Generative

This dissertation explores how deep generative models can advance the analysis of challenging biological problems by integrating domain knowledge with deep learning. It focuses on two areas: DNA reaction kinetics and cryogenic electron microscopy (cryo-EM). In the first part, we present ViDa, a biophysics-informed framework leveraging variational autoencoders (VAEs) and geometric scattering transforms to generate biophysically-plausible embeddings of DNA reaction kinetics simulations. These embeddings are reduced to a two-dimensional space to visualize DNA hybridization and toehold-mediated strand displacement reactions. ViDa preserves structure and clusters trajectory ensembles into reaction pathways, making simulation results more interpretable and revealing new mechanistic insights. In the second part, we address key challenges in cryo-EM density map interpretation and protein structure modeling. We provide a comprehensive review and benchmarking of deep learning methods for atomic model building, with improved evaluation metrics and practical guidance. We then present Struc2mapGAN, a generative adversarial network that synthesizes high-fidelity experimental-like cryo-EM density maps from protein structures. Finally, we present CryoSAMU, a structure-aware multimodal U-Net that enhances intermediate-resolution cryo-EM maps by integrating density features with structural embeddings from protein language models via cross-attention. Overall, these contributions demonstrate the potential of deep generative models to interpret DNA reaction mechanisms and advance cryo-EM density map analysis and protein structure modeling.

Generative semantic communication (SemCom) harnesses pretrained generative priors to improve the perceptual quality of wireless image transmission. Existing generative SemCom receivers, however, rely on maximum a posteriori (MAP) estimation, which fundamentally cannot preserve the data distribution and thus limits achievable perceptual quality. Moreover, current diffusion-based approaches using single-domain guidance face significant limitations: latent-domain guidance is sensitive to channel noise, while image-domain guidance inherits decoder bias. Simply combining both domains simultaneously yields an overconfident pseudo-posterior. In this paper, we formulate semantic decoding as a Bayesian inverse problem and prove that posterior sampling achieves optimal perceptual quality by preserving the data distribution. Building on this insight, we propose alternating dual-domain posterior sampling (ADDPS), a diffusion-based SemCom receiver that alternately enforces latent-domain and image-domain consistency during the sampling process. This alternating strategy decomposes joint posterior sampling into simpler subproblems, avoiding gradient conflicts while retaining the complementary strengths of both domains. Experiments on FFHQ demonstrate that the proposed ADDPS achieves superior perceptual quality compared with existing methods.

LLMs are proving to be adept at machine translation although due to their generative nature they may at times overgenerate in various ways. These overgenerations are different from the neurobabble seen in NMT and range from LLM self-explanations, to risky confabulations, to appropriate explanations, where the LLM is able to act as a human translator would, enabling greater comprehension for the target audience. Detecting and determining the exact nature of the overgenerations is a challenging task. We detail different strategies we have explored for our work in a commercial setting, and present our results.

Generative user interfaces (GenUIs) create new opportunities to adapt interfaces to individual users on demand. Yet personalization is difficult because it is not possible to provide settings for screens that have not yet been generated, making it necessary to learn preferences from users' feedback on generated interfaces. Such feedback is sparse, subjective, and often difficult to articulate. We study this problem through a new dataset in which 20 participants each judge the same 600 pairs of GenUIs. Their judgments differ substantially (Krippendorff's alpha = 0.25), and written rationales show that even when participants consider similar UI properties, such as color tone or hierarchy, they often make different choices and prioritize them differently. We develop a sample-efficient personalization method that uses a few pairwise judgments to weight prior users' preferences rather than relying on a fixed rubric of UI attributes. Our method outperforms a pretrained UI evaluator and a larger multimodal model offline. In an online study with 12 new users, participants preferred interfaces personalized by our method over all baselines, including shared guidelines and users' own written preferences.

Accurate longitudinal analysis of brain MRI is often hindered by evolving lesions, which bias automated neuroimaging pipelines. While deep generative models have shown promise in inpainting these lesions, most existing methods operate cross-sectionally or lack 3D anatomical continuity. We present a novel pseudo-3D longitudinal inpainting framework based on Denoising Diffusion Probabilistic Models (DDPM). Our approach utilizes multi-channel conditioning to incorporate longitudinal context from distinct visits (t_1, t_2) and extends Region-Aware Diffusion (RAD) to the medical domain, focusing the generative process on pathological regions without altering surrounding healthy tissue. We evaluated our model against state-of-the-art baselines on longitudinal brain MRI from 93 patients. Our model significantly outperforms the leading baseline (FastSurfer-LIT) in terms of perceptual fidelity, reducing the Learned Perceptual Image Patch Similarity (LPIPS) distance from 0.07 to 0.03 while effectively eliminating inter-slice discontinuities. Furthermore, our model demonstrates high longitudinal stability with a Temporal Fidelity Index of 1.024, closely approaching the ideal value of 1.0 and substantially narrowing the gap compared to LIT's TFI of 1.22. Notably, the RAD mechanism provides a substantial gain in efficiency; our framework achieves an average processing time of 2.53 min per volume, representing approximately 10x speedup over the 24.30 min required by LIT. By leveraging longitudinal priors and region-specific denoising, our framework provides a highly reliable and efficient preprocessing step for the study of progressive neurodegenerative diseases. A derivative dataset consisting of 93 pre-processed scans used for testing will be available upon request after acceptance. Code will be released upon acceptance.

We introduce TerraDiT, a diffusion transformer designed for text-to-satellite image generation with point-based control. Existing controlled satellite image generative models often require pixel-level maps that are time-consuming to acquire, yet semantically limited. To address this limitation, we introduce a novel point-based conditioning framework that controls the generation process through the spatial location of the points and the textual description associated with each point, providing semantically rich control signals. This approach enables flexible, annotation-friendly, and computationally simple inference for satellite image generation. To this end, we introduce an adaptive local attention mechanism that effectively regularizes the attention scores based on the input point queries. We systematically evaluate various domain-specific design choices for training TerraDiT, including the selection of satellite image representation for alignment and geolocation representation for conditioning. Our experiments demonstrate that TerraDiT achieves impressive generation performance, surpassing the state-of-the-art remote sensing generative models. Our models, dataset, and code are available at https://github.com/mvrl/TerraDiT.

We present HairWeaver, a diffusion-based pipeline that animates a single human image with realistic and expressive hair dynamics. While existing methods successfully control body pose, they lack specific control over hair, and as a result, fail to capture the intricate hair motions, resulting in stiff and unrealistic animations. HairWeaver overcomes this limitation using two specialized modules: a Motion-Context-LoRA to integrate motion conditions and a Style-Alignment-LoRA to preserve the subject's photoreal appearance across different data domains. These lightweight components are designed to guide a video diffusion backbone while maintaining its core generative capabilities. By training on a specialized dataset of dynamic human motion generated from a CG simulator, HairWeaver affords fine control over hair motion and ultimately learns to produce highly realistic hair that responds naturally to movement. Comprehensive evaluations demonstrate that our approach sets a new state of the art, producing lifelike human hair animations with dynamic details.

Large language models (LLMs) are widely used as reference-free evaluators via prompting, but this "LLM-as-a-Judge" paradigm is costly, opaque, and sensitive to prompt design. In this work, we investigate whether smaller models can serve as efficient evaluators by leveraging internal representations instead of surface generation. We uncover a consistent empirical pattern: small LMs, despite with weak generative ability, encode rich evaluative signals in their hidden states. This motivates us to propose the Semantic Capacity Asymmetry Hypothesis: evaluation requires significantly less semantic capacity than generation and can be grounded in intermediate representations, suggesting that evaluation does not necessarily need to rely on large-scale generative models but can instead leverage latent features from smaller ones. Our findings motivate a paradigm shift from LLM-as-a-Judge to Representation-as-a-Judge, a decoding-free evaluation strategy that probes internal model structure rather than relying on prompted output. We instantiate this paradigm through INSPECTOR, a probing-based framework that predicts aspect-level evaluation scores from small model representations. Experiments on reasoning benchmarks (GSM8K, MATH, GPQA) show that INSPECTOR substantially outperforms prompting-based small LMs and closely approximates full LLM judges, while offering a more efficient, reliable, and interpretable alternative for scalable evaluation. The code and data are available at: https://github.com/zhuochunli/Representation-as-a-judge

This paper introduces an analytical approach to quantifying and optimizing the distributional discrepancy in generative diffusion models. For a multivariate Gaussian source, we explicitly derive the closed-form evolution trajectory and the resulting Kullback-Leibler (KL) divergence between the distributions of the source data and the reversely sampled data. Asymptotic analysis via the Euler-Maclaurin expansion characterizes the convergence behavior of this KL divergence, extracting its dominant term as an explicit functional of the noise schedule. Minimizing this dominant term via the calculus of variations yields a noise schedule described by a tangent law, inherently determined by the source covariance spectrum. We further prove that the Gaussian source exhibits an extremal property for the KL divergence among general source distributions with a given covariance. We also utilize the analytical KL divergence as a principled metric to identify efficient time discretization strategies for pretrained diffusion models, and demonstrate via experiments over diverse datasets that the identified strategies consistently outperform established baselines, particularly under constrained function evaluation budgets.

Recommendation system delivers substantial economic benefits by providing personalized predictions. Generative recommendation (GR) integrates LLMs to enhance the understanding of long user-item sequences. Despite employing attention-based architectures, GR's workload differs markedly from that of LLM serving. GR typically processes long prompt while producing short, fixed-length outputs, yet the computational cost of each decode phase is especially high due to the large beam width. Furthermore, since the beam search involves a vast item space, the sorting overhead becomes particularly time-consuming. We propose xGR, a GR-oriented serving system that meets strict low-latency requirements under high-concurrency scenarios. First, xGR unifies the processing of prefill and decode phases through staged computation and separated KV cache. Second, xGR enables early sorting termination and mask-based item filtering with data structure reuse. Third, xGR reconstructs the overall pipeline to exploit multi-level overlap and multi-stream parallelism. The experiments on real-world datasets demonstrate that xGR achieves at least 2.89x throughput compared to the state-of-the-art baseline under strict latency constraints.

In web environments, user preferences are often refined progressively as users move from browsing broad categories to exploring specific items. However, existing generative recommenders overlook this natural refinement process. Generative recommendation formulates next-item prediction as autoregressive generation over tokenized user histories, where each item is represented as a sequence of discrete tokens. Prior models typically fuse heterogeneous attributes such as ID, category, title, and description into a single embedding before quantization, which flattens the inherent semantic hierarchy of items and fails to capture the gradual evolution of user intent during web interactions. To address this limitation, we propose CoFiRec, a novel generative recommendation framework that explicitly incorporates the Coarse-to-Fine nature of item semantics into the tokenization process. Instead of compressing all attributes into a single latent space, CoFiRec decomposes item information into multiple semantic levels, ranging from high-level categories to detailed descriptions and collaborative filtering signals. Based on this design, we introduce the CoFiRec Tokenizer, which tokenizes each level independently while preserving structural order. During autoregressive decoding, the language model is instructed to generate item tokens from coarse to fine, progressively modeling user intent from general interests to specific item-level interests. Experiments across multiple public benchmarks and backbones demonstrate that CoFiRec outperforms existing methods, offering a new perspective for generative recommendation. Theoretically, we prove that structured tokenization leads to lower dissimilarity between generated and ground truth items, supporting its effectiveness in generative recommendation. Our code is available at https://github.com/YennNing/CoFiRec.

Generative models, such as large language models or text-to-image diffusion models, can generate relevant responses to user-given queries. Response-based vector embeddings of generative models facilitate statistical analysis and inference on a given collection of black-box generative models. The Data Kernel Perspective Space embedding is one particular method of obtaining response-based vector embeddings for a given set of generative models, already discussed in the literature. In this paper, under appropriate regularity conditions, we establish high probability concentration bounds on the sample vector embeddings for a given set of generative models, obtained through the method of Data Kernel Perspective Space embedding. Our results tell us the required number of sample responses needed in order to approximate the population-level vector embeddings with a desired level of accuracy. The algebraic tools used to establish our results can be used further for establishing concentration bounds on Classical Multidimensional Scaling embeddings in general, when the dissimilarities are observed with noise.

Generative artificial intelligence (GenAI) tools such as OpenAI's ChatGPT are transforming the educational landscape, prompting reconsideration of traditional assessment practices. In parallel, universities are exploring alternatives to in-person, closed-book examinations, raising concerns about academic integrity and pedagogical alignment in uninvigilated settings. This study systematically investigates the performance of GenAI on typical mathematics questions from across a first-year mathematics curriculum. Adopting an empirical approach and utilising current examination questions as a proxy for course content, we generate, transcribe, and blind-mark GenAI submissions to eight undergraduate mathematics assessments, spanning the entirety of the first-year curriculum. By combining independent GenAI responses to individual questions, we enable a meaningful evaluation of GenAI performance, both at the level of modules and across the first-year curriculum. We find that GenAI attainment is at the level of a first-class degree, though current performance can vary between modules. Further, we find that GenAI performance is remarkably consistent when viewed across the entire curriculum, significantly more so than that of students in invigilated examinations. Our findings evidence the pressing need for redesigning assessments in mathematics in the era of generative artificial intelligence.

Text-to-image diffusion models are capable of generating high-quality images, but suboptimal pre-trained text representations often result in these images failing to align closely with the given text prompts. Classifier-free guidance (CFG) is a popular and effective technique for improving text-image alignment in the generative process. However, CFG introduces significant computational overhead. In this paper, we present DIstilling CFG by sharpening text Embeddings (DICE) that replaces CFG in the sampling process with half the computational complexity while maintaining similar generation quality. DICE distills a CFG-based text-to-image diffusion model into a CFG-free version by refining text embeddings to replicate CFG-based directions. In this way, we avoid the computational drawbacks of CFG, enabling high-quality, well-aligned image generation at a fast sampling speed. Furthermore, examining the enhancement pattern, we identify the underlying mechanism of DICE that sharpens specific components of text embeddings to preserve semantic information while enhancing fine-grained details. Extensive experiments on multiple Stable Diffusion v1.5 variants, SDXL, and PixArt-$α$ demonstrate the effectiveness of our method. Code is available at https://github.com/zju-pi/dice.

The design of reinforced concrete (RC) highway barriers is a safety-critical engineering task that requires strict compliance with regulatory provisions such as the AASHTO LRFD Bridge Design Specifications. Current engineering practice relies largely on manual, iterative, and experience-driven procedures to satisfy complex material, geometric, and mechanical constraints. Although standalone large language models (LLMs) show strong capabilities in knowledge representation and text generation, their direct use in structural engineering design is limited by hallucination, numerical reasoning errors, and insufficient integration with physics-based analysis. To address these limitations, this study proposes a "generation-validation-modification" closed-loop framework for automated RC barrier design based on the multi-agent orchestration capability of AutoGen. The framework integrates specialized agents for parameter generation, mechanics-based calculation, target-interval evaluation, deviation diagnosis, and rule-based design modification. The multi-agent framework (MAF) was evaluated on three barrier testing levels (TL-3, TL-4, and TL-5) using sixty RC barrier designs with different geometric configurations. Three DeepSeek models with different parameter scales, DS-8B, DS-32B, and DS-671B, were investigated. All designs were evaluated according to Section 13 of the AASHTO LRFD Bridge Design Specifications, 10th Edition (2024). Results show that MAF-DS-8B achieves a target-interval compliance rate of 98.3%, while the best-performing standalone LLM, DS-32B, achieves 11.7%. These results demonstrate that multi-agent architectures can improve the reliability, interpretability, and accessibility of AI-assisted engineering design for practical applications.

Multi-agent systems composed of large generative models are rapidly moving from laboratory prototypes to real-world deployments, where they jointly plan, negotiate, and allocate shared resources to solve complex tasks. While such systems promise unprecedented scalability and autonomy, their collective interaction also gives rise to failure modes that cannot be reduced to individual agents. Understanding these emergent risks is therefore critical. Here, we present a pioneer study of such emergent multi-agent risk in workflows that involve competition over shared resources (e.g., computing resources or market share), sequential handoff collaboration (where downstream agents see only predecessor outputs), collective decision aggregation, and others. Across these settings, we observe that such group behaviors arise frequently across repeated trials and a wide range of interaction conditions, rather than as rare or pathological cases. In particular, phenomena such as collusion-like coordination and conformity emerge with non-trivial frequency under realistic resource constraints, communication protocols, and role assignments, mirroring well-known pathologies in human societies despite no explicit instruction. Moreover, these risks cannot be prevented by existing agent-level safeguards alone. These findings expose the dark side of intelligent multi-agent systems: a social intelligence risk where agent collectives, despite no instruction to do so, spontaneously reproduce familiar failure patterns from human societies.

Music recordings often suffer from audio quality issues such as excessive reverberation, distortion, clipping, tonal imbalances, and a narrowed stereo image, especially when created in non-professional settings without specialized equipment or expertise. These problems are typically corrected using separate specialized tools and manual adjustments. In this paper, we introduce SonicMaster, the first unified generative model for music restoration and mastering that addresses a broad spectrum of audio artifacts with text-based control. SonicMaster is conditioned on natural language instructions to apply targeted enhancements, or can operate in an automatic mode for general restoration. To train this model, we construct the SonicMaster dataset, a large dataset of paired degraded and high-quality tracks by simulating common degradation types with nineteen degradation functions belonging to five enhancements groups: equalization, dynamics, reverb, amplitude, and stereo. Our approach leverages a flow-matching generative training paradigm to learn an audio transformation that maps degraded inputs to their cleaned, mastered versions guided by text prompts. Objective audio quality metrics demonstrate that SonicMaster significantly improves sound quality across all artifact categories. Furthermore, subjective listening tests confirm that listeners prefer SonicMaster's enhanced outputs over other baselines.

Reconstructing 3D geometry from 2D engineering line drawings is an inherently ambiguous problem: while visible strokes determine the object's projected structure, they do not specify the depth of each stroke. Rather than treating this problem as sketch-based asset generation, where models often infer unobserved structure, we study projection-faithful wireframe reconstruction: lifting a user-provided drawing into 3D according to its visible strokes. We formulate this task as conditional depth estimation over line drawings, predicting a depth value for each drawn pixel to produce a 3D wireframe. To model the ambiguities of orthographic projection, we implement a Latent Diffusion Model with spatial conditioning on the input sketch and optional partial-depth conditioning for iterative reconstruction. We train and evaluate our models on over three million synthetic image-depth pairs derived from CAD wireframes, including a newly curated corpus of roughly 90,000 shapes. Across varying shape complexities, our framework achieves robust reconstruction performance; scaling from 256 to 512 resolution with a retrained latent space roughly halves reconstruction error, reaching a 3.9% best-of-five (7.0% average) normalized depth error. These results demonstrate the potential of projection-faithful depth estimation as a user-controlled approach for iterative 3D wireframe creation in engineering design.

Generative medical event models use tokenized sequences of patient timelines as input, but practical guidance on the many decisions around tokenization is limited. We benchmark quantization granularity, reference-range anchoring, code--value fusion, numeric and temporal encodings, and native versus harmonized event representations from an expert-mapped common data model. Using both Llama and Qwen architectures, 156 models were trained from three initialization seeds, with each configuration following a shared training recipe for up to five epochs. We evaluated learned representations from the first 24 hours of hospitalization with linear probes to predict binary and continuous outcomes during hours 24-48. Fused tokens pairing codes with value deciles increased performance across all eight outcome families relative to the equivalent unfused tokenized input with area under the receiver operating characteristic curve (AUROC) gains of $+0.002$ to $+0.033$ and Spearman correlation gains of $+0.025$ to $+0.114$. Neither anchoring value bins to reference ranges nor increasing quantization granularity consistently improved performance, while xVal variants underperformed both discrete and soft encodings. Alternatives to explicit time tokens, such as event-order and admission-relative rotary position embeddings (RoPE), yielded higher family-mean point estimates across all eight families while reducing input length. When evaluating native input against input mapped to the Common Longitudinal Intensive Care Unit Data Format (CLIF), the CLIF pipeline used 30.8% as many training tokens while improving performance in six of eight outcome families. These findings show tokenization and event encoding are consequential design choices when learning patient representations for downstream classification and regression.