Search bioRxiv⌕ Search

Biology subjects

Naumov, V.

Publications and source records attributed to Naumov, V..

8 recordsLinked to original sources

The End of Aging Clocks: Training Foundation Models to Reason in Aging and Longevity

The aging clock paradigm has yielded dozens of specialist models that can estimate chronological age or mortality from virtually any biodata type. Yet each such model operates within a fixed modality, relies on a predetermined feature set, and produces limited biological interpretation. Here, we report Longevity-LLM v0.1, a Qwen3-14B model fine-tuned through supervised and reinforcement learning regimes on DNA methylation, proteomics, clinical biomarker, and RNA expression data. Longevity-LLM achieves high ranks in the recently announced Longevity Bench, including such tasks as cancer survival and RNA- or proteome-based age prediction. After reinforcement fine-tuning, the model achieved a 4.34-year MAE in epigenetic age prediction, surpassing the Horvath multi-tissue clock. In addition to age prediction, Longevity-LLM can carry out numerous other tasks, including proteomic profile generation, for which it significantly outperforms all frontier LLMs. These results demonstrate that a single modestly sized LLM can match or replace purpose-built aging clocks across data modalities. This work constitutes an interim report from the initial sprint of our Multi-Modal AI Gym for Science (MMAI), an initiative dedicated to building foundation models for drug discovery and aging research.

bioinformatics↗

Longevity Bench: Are SotA LLMs ready for aging research?

Aging is a core biological process observed in most species and tissues, which is studied with a vast array of technologies. We argue that the abilities of AI systems to emulate aging and to accurately interpret biodata in its context are the key criteria to judge an LLMs utility in biomedical research. Here, we present LongevityBench -- a collection of tasks designed to assess whether foundation models grasp the fundamental principles of aging biology and can use low-level biodata to arrive at phenotype-level conclusions. The benchmark covers a variety of prediction targets including human time-to-death, mutations effect on lifespan, and age-dependent omics patterns. It spans all common biodata types used in longevity research: transcriptomes, DNA methylation profiles, proteomes, genomes, clinical blood tests and biometrics, as well as natural language annotations. After ranking state-of-the-art foundation models using LongevityBench, we highlight their weaknesses and outline procedures to maximize their utility in aging research and life sciences.

bioinformatics↗

Advancing Target Discovery Through Disease-Specific Integration of Multi-Modal Target Identification Models and Comprehensive Target Benchmarking System

Target identification is crucial for drug development. AI-driven approaches leveraging multi-omics and computational modeling can accelerate this process. However, integrating multi-modal data for disease-specific target identification and predicting translational potential remains challenging. Moreover, the absence of a systematic evaluation framework for model performance limits confidence in target reliability. We present a unified platform combining machine learning-based target identification with comprehensive benchmarking. As a testbed, we developed Target Identification Pro (TargetPro), a disease-specific model spanning 38 diseases across oncology, metabolic, immune, fibrotic, and neurological categories. TargetPro shows strong predictive performance for clinical-stage targets and reveals disease-specific patterns, underscoring the need for tailored target detection models. We next created Target Identification Benchmark (TargetBench 1.0) to rigorously assess target identification systems, including large language models, based on their ability to recover established targets and find high-quality novel candidates. This integrated approach offers a streamlined strategy to evaluate target discovery models, ultimately improving drug development efficiency.

bioinformatics↗

DORA AI Scientist: Multi-agent Virtual Research Team for Scientific Exploration Discovery and Automated Report Generation

Modern goal-oriented scientific research process involves hierarchical teams of researchers of diverse backgrounds performing generalist and domain-specific tasks. Many of these tasks include hypothesis generation, literature review, data collection, cleanup, processing and analysis, experimental design, virtual and physical experiments, research report and academic paper writing, reference management, bibliography and quality control. Most of these tasks can be performed automatically or in a co-pilot mode by the generative reinforcement learning systems. In this paper, we introduce a versatile multi-agent scientific exploration and draft outline research assistant (DORA), which provides multiple templates and workflows for automated or semi-automated research studies and report generation. Under user guidance, it employs hierarchical teams of AI agents based on the plug-and-play generalist and domain-specific large language models (LLMs) exploiting a variety of specialized research tools and open data repositories and generates high-quality research outputs publication drafts with maximally-accurate references. DORA is designed to minimize the time and effort required for manuscript preparation, thereby enabling researchers to devote more attention to high-value discovery tasks. The system is constantly evolving with user feedback with regular feature and resource updates. The platform is available at https://dora.insilico.com.

bioinformatics↗

Precious3GPT: Multimodal Multi-Species Multi-Omics Multi-Tissue Transformer for Aging Research and Drug Discovery

We present a multimodal multi-species multi-omics multi-tissue transformer for aging research and drug discovery capable of performing multiple tasks such as age prediction across species, target discovery, tissue, sex, and disease sample classification, drug sensitivity prediction, replication of omics response and prediction of biological and phenotypic response to compound treatment. This model combines textual, tabular, and knowledge graph-derived representations of biological experiments to provide insights into molecular-level biological processes. We demonstrate that P3GPT has developed an intuition for the interactions between compounds, pathologies, and gene regulation in the context of multiple species and tissues. In these areas, it outperforms existing LLMs and we highlight its utility in diverse case studies. P3GPT is a general model that may be used as a target identification tool, aging clock, digital laboratory, and scientific assistant. The model is intended as a community resource available open source as well as via a Discord server.

bioinformatics↗

Advanced Cardiovascular Toxicity Screening: Integrating Human iPSC-Derived Cardiomyocytes with In Silico Models

The pharmaceutical industry is evolving with the use of hiPSC-derived cardiomyocytes (hiPSC-CM) for in vitro cardiac safety screening. Traditional reliance on QT interval prolongation as a main cardiotoxicity marker is being challenged. In addition, Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative recommends using computer modeling and in silico platforms as more comprehensive approach for cardiotoxicity testing in conjunction with hiPSC-CM in vitro screening. Our study presents such an innovative platform that integrates in vitro hiPSC-CM propagation test with in silico models to assess cardiotoxicity. Utilizing the electrophysiological and morphological characteristics of hiPSC-CM, we offer a thorough evaluation of potential drug-induced cardiac risks by computer modelling. We show, using the example of lidocaine and other antiarrhythmics, that using a integrative experimental and computer platform, the possibility to correctly display the clinical manifestations of side effects in advance.

pharmacology and toxicology↗

Comparative analysis of novel MGISEQ-2000 sequencing platform vs Illumina HiSeq 2500 for whole-genome sequencing

BackgroundMGISEQ-2000 developed by MGI Tech Co. Ltd. (a subsidiary of the BGI Group) is a new competitor of such next-generation sequencing platforms as NovaSeq and HiSeq (Illumina). Its sequencing principle is based on the DNB and cPAS technologies, which were also used in the previous version of the BGISEQ-500 device. However, the reagents for MGISEQ-2000 have been refined and the platform utilizes updated software. The cPAS method is an advanced technology based on cPAL previously created by Complete Genomics. ResultIn this paper, the authors compare the results of the whole-genome sequencing of a DNA sample from a Russian female donor performed on MGISEQ-2000 and Illumina HiSeq 2500 (both PE150). Two platforms were compared in terms of sequencing quality, number of errors and performance. Additionally, we performed variant calling using four different software packages: Samtools mpileaup, Strelka2, Sentieon, and GATK. The accuracy of single nucleotide polymorphism (SNP) detection was similar in the data generated by MGISEQ-2000 and HiSeq 2500, which was used as a reference. At the same time, a separate indel analysis of the overall error rate revealed similar FPR values and lower sensitivity. Conclusionsit may be concluded with confidence that the data generated by the analyzed sequencing systems is characterized by comparable magnitudes of error and that MGISEQ-2000 can be used for a wide range of research tasks on par with HiSeq 2500.

genomics↗

VolcanoR - web service to produce volcano plots and do basic enrichment analysis

Summary: We introduce VolcanoR - web based tool to analyse results of differential gene expression. It takes a table containing gene name p-value and foldChange as input data. It can produce publication quality volcano plots, apply different p-value and fold change thresholds and do basic GeneOntology and KEGG enrichment analysis with selected gene set. For now it supports H.sapiens, R.norvegicus and M.musclus.\n\nAvailability and Implementation: VolcanoR is wtitten using R Shiny framework. It is publically available at http://volcanor.bioinf.su or stand-alone application, that can be downloaded at https://github.com/vovalive/volcanoR\n\nContact: looongdog@gmail.com

bioinformatics↗