q-bio.QM

arXiv:2501.01458v1 Announce Type: new Abstract: Identifying druggable genes is essential for developing effective pharmaceuticals. With the availability of extensive, high-quality data, computational methods have become a significant asset. Protein Interaction Network (PIN) is valuable but challenging to implement due to its high dimensionality and sparsity. Previous methods relied on indirect integration, leading to resolution loss. This study proposes GAN-TAT, a framework utilizing an advanced graph embedding technology, ImGAGN, to directly integrate PIN for druggable gene inference work. Tested on three Pharos datasets, GAN-TAT achieved the highest AUC-ROC score of 0.951 on Tclin. Further evaluation shows that GAN-TAT's predictions are supported by clinical evidence, highlighting its potential practical applications in pharmacogenomics. This research represents a methodological attempt with the direct utilization of PIN, expanding potential new solutions for developing drug targets. The source code of GAN-TAT is available at (https://github.com/george-yuanji-wang/GAN-TAT).

arXiv:2501.01510v1 Announce Type: new Abstract: Brain age is the estimate of biological age derived from neuroimaging datasets using machine learning algorithms. Increasing \textit{brain age gap} characterized by an elevated brain age relative to the chronological age can reflect increased vulnerability to neurodegeneration and cognitive decline. Hence, brain age gap is a promising biomarker for monitoring brain health. However, black-box machine learning approaches to brain age gap prediction have limited practical utility. Recent studies on coVariance neural networks (VNN) have proposed a relatively transparent deep learning pipeline for neuroimaging data analyses, which possesses two key features: (i) inherent \textit{anatomically interpretablity} of derived biomarkers; and (ii) a methodologically interpretable perspective based on \textit{linkage with eigenvectors of anatomic covariance matrix}. In this paper, we apply the VNN-based approach to study brain age gap using cortical thickness features for various prevalent neurodegenerative conditions. Our results reveal distinct anatomic patterns for brain age gap in Alzheimer's disease, frontotemporal dementia, and atypical Parkinsonian disorders. Furthermore, we demonstrate that the distinct anatomic patterns of brain age gap are linked with the differences in how VNN leverages the eigenspectrum of the anatomic covariance matrix, thus lending explainability to the reported results.

arXiv:2411.01034v2 Announce Type: replace-cross Abstract: Our study introduces ResNet-L2 (RL2), a novel metric for evaluating generative models and image quality in histopathology, addressing limitations of traditional metrics, such as Frechet inception distance (FID), when the data is scarce. RL2 leverages ResNet features with a normalizing flow to calculate RMSE distance in the latent space, providing reliable assessments across diverse histopathology datasets. We evaluated the performance of RL2 on degradation types, such as blur, Gaussian noise, salt-and-pepper noise, and rectangular patches, as well as diffusion processes. RL2's monotonic response to increasing degradation makes it well-suited for models that assess image quality, proving a valuable advancement for evaluating image generation techniques in histopathology. It can also be used to discard low-quality patches while sampling from a whole slide image. It is also significantly lighter and faster compared to traditional metrics and requires fewer images to give stable metric value.

arXiv:2501.00013v1 Announce Type: cross Abstract: Antibodies are Y-shaped proteins that protect the host by binding to specific antigens, and their binding is mainly determined by the Complementary Determining Regions (CDRs) in the antibody. Despite the great progress made in CDR design, existing computational methods still encounter several challenges: 1) poor capability of modeling complex CDRs with long sequences due to insufficient contextual information; 2) conditioned on pre-given antigenic epitopes and their static interaction with the target antibody; 3) neglect of specificity during antibody optimization leads to non-specific antibodies. In this paper, we take into account a variety of node features, edge features, and edge relations to include more contextual and geometric information. We propose a novel Relation-Aware Antibody Design (RAAD) framework, which dynamically models antigen-antibody interactions for co-designing the sequences and structures of antigen-specific CDRs. Furthermore, we propose a new evaluation metric to better measure antibody specificity and develop a contrasting specificity-enhancing constraint to optimize the specificity of antibodies. Extensive experiments have demonstrated the superior capability of RAAD in terms of antibody modeling, generation, and optimization across different CDR types, sequence lengths, pre-training strategies, and input contexts.

arXiv:2401.07126v3 Announce Type: replace-cross Abstract: Quantitative analysis of pseudo-diffusion in diffusion-weighted magnetic resonance imaging (DWI) data shows potential for assessing fetal lung maturation and generating valuable imaging biomarkers. Yet, the clinical utility of DWI data is hindered by unavoidable fetal motion during acquisition. We present IVIM-morph, a self-supervised deep neural network model for motion-corrected quantitative analysis of DWI data using the Intra-voxel Incoherent Motion (IVIM) model. IVIM-morph combines two sub-networks, a registration sub-network, and an IVIM model fitting sub-network, enabling simultaneous estimation of IVIM model parameters and motion. To promote physically plausible image registration, we introduce a biophysically informed loss function that effectively balances registration and model-fitting quality. We validated the efficacy of IVIM-morph by establishing a correlation between the predicted IVIM model parameters of the lung and gestational age (GA) using fetal DWI data of 39 subjects. IVIM-morph exhibited a notably improved correlation with gestational age (GA) when performing in-vivo quantitative analysis of fetal lung DWI data during the canalicular phase. IVIM-morph shows potential in developing valuable biomarkers for non-invasive assessment of fetal lung maturity with DWI data. Moreover, its adaptability opens the door to potential applications in other clinical contexts where motion compensation is essential for quantitative DWI analysis. The IVIM-morph code is readily available at: https://github.com/TechnionComputationalMRILab/qDWI-Morph.

arXiv:2409.19838v2 Announce Type: replace Abstract: Identifying informative low-dimensional features that characterize dynamics in molecular simulations remains a challenge, often requiring extensive manual tuning and system-specific knowledge. Here, we introduce geom2vec, in which pretrained graph neural networks (GNNs) are used as universal geometric featurizers. By pretraining equivariant GNNs on a large dataset of molecular conformations with a self-supervised denoising objective, we obtain transferable structural representations that are useful for learning conformational dynamics without further fine-tuning. We show how the learned GNN representations can capture interpretable relationships between structural units (tokens) by combining them with expressive token mixers. Importantly, decoupling training the GNNs from training for downstream tasks enables analysis of larger molecular graphs (such as small proteins at all-atom resolution) with limited computational resources. In these ways, geom2vec eliminates the need for manual feature selection and increases the robustness of simulation analyses.

arXiv:2207.01586v3 Announce Type: replace-cross Abstract: Accurate prediction of RNA three-dimensional (3D) structure remains an unsolved challenge. Determining RNA 3D structures is crucial for understanding their functions and informing RNA-targeting drug development and synthetic biology design. The structural flexibility of RNA, which leads to scarcity of experimentally determined data, complicates computational prediction efforts. Here, we present RhoFold+, an RNA language model-based deep learning method that accurately predicts 3D structures of single-chain RNAs from sequences. By integrating an RNA language model pre-trained on ~23.7 million RNA sequences and leveraging techniques to address data scarcity, RhoFold+ offers a fully automated end-to-end pipeline for RNA 3D structure prediction. Retrospective evaluations on RNA-Puzzles and CASP15 natural RNA targets demonstrate RhoFold+'s superiority over existing methods, including human expert groups. Its efficacy and generalizability are further validated through cross-family and cross-type assessments, as well as time-censored benchmarks. Additionally, RhoFold+ predicts RNA secondary structures and inter-helical angles, providing empirically verifiable features that broaden its applicability to RNA structure and function studies.

arXiv:2412.13228v2 Announce Type: replace-cross Abstract: Molecular subtyping of cancer is recognized as a critical and challenging upstream task for personalized therapy. Existing deep learning methods have achieved significant performance in this domain when abundant data samples are available. However, the acquisition of densely labeled samples for cancer molecular subtypes remains a significant challenge for conventional data-intensive deep learning approaches. In this work, we focus on the few-shot molecular subtype prediction problem in heterogeneous and small cancer datasets, aiming to enhance precise diagnosis and personalized treatment. We first construct a new few-shot dataset for cancer molecular subtype classification and auxiliary cancer classification, named TCGA Few-Shot, from existing publicly available datasets. To effectively leverage the relevant knowledge from both tasks, we introduce a task-specific embedding-based meta-learning framework (TSEML). TSEML leverages the synergistic strengths of a model-agnostic meta-learning (MAML) approach and a prototypical network (ProtoNet) to capture diverse and fine-grained features. Comparative experiments conducted on the TCGA Few-Shot dataset demonstrate that our TSEML framework achieves superior performance in addressing the problem of few-shot molecular subtype classification.

arXiv:2412.16267v1 Announce Type: new Abstract: Cases of laryngeal cancer are predicted to rise significantly in the coming years. Current diagnostic pathways cause many patients to be incorrectly referred to urgent suspected cancer pathways, putting undue stress on both patients and the medical system. Artificial intelligence offers a promising solution by enabling non-invasive detection of laryngeal cancer from patient speech, which could help prioritise referrals more effectively and reduce inappropriate referrals of non-cancer patients. To realise this potential, open science is crucial. A major barrier in this field is the lack of open-source datasets and reproducible benchmarks, forcing researchers to start from scratch. Our work addresses this challenge by introducing a benchmark suite comprising 36 models trained and evaluated on open-source datasets. These models are accessible in a public repository, providing a foundation for future research. They evaluate three different algorithms and three audio feature sets, offering a comprehensive benchmarking framework. We propose standardised metrics and evaluation methodologies to ensure consistent and comparable results across future studies. The presented models include both audio-only inputs and multimodal inputs that incorporate demographic and symptom data, enabling their application to datasets with diverse patient information. By providing these benchmarks, future researchers can evaluate their datasets, refine the models, and use them as a foundation for more advanced approaches. This work aims to provide a baseline for establishing reproducible benchmarks, enabling researchers to compare new methods against these standards and ultimately advancing the development of AI tools for detecting laryngeal cancer.

arXiv:2412.16220v1 Announce Type: cross Abstract: Inferencing Gene Regulatory Networks (GRNs) from gene expression data is a pivotal challenge in systems biology, and several innovative computational methods have been introduced. However, most of these studies have not considered the skewed degree distribution of genes.Specifically, some genes may regulate multiple target genes while some genes may be regulated by multiple regulator genes.Such a skewed degree distribution issue significantly complicates the application of directed graph embedding methods. To tackle this issue, we propose the Cross-Attention Complex Dual Graph Embedding Model (XATGRN). Our XATGRN employs a cross-attention mechanism to effectively capture intricate gene interactions from gene expression profiles. Additionally, it uses a Dual Complex Graph Embedding approach to manage the skewed degree distribution, thereby ensuring precise prediction of regulatory relationships and their directionality. Our model consistently outperforms existing state-of-the-art methods across various datasets, underscoring its efficacy in elucidating complex gene regulatory mechanisms. Our codes used in this paper are publicly available at: https://github.com/kikixiong/XATGRN.

arXiv:2412.16262v1 Announce Type: cross Abstract: During a virus's evolution,various regions of the genome are subjected to distinct levels of functional constraints.Combined with factors like codon bias and DNA repair efficiency,these constraints contribute to unique mutation patterns within the genome or a specific gene. In this project, we harnessed the power of Large Language Models(LLMs) to predict the evolution of SARS-CoV-2. By treating the mutation process from one generation to the next as a translation task, we trained a transformer model, called VirusT5, to capture the mutation patterns underlying SARS-CoV-2 evolution. We evaluated the VirusT5's ability to detect these mutation patterns including its ability to identify mutation hotspots and explored the potential of using VirusT5 to predict future virus variants. Our findings demonstrate the feasibility of using a large language model to model viral evolution as a translation process. This study establishes the groundbreaking concept of "mutation-as-translation," paving the way for new methodologies and tools for combating virus threats

arXiv:2412.16276v1 Announce Type: cross Abstract: Classifying antimicrobial peptides(AMPs) from the vast array of peptides mined from metagenomic sequencing data is a significant approach to addressing the issue of antibiotic resistance. However, current AMP classification methods, primarily relying on sequence-based data, neglect the spatial structure of peptides, thereby limiting the accurate classification of AMPs. Additionally, the number of known AMPs is significantly lower than that of non-AMPs, leading to imbalanced datasets that reduce predictive accuracy for AMPs. To alleviate these two limitations, we first employ Omegafold to predict the three-dimensional spatial structures of AMPs and non-AMPs, constructing peptide graphs based on the amino acids' C$_\alpha$ positions. Building upon this, we propose a novel classification model named Spatial GNN-based AMP Classifier (SGAC). Our SGAC model employs a graph encoder based on Graph Neural Networks (GNNs) to process peptide graphs, generating high-dimensional representations that capture essential features from the three-dimensional spatial structure of amino acids. Then, to address the inherent imbalanced datasets, SGAC first incorporates Weight-enhanced Contrastive Learning, which clusters similar peptides while ensuring separation between dissimilar ones, using weighted contributions to emphasize AMP-specific features. Furthermore, SGAC employs Weight-enhanced Pseudo-label Distillation to dynamically generate high-confidence pseudo labels for ambiguous peptides, further refining predictions and promoting balanced learning between AMPs and non-AMPs. Experiments on publicly available AMP and non-AMP datasets demonstrate that SGAC significantly outperforms traditional sequence-based methods and achieves state-of-the-art performance among graph-based models, validating its effectiveness in AMP classification.

arXiv:2412.09775v2 Announce Type: replace-cross Abstract: Correlative computational microscopy is accelerating the mapping of dynamic biological systems by integrating morphological and molecular measurements across spatial scales, from organelles to entire organisms. Visualization, measurement, and prediction of interactions among the components of biological systems can be accelerated by generalist computational imaging frameworks that relax the trade-offs imposed by multiplex dynamic imaging. This work reports a generalist framework for wave optical imaging of the architectural order (waveOrder) among biomolecules for encoding and decoding multiple specimen properties from a minimal set of acquired channels, with or without fluorescent labels. waveOrder expresses material properties in terms of elegant physically motivated basis vectors directly interpretable as phase, absorption, birefringence, diattenuation, and fluorophore density; and it expresses image data in terms of directly measurable Stokes parameters. We report a corresponding multi-channel reconstruction algorithm to recover specimen properties in multiple contrast modes. With this framework, we implement multiple 3D computational microscopy methods, including quantitative phase imaging, quantitative label-free imaging with phase and polarization, and fluorescence deconvolution imaging, across scales ranging from organelles to whole zebrafish. These advances are available via an extensible open-source computational imaging library, waveOrder, and a napari plugin, recOrder.

arXiv:2412.15947v1 Announce Type: cross Abstract: Study Objectives: We investigate using Mamba-based deep learning approaches for sleep staging on signals from ANNE One (Sibel Health, Evanston, IL), a minimally intrusive dual-sensor wireless wearable system measuring chest electrocardiography (ECG), triaxial accelerometry, and temperature, as well as finger photoplethysmography (PPG) and temperature. Methods: We obtained wearable sensor recordings from 360 adults undergoing concurrent clinical polysomnography (PSG) at a tertiary care sleep lab. PSG recordings were scored according to AASM criteria. PSG and wearable sensor data were automatically aligned using their ECG channels with manual confirmation by visual inspection. We trained Mamba-based models with both convolutional-recurrent neural network (CRNN) and the recurrent neural network (RNN) architectures on these recordings. Ensembling of model variants with similar architectures was performed. Results: Our best approach, after ensembling, attains a 3-class (wake, NREM, REM) balanced accuracy of 83.50%, F1 score of 84.16%, Cohen's $\kappa$ of 72.68%, and a MCC score of 72.84%; a 4-class (wake, N1/N2, N3, REM) balanced accuracy of 74.64%, F1 score of 74.56%, Cohen's $\kappa$ of 61.63%, and MCC score of 62.04%; a 5-class (wake, N1, N2, N3, REM) balanced accuracy of 64.30%, F1 score of 66.97%, Cohen's $\kappa$ of 53.23%, MCC score of 54.38%. Conclusions: Deep learning models can infer major sleep stages from a wearable system without electroencephalography (EEG) and can be successfully applied to data from adults attending a tertiary care sleep clinic.

arXiv:2302.10634v3 Announce Type: replace Abstract: Three-dimensional transesophageal echocardiography (3DTEE) is the recommended imaging technique for the assessment of mitral valve (MV) morphology and lesions in case of mitral regurgitation (MR) requiring surgical or transcatheter repair. Such assessment is key to thorough intervention planning and to intraprocedural guidance. However, it requires segmentation from 3DTEE images, which is timeconsuming, operator-dependent, and often merely qualitative. In the present work, a novel workflow to quantify the patient-specific MV geometry from 3DTEE is proposed. The developed approach relies on a 3D multi-decoder residual convolutional neural network (CNN) with a U-Net architecture for multi-class segmentation of MV annulus and leaflets. The CNN was trained and tested on a dataset comprising 55 3DTEE examinations of MR-affected patients. After training, the CNN is embedded into a fully automatic, and hence fully repeatable, pipeline that refines the predicted segmentation, detects MV anatomical landmarks and quantifies MV morphology. The trained 3D CNN achieves an average Dice score of $0.82 \pm 0.06$, mean surface distance of $0.43 \pm 0.14$ mm and 95% Hausdorff Distance (HD) of $3.57 \pm 1.56$ mm before segmentation refinement, outperforming a state-of-the-art baseline residual U-Net architecture, and provides an unprecedented multi-class segmentation of the annulus, anterior and posterior leaflet. The automatic 3D linear morphological measurements of the annulus and leaflets, specifically diameters and lengths, exhibit differences of less than 1.45 mm when compared to ground truth values. These measurements also demonstrate strong overall agreement with analyses conducted by semi-automated commercial software. The whole process requires minimal user interaction and requires approximately 15 seconds

arXiv:2408.09048v2 Announce Type: replace-cross Abstract: Messenger RNA (mRNA)-based vaccines are accelerating the discovery of new drugs and revolutionizing the pharmaceutical industry. However, selecting particular mRNA sequences for vaccines and therapeutics from extensive mRNA libraries is costly. Effective mRNA therapeutics require carefully designed sequences with optimized expression levels and stability. This paper proposes a novel contextual language model (LM)-based embedding method: mRNA2vec. In contrast to existing mRNA embedding approaches, our method is based on the self-supervised teacher-student learning framework of data2vec. We jointly use the 5' untranslated region (UTR) and coding sequence (CDS) region as the input sequences. We adapt our LM-based approach specifically to mRNA by 1) considering the importance of location on the mRNA sequence with probabilistic masking, 2) using Minimum Free Energy (MFE) prediction and Secondary Structure (SS) classification as additional pretext tasks. mRNA2vec demonstrates significant improvements in translation efficiency (TE) and expression level (EL) prediction tasks in UTR compared to SOTA methods such as UTR-LM. It also gives a competitive performance in mRNA stability and protein production level tasks in CDS such as CodonBERT.

arXiv:2410.06984v2 Announce Type: replace-cross Abstract: The concept of identifiability describes the possibility of inferring the parameters of a dynamic model by observing its output. It is common and useful to distinguish between structural and practical identifiability. The former property is fully determined by the model equations, while the latter is also influenced by the characteristics of the available experimental data. Structural identifiability can be determined by means of symbolic computations, which may be performed before collecting experimental data, and are hence sometimes called a priori analyses. Practical identifiability is typically assessed numerically, with methods that require simulations - and often also optimization - and are applied a posteriori. An approach to study structural local identifiability is to consider it as a particular case of observability, which is the possibility of inferring the internal state of a system from its output. Thus, both properties can be analysed jointly, by building a generalized observability matrix and computing its rank. The aim of this paper is to investigate to which extent such observability-based methods can also inform about practical aspects related with the experimental setup, which are usually not approached in this way. To this end, we explore a number of possible extensions of the rank tests, and discuss the purposes for which they can be informative as well as others for which they cannot.

arXiv:2412.15790v1 Announce Type: cross Abstract: The integration of multi-omic data is pivotal for understanding complex diseases, but its high dimensionality and noise present significant challenges. Graph Neural Networks (GNNs) offer a robust framework for analyzing large-scale signaling pathways and protein-protein interaction networks, yet they face limitations in expressivity when capturing intricate biological relationships. To address this, we propose Graph Sequence Language Model (GraphSeqLM), a framework that enhances GNNs with biological sequence embeddings generated by Large Language Models (LLMs). These embeddings encode structural and biological properties of DNA, RNA, and proteins, augmenting GNNs with enriched features for analyzing sample-specific multi-omic data. By integrating topological, sequence-derived, and biological information, GraphSeqLM demonstrates superior predictive accuracy and outperforms existing methods, paving the way for more effective multi-omic data integration in precision medicine.