imperfect AE channel state information (CSI) and no PE CSI. In light of the intractability of the problem, we reformulate the considered problem by replacing non-convex constraints with tractable forms. Afterwards, a two-stage algorithm is developed to obtain the optimal solution. Additionally, we design the received beamforming weights by means of minimum variance distortionless response, such that the jamming caused by AEs can be effectively suppressed. Simulation results demonstrate the superiority of our proposed scheme in terms of energy efficiency and security.
Important questions for impact evaluation require knowledge not only of average effects, but of the distribution of treatment effects. What proportion of people are harmed? Does a policy help many by a little? Or a few by a lot? The inability to observe individual counterfactuals makes these empirical questions challenging. I propose an approach to inference on points of the distribution of treatment effects by incorporating predicted counterfactuals through covariate adjustment. I show that finite-sample inference is valid under weak assumptions, for example, when data come from a Randomized Controlled Trial (RCT), and that large-sample inference is asymptotically exact under suitable conditions. Finally, I revisit five RCTs in microcredit where average effects are not statistically significant and find evidence of both positive and negative treatment effects in household income. On average across studies, at least 13.6% of households benefited, and 12.5% were negatively affected.
Discovery of novel and promising materials is a critical challenge in the field of chemistry and material science, traditionally approached through methodologies ranging from trial-and-error to machine learning-driven inverse design. Recent studies suggest that transformer-based language models can be utilized as material generative models to expand chemical space and explore materials with desired properties. In this work, we introduce the Catalyst Generative Pretrained Transformer (CatGPT), trained to generate string representations of inorganic catalyst structures from a vast chemical space. CatGPT not only demonstrates high performance in generating valid and accurate catalyst structures but also serves as a foundation model for generating desired types of catalysts by fine-tuning with sparse and specified datasets. As an example, we fine-tuned the pretrained CatGPT using a binary alloy catalyst dataset designed for screening two-electron oxygen reduction reaction (2e-ORR) catalyst and generate catalyst structures specialized for 2e-ORR. Our work demonstrates the potential of language models as generative tools for catalyst discovery.
The key of the text-to-video retrieval (TVR) task lies in learning the unique similarity between each pair of text (consisting of words) and video (consisting of audio and image frames) representations. However, some problems exist in the representation alignment of video and text, such as a text, and further each word, are of different importance for video frames. Besides, audio usually carries additional or critical information for TVR in the case that frames carry little valid information. Therefore, in TVR task, multi-granularity representation of text, including whole sentence and every word, and the modal of audio are salutary which are underutilized in most existing works. To address this, we propose a novel multi-granularity feature interaction module called MGFI, consisting of text-frame and word-frame, for video-text representations alignment. Moreover, we introduce a cross-modal feature interaction module of audio and text called CMFI to solve the problem of insufficient expression of frames in the video. Experiments on benchmark datasets such as MSR-VTT, MSVD, DiDeMo show that the proposed method outperforms the existing state-of-the-art methods.
Latent space Energy-Based Models (EBMs), also known as energy-based priors, have drawn growing interests in the field of generative modeling due to its flexibility in the formulation and strong modeling power of the latent space. However, the common practice of learning latent space EBMs with non-convergent short-run MCMC for prior and posterior sampling is hindering the model from further progress; the degenerate MCMC sampling quality in practice often leads to degraded generation quality and instability in training, especially with highly multi-modal and/or high-dimensional target distributions. To remedy this sampling issue, in this paper we introduce a simple but effective diffusion-based amortization method for long-run MCMC sampling and develop a novel learning algorithm for the latent space EBM based on it. We provide theoretical evidence that the learned amortization of MCMC is a valid long-run MCMC sampler. Experiments on several image modeling benchmark datasets demonstrate the superior performance of our method compared with strong counterparts
Statistical information is ubiquitous but drawing valid conclusions from it is prohibitively hard. We explain how knowledge graph embeddings can be used to approximate probabilistic inference efficiently using the example of Statistical EL (SEL), a statistical extension of the lightweight Description Logic EL. We provide proofs for runtime and soundness guarantees, and empirically evaluate the runtime and approximation quality of our approach.
Petri nets are a promising modeling framework for epidemiology, including the spread of disease across populations or within an individual. In particular, the Susceptible-Infectious-Recovered (SIR) compartment model is foundational for population epidemiological modeling and has been implemented in several prior Petri net studies. However, the SIR model is generally stated as a system of ordinary differential equations (ODEs) with continuous time and variables, while Petri nets are discrete event simulations. To our knowledge, no prior study has investigated the numerical equivalence of Petri net SIR models to the classical ODE formulation. We introduce crucial numerical techniques for implementing SIR models in the GPenSim package for Petri net simulations. We show that these techniques are critical for Petri net SIR models and show a relative root mean squared error of less than 1% compared to ODE simulations for biologically relevant parameter ranges. We conclude that Petri nets provide a valid framework for modeling SIR-type dynamics using biologically relevant parameter values provided that the other PN structures we outline are also implemented.
Interrogation of biological pathways is an integral part of omics data analysis. Large language models (LLMs) enable the generation of custom pathways and gene sets tailored to specific scientific questions. These targeted sets are significantly smaller than traditional pathway enrichment analysis libraries, reducing multiple hypothesis testing and potentially enhancing statistical power. Lomics (Large Language Models for Omics Studies) v1.0 is a python-based bioinformatics toolkit that streamlines the generation of pathways and gene sets for transcriptomic analysis. It operates in three steps: 1) deriving relevant pathways based on the researcher's scientific question, 2) generating valid gene sets for each pathway, and 3) outputting the results as .GMX files. Lomics also provides explanations for pathway selections. Consistency and accuracy are ensured through iterative processes, JSON format validation, and HUGO Gene Nomenclature Committee (HGNC) gene symbol verification. Lomics serves as a foundation for integrating LLMs into omics research, potentially improving the specificity and efficiency of pathway analysis.
Conformal prediction is a powerful framework for constructing prediction sets with valid coverage guarantees in multi-class classification. However, existing methods often rely on a single score function, which can limit their efficiency and informativeness. We propose a novel approach that combines multiple score functions to improve the performance of conformal predictors by identifying optimal weights that minimize prediction set size. Our theoretical analysis establishes a connection between the weighted score functions and subgraph classes of functions studied in Vapnik-Chervonenkis theory, providing a rigorous mathematical basis for understanding the effectiveness of the proposed method. Experiments demonstrate that our approach consistently outperforms single-score conformal predictors while maintaining valid coverage, offering a principled and data-driven way to enhance the efficiency and practicality of conformal prediction in classification tasks.
In this study, we address the issue of API hallucinations in various software engineering contexts. We introduce CloudAPIBench, a new benchmark designed to measure API hallucination occurrences. CloudAPIBench also provides annotations for frequencies of API occurrences in the public domain, allowing us to study API hallucinations at various frequency levels. Our findings reveal that Code LLMs struggle with low frequency APIs: for e.g., GPT-4o achieves only 38.58% valid low frequency API invocations. We demonstrate that Documentation Augmented Generation (DAG) significantly improves performance for low frequency APIs (increase to 47.94% with DAG) but negatively impacts high frequency APIs when using sub-optimal retrievers (a 39.02% absolute drop). To mitigate this, we propose to intelligently trigger DAG where we check against an API index or leverage Code LLMs' confidence scores to retrieve only when needed. We demonstrate that our proposed methods enhance the balance between low and high frequency API performance, resulting in more reliable API invocations (8.20% absolute improvement on CloudAPIBench for GPT-4o).
Instruction-tuned Large Language Models (LLMs) can perform a wide range of tasks given natural language instructions to do so, but they are sensitive to how such instructions are phrased. This issue is especially concerning in healthcare, as clinicians are unlikely to be experienced prompt engineers and the potential consequences of inaccurate outputs are heightened in this domain. This raises a practical question: How robust are instruction-tuned LLMs to natural variations in the instructions provided for clinical NLP tasks? We collect prompts from medical doctors across a range of tasks and quantify the sensitivity of seven LLMs -- some general, others specialized -- to natural (i.e., non-adversarial) instruction phrasings. We find that performance varies substantially across all models, and that -- perhaps surprisingly -- domain-specific models explicitly trained on clinical data are especially brittle, compared to their general domain counterparts. Further, arbitrary phrasing differences can affect fairness, e.g., valid but distinct instructions for mortality prediction yield a range both in overall performance, and in terms of differences between demographic groups.
Generating novel molecules is challenging, with most representations leading to generative models producing many invalid molecules. Spanning Tree-based Graph Generation (STGG) is a promising approach to ensure the generation of valid molecules, outperforming state-of-the-art SMILES and graph diffusion models for unconditional generation. In the real world, we want to be able to generate molecules conditional on one or multiple desired properties rather than unconditionally. Thus, in this work, we extend STGG to multi-property-conditional generation. Our approach, STGG+, incorporates a modern Transformer architecture, random masking of properties during training (enabling conditioning on any subset of properties and classifier-free guidance), an auxiliary property-prediction loss (allowing the model to self-criticize molecules and select the best ones), and other improvements. We show that STGG+ achieves state-of-the-art performance on in-distribution and out-of-distribution conditional generation, and reward maximization.
Conformal prediction (CP) transforms any model's output into prediction sets guaranteed to include (cover) the true label. CP requires exchangeability, a relaxation of the i.i.d. assumption, to obtain a valid distribution-free coverage guarantee. This makes it directly applicable to transductive node-classification. However, conventional CP cannot be applied in inductive settings due to the implicit shift in the (calibration) scores caused by message passing with the new nodes. We fix this issue for both cases of node and edge-exchangeable graphs, recovering the standard coverage guarantee without sacrificing statistical efficiency. We further prove that the guarantee holds independently of the prediction time, e.g. upon arrival of a new node/edge or at any subsequent moment.
Language models (LMs) are often expected to generate strings in some formal language; for example, structured data, API calls, or code snippets. Although LMs can be tuned to improve their adherence to formal syntax, this does not guarantee conformance, especially with smaller LMs suitable for large-scale deployment. In addition, tuning requires significant resources, making it impractical for uncommon or task-specific formats. To prevent downstream parsing errors we would ideally constrain the LM to only produce valid output, but this is severely complicated by tokenization, which is typically both ambiguous and misaligned with the formal grammar. We solve these issues through the application of automata theory, deriving an efficient closed-form solution for the regular languages, a broad class of formal languages with many practical applications, including API calls or schema-guided JSON and YAML. We also discuss pragmatic extensions for coping with the issue of high branching factor, and extend our techniques to deterministic context-free languages, which similarly admit an efficient closed-form solution. Previous work on this topic (Willard and Louf, 2023) layers bespoke solutions onto automata, leading to problems with speed, correctness, and extensibility. Instead, we reformulate the entire task in terms of automata so we can leverage well-studied and well-optimized algorithms. Our system compiles constraints ~7,000x faster, is provably correct, and can be extended in a modular fashion.
We consider the challenging problem of estimating causal effects from purely observational data in the bi-directional Mendelian randomization (MR), where some invalid instruments, as well as unmeasured confounding, usually exist. To address this problem, most existing methods attempt to find proper valid instrumental variables (IVs) for the target causal effect by expert knowledge or by assuming that the causal model is a one-directional MR model. As such, in this paper, we first theoretically investigate the identification of the bi-directional MR from observational data. In particular, we provide necessary and sufficient conditions under which valid IV sets are correctly identified such that the bi-directional MR model is identifiable, including the causal directions of a pair of phenotypes (i.e., the treatment and outcome). Moreover, based on the identification theory, we develop a cluster fusion-like method to discover valid IV sets and estimate the causal effects of interest. We theoretically demonstrate the correctness of the proposed algorithm. Experimental results show the effectiveness of our method for estimating causal effects in bi-directional MR.
There is a growing interest in understanding arguments' strength in Quantitative Bipolar Argumentation Frameworks (QBAFs). Most existing studies focus on attribution-based methods that explain an argument's strength by assigning importance scores to other arguments but fail to explain how to change the current strength to a desired one. To solve this issue, we introduce counterfactual explanations for QBAFs. We discuss problem variants and propose an iterative algorithm named Counterfactual Explanations for Quantitative bipolar Argumentation frameworks (CE-QArg). CE-QArg can identify valid and cost-effective counterfactual explanations based on two core modules, polarity and priority, which help determine the updating direction and magnitude for each argument, respectively. We discuss some formal properties of our counterfactual explanations and empirically evaluate CE-QArg on randomly generated QBAFs.
Dominant dual-encoder models enable efficient image-text retrieval but suffer from limited accuracy while the cross-encoder models offer higher accuracy at the expense of efficiency. Distilling cross-modality matching knowledge from cross-encoder to dual-encoder provides a natural approach to harness their strengths. Thus we investigate the following valuable question: how to make cross-encoder a good teacher for dual-encoder? Our findings are threefold:(1) Cross-modal similarity score distribution of cross-encoder is more concentrated while the result of dual-encoder is nearly normal making vanilla logit distillation less effective. However ranking distillation remains practical as it is not affected by the score distribution.(2) Only the relative order between hard negatives conveys valid knowledge while the order information between easy negatives has little significance.(3) Maintaining the coordination between distillation loss and dual-encoder training loss is beneficial for knowledge transfer. Based on these findings we propose a novel Contrastive Partial Ranking Distillation (CPRD) method which implements the objective of mimicking relative order between hard negative samples with contrastive learning. This approach coordinates with the training of the dual-encoder effectively transferring valid knowledge from the cross-encoder to the dual-encoder. Extensive experiments on image-text retrieval and ranking tasks show that our method surpasses other distillation methods and significantly improves the accuracy of dual-encoder.
Two beam broadening methods for active electronically scanned array (AESA) antennas with uniform amplitude excitation are proposed and compared: phase tapering optimization (PTO) and a novel time-varying phase tapering (TPT). The PTO is a simple and efficient approach assuming continuous polynomial phase distribution and requiring optimization of only few parameters. The TPT is valid mainly for radar applications, taking advantage of the fact that radars typically transmit pulse trains for coherent integration. By varying the array elements' phases from pulse to pulse, the TPT achieves effective amplitude tapering, thus providing a method of beam shaping, occasionally with a simple analytic form. The TPT also makes it possible to produce beam shaping with very low side lobe levels in comparison to the PTO. As a preliminary step, the dimensionality of the radiation pattern characterization for all scan directions is reduced from five to only two variables. This is crucial for efficient optimization of the radiation pattern which needs to be evaluated over a judiciously specified two-dimensional domain.