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Oct 30

PepTune: De Novo Generation of Therapeutic Peptides with Multi-Objective-Guided Discrete Diffusion

Peptide therapeutics, a major class of medicines, have achieved remarkable success across diseases such as diabetes and cancer, with landmark examples such as GLP-1 receptor agonists revolutionizing the treatment of type-2 diabetes and obesity. Despite their success, designing peptides that satisfy multiple conflicting objectives, such as target binding affinity, solubility, and membrane permeability, remains a major challenge. Classical drug development and structure-based design are ineffective for such tasks, as they fail to optimize global functional properties critical for therapeutic efficacy. Existing generative frameworks are largely limited to continuous spaces, unconditioned outputs, or single-objective guidance, making them unsuitable for discrete sequence optimization across multiple properties. To address this, we present PepTune, a multi-objective discrete diffusion model for the simultaneous generation and optimization of therapeutic peptide SMILES. Built on the Masked Discrete Language Model (MDLM) framework, PepTune ensures valid peptide structures with state-dependent masking schedules and penalty-based objectives. To guide the diffusion process, we propose a Monte Carlo Tree Search (MCTS)-based strategy that balances exploration and exploitation to iteratively refine Pareto-optimal sequences. MCTS integrates classifier-based rewards with search-tree expansion, overcoming gradient estimation challenges and data sparsity inherent to discrete spaces. Using PepTune, we generate diverse, chemically-modified peptides optimized for multiple therapeutic properties, including target binding affinity, membrane permeability, solubility, hemolysis, and non-fouling characteristics on various disease-relevant targets. In total, our results demonstrate that MCTS-guided discrete diffusion is a powerful and modular approach for multi-objective sequence design in discrete state spaces.

  • 3 authors
·
Dec 23, 2024 2

Google Landmarks Dataset v2 -- A Large-Scale Benchmark for Instance-Level Recognition and Retrieval

While image retrieval and instance recognition techniques are progressing rapidly, there is a need for challenging datasets to accurately measure their performance -- while posing novel challenges that are relevant for practical applications. We introduce the Google Landmarks Dataset v2 (GLDv2), a new benchmark for large-scale, fine-grained instance recognition and image retrieval in the domain of human-made and natural landmarks. GLDv2 is the largest such dataset to date by a large margin, including over 5M images and 200k distinct instance labels. Its test set consists of 118k images with ground truth annotations for both the retrieval and recognition tasks. The ground truth construction involved over 800 hours of human annotator work. Our new dataset has several challenging properties inspired by real world applications that previous datasets did not consider: An extremely long-tailed class distribution, a large fraction of out-of-domain test photos and large intra-class variability. The dataset is sourced from Wikimedia Commons, the world's largest crowdsourced collection of landmark photos. We provide baseline results for both recognition and retrieval tasks based on state-of-the-art methods as well as competitive results from a public challenge. We further demonstrate the suitability of the dataset for transfer learning by showing that image embeddings trained on it achieve competitive retrieval performance on independent datasets. The dataset images, ground-truth and metric scoring code are available at https://github.com/cvdfoundation/google-landmark.

  • 4 authors
·
Apr 3, 2020

Landmarks and Regions: A Robust Approach to Data Extraction

We propose a new approach to extracting data items or field values from semi-structured documents. Examples of such problems include extracting passenger name, departure time and departure airport from a travel itinerary, or extracting price of an item from a purchase receipt. Traditional approaches to data extraction use machine learning or program synthesis to process the whole document to extract the desired fields. Such approaches are not robust to format changes in the document, and the extraction process typically fails even if changes are made to parts of the document that are unrelated to the desired fields of interest. We propose a new approach to data extraction based on the concepts of landmarks and regions. Humans routinely use landmarks in manual processing of documents to zoom in and focus their attention on small regions of interest in the document. Inspired by this human intuition, we use the notion of landmarks in program synthesis to automatically synthesize extraction programs that first extract a small region of interest, and then automatically extract the desired value from the region in a subsequent step. We have implemented our landmark-based extraction approach in a tool LRSyn, and show extensive evaluation on documents in HTML as well as scanned images of invoices and receipts. Our results show that our approach is robust to various types of format changes that routinely happen in real-world settings.

  • 7 authors
·
Apr 11, 2022

Identity-Preserving Talking Face Generation with Landmark and Appearance Priors

Generating talking face videos from audio attracts lots of research interest. A few person-specific methods can generate vivid videos but require the target speaker's videos for training or fine-tuning. Existing person-generic methods have difficulty in generating realistic and lip-synced videos while preserving identity information. To tackle this problem, we propose a two-stage framework consisting of audio-to-landmark generation and landmark-to-video rendering procedures. First, we devise a novel Transformer-based landmark generator to infer lip and jaw landmarks from the audio. Prior landmark characteristics of the speaker's face are employed to make the generated landmarks coincide with the facial outline of the speaker. Then, a video rendering model is built to translate the generated landmarks into face images. During this stage, prior appearance information is extracted from the lower-half occluded target face and static reference images, which helps generate realistic and identity-preserving visual content. For effectively exploring the prior information of static reference images, we align static reference images with the target face's pose and expression based on motion fields. Moreover, auditory features are reused to guarantee that the generated face images are well synchronized with the audio. Extensive experiments demonstrate that our method can produce more realistic, lip-synced, and identity-preserving videos than existing person-generic talking face generation methods.

  • 7 authors
·
May 14, 2023