The growing volume of omics and clinical data generated for neurodegenerative diseases (NDs) requires new approaches for their curation so they can be ready-to-use in bioinformatics. NeuroEmbed is an approach for the engineering of semantically accurate embedding spaces to represent cohorts and samples. The NeuroEmbed method comprises four stages: (1) extraction of ND cohorts from public repositories; (2) semi-automated normalization and augmentation of metadata of cohorts and samples using biomedical ontologies and clustering on the embedding space; (3) automated generation of a natural language question-answering (QA) dataset for cohorts and samples based on randomized combinations of standardized metadata dimensions and (4) fine-tuning of a domain-specific embedder to optimize queries. We illustrate the approach using the GEO repository and the PubMedBERT pretrained embedder. Applying NeuroEmbed, we semantically indexed 2,801 repositories and 150,924 samples. Amongst many biology-relevant categories, we normalized more than 1,700 heterogeneous tissue labels from GEO into 326 unique ontology-aligned concepts and enriched annotations with new ontology-aligned terms, leading to a fold increase in size for the metadata terms between 2.7 and 20 fold. After fine-tuning PubMedBERT with the QA training data augmented with the enlarged metadata, the model increased its mean Retrieval Precision from 0.277 to 0.866 and its mean Percentile Rank from 0.355 to 0.896. The NeuroEmbed methodology for the creation of electronic catalogues of omics cohorts and samples will foster automated bioinformatic pipelines construction.

Modern Large Language Model (LLM) systems typically rely on Retrieval Augmented Generation (RAG) which aims to gather context that is useful for response generation. These RAG systems typically optimize strictly towards retrieving context that is maximally relevant to the query. However, conventional theory suggests that retrieval systems which seek to maximize context relevance without any additional explicit criteria can create information bottlenecks. We reaffirm this finding in the modern age of LLM's by showing that in standard RAG pipelines, maximizing for context relevance alone can degrade downstream response quality. In response, we show evaluations of existing RAG methods which account for both context relevance and answer quality. These evaluations introduce a novel finding that existing RAG systems scale poorly with inference time compute usage when considering our combined metric. We introduce "RErank BEyond reLevance (REBEL)", which enables RAG systems to scale with inference-time compute via injection of multi-criteria optimization using Chain-of-Thought prompting (and optionally Multi-Turn dialogue). Ultimately, this enables a new performance/speed tradeoff curve, where RAG systems are able to achieve both higher relevance of retrieved contexts and superior answer quality as inference time increases. Code for the implementation of our method in llama-index can be found at the following PR: https://github.com/run-llama/llama_index/pull/17590. Code for running experiments using this llama-index implementation can be found at https://github.com/microsoft/REBEL.

Extracting parameters from technical documentation is crucial for ensuring design precision and simulation reliability in electronic design. However, current methods struggle to handle high-dimensional design data and meet the demands of real-time processing. In electronic design automation (EDA), engineers often manually search through extensive documents to retrieve component parameters required for constructing PySpice models, a process that is both labor-intensive and time-consuming. To address this challenge, we propose an innovative framework that leverages large language models (LLMs) to automate the extraction of parameters and the generation of PySpice models directly from datasheets. Our framework introduces three Chain-of-Thought (CoT) based techniques: (1) Targeted Document Retrieval (TDR), which enables the rapid identification of relevant technical sections; (2) Iterative Retrieval Optimization (IRO), which refines the parameter search through iterative improvements; and (3) Preference Optimization (PO), which dynamically prioritizes key document sections based on relevance. Experimental results show that applying all three methods together improves retrieval precision by 47.69% and reduces processing latency by 37.84%. Furthermore, effect size analysis using Cohen's d reveals that PO significantly reduces latency, while IRO contributes most to precision enhancement. These findings underscore the potential of our framework to streamline EDA processes, enhance design accuracy, and shorten development timelines. Additionally, our algorithm has model-agnostic generalization, meaning it can improve parameter search performance across different LLMs.

Retrieval-Augmented Generation (RAG) is essential for integrating external knowledge into Large Language Model (LLM) outputs. While the literature on RAG is growing, it primarily focuses on systematic reviews and comparisons of new state-of-the-art (SoTA) techniques against their predecessors, with a gap in extensive experimental comparisons. This study begins to address this gap by assessing various RAG methods' impacts on retrieval precision and answer similarity. We found that Hypothetical Document Embedding (HyDE) and LLM reranking significantly enhance retrieval precision. However, Maximal Marginal Relevance (MMR) and Cohere rerank did not exhibit notable advantages over a baseline Naive RAG system, and Multi-query approaches underperformed. Sentence Window Retrieval emerged as the most effective for retrieval precision, despite its variable performance on answer similarity. The study confirms the potential of the Document Summary Index as a competent retrieval approach. All resources related to this research are publicly accessible for further investigation through our GitHub repository ARAGOG (https://github.com/predlico/ARAGOG). We welcome the community to further this exploratory study in RAG systems.

The success of therapeutic antibodies relies on their ability to selectively bind antigens. AI-based antibody design protocols have shown promise in generating epitope-specific designs. Many of these protocols use an inverse folding step to generate diverse sequences given a backbone structure. Due to prohibitive screening costs, it is key to identify candidate sequences likely to bind in vitro. Here, we compare the efficacy of 8 common scoring paradigms based on open-source models to classify antibody designs as binders or non-binders. We evaluate these approaches on a novel surface plasmon resonance (SPR) dataset, spanning 5 antigens. Our results show that existing methods struggle to detect binders, and performance is highly variable across antigens. We find that metrics computed on flexibly docked antibody-antigen complexes are more robust, and ensembles scores are more consistent than individual metrics. We provide experimental insight to analyze current scoring techniques, highlighting that the development of robust, zero-shot filters is an important research gap.

In this paper, we propose a novel hash learning approach that has the following main distinguishing features, when compared to past frameworks. First, the codewords are utilized in the Hamming space as ancillary techniques to accomplish its hash learning task. These codewords, which are inferred from the data, attempt to capture grouping aspects of the data's hash codes. Furthermore, the proposed framework is capable of addressing supervised, unsupervised and, even, semi-supervised hash learning scenarios. Additionally, the framework adopts a regularization term over the codewords, which automatically chooses the codewords for the problem. To efficiently solve the problem, one Block Coordinate Descent algorithm is showcased in the paper. We also show that one step of the algorithms can be casted into several Support Vector Machine problems which enables our algorithms to utilize efficient software package. For the regularization term, a closed form solution of the proximal operator is provided in the paper. A series of comparative experiments focused on content-based image retrieval highlights its performance advantages.

A General Similarity Measurement (GSM), which takes into account of both non-temporal and rich temporal aspects including temporal order, temporal duration and temporal gap, is proposed for state-sequence matching. It is believed to be versatile enough to subsume representative existing measurements as its special cases.

High retrieval precision in content-based image retrieval can be attained by adopting relevance feedback mechanisms. These mechanisms require that the user judges the quality of the results of the query by marking all the retrieved images as being either relevant or not. Then, the search engine exploits this information to adapt the search to better meet user's needs. At present, the vast majority of proposed relevance feedback mechanisms are formulated in terms of search model that has to be optimized. Such an optimization involves the modification of some search parameters so that the nearest neighbor of the query vector contains the largest number of relevant images.

High retrieval precision in content-based image retrieval can be attained by adopting relevance feedback mechanisms. These mechanisms require that the user judges the quality of the results of the query by marking all the retrieved images as being either relevant or not. Then, the search engine exploits this information to adapt the search to better meet user's needs. At present, the vast majority of proposed relevance feedback mechanisms are formulated in terms of search model that has to be optimized. Such an optimization involves the modification of some search parameters so that the nearest neighbor of the query vector contains the largest number of relevant images.

High retrieval precision in content-based image retrieval can be attained by adopting relevance feedback mechanisms. These mechanisms require that the user judges the quality of the results of the query by marking all the retrieved images as being either relevant or not. Then, the search engine exploits this information to adapt the search to better meet user's needs. At present, the vast majority of proposed relevance feedback mechanisms are formulated in terms of search model that has to be optimized. Such an optimization involves the modification of some search parameters so that the nearest neighbor of the query vector contains the largest number of relevant images.