Biology subjects

Gao, Y.

Publications and source records attributed to Gao, Y..

At least 163 records · Page 9Linked to original sources

bioRxiv2025

Genomic Evidence for Males of Exceptional Reproductive Output (ERO) in Apes and Humans

It is widely suspected that a small percentage of males have exceptional reproductive output (ERO) but progeny numbers of males are rarely measurable, even in humans. If we define the variance ratio of reproductive-output in males and females as = VM/VF, the ERO hypothesis would predict >>1. Since autosomal, X, and Y chromosomes are found in males 1/2, 1/3, and 100% of the time, their DNA diversities can inform about . For example, autosomal and Y-linked diversities are governed, respectively, by (VM+VF)/2 and VM. When comparing the chromosomal diversities, appears to be near 20 for chimpanzees and orangutans, and 1-10 for gorillas. The exception is bonobos with < 1. In humans, the extensive genomic data are coupled to a theory, developed herein, that can filter out selection influences on Y-linked diversities. Hence, the estimation of is rigorous, yielding values near or above 20, depending on the population. When >10, the presence of ERO males is very likely. These analyses can be applied more generally to species with XY sex determination.

evolutionary biology↗

bioRxiv2025

Structural insights into type I and type II Lamassu anti-phage systems

Bacteria have developed a variety of immune systems to combat phage infections. The Lamassu system is a prokaryotic immune system with a core conserved Structural Maintenance of Chromosomes (SMC) superfamily protein LmuB and diverse effectors named LmuA, whose mechanism remains unclear. Here, we present a series of cryo-electron microscopy structures of type I Lamassu complex from Bacillus cellulasensis and type II Lamassu complex from Vibrio cholerae, both in apo- and dsDNA-bound states, which reveal an unexpected stoichiometry and topological architecture, distinct from canonical SMC complexes. Combined structural and biochemical analyses show how the nuclease effector LmuA is sequestered in an inactive monomeric form within the Lamassu complex, and upon sensing foreign DNA ends, dissociates and assembles into an active tetramer capable of DNA cleavage. Our findings elucidate the mechanism by which Lamassu systems detect viral replication and implement anti-phage defense, highlighting the unprecedented roles of SMC proteins in prokaryotic immunity.

microbiology↗

bioRxiv2025

QCatch: A framework for quality control assessment and analysis of single-cell sequencing data

MotivationSingle-cell sequencing data analysis requires robust quality control (QC) to mitigate technical artifacts and ensure reliable downstream results. While tools like alevin-fry and simpleaf (and augmented execution context for the alevin-fry), offer flexibility and computational efficiency to process single-cell data, this ecosystem will further benefit from a standardized QC reporting tailored for its outputs. ResultsWe introduce QCatch, a Python-based command-line tool that generates comprehensive and interactive HTML QC reports designed specifically for single-cell quantification results. Taking the output directory of alevin-fry or simpleaf as the input, QCatch is able to perform essential processing steps, like cell calling, and generate detailed QC reports that contain informative visualizations and statistics, including unique molecular identifier (UMI) count distributions, sequencing saturation estimates, and splicing status information, for QC assurance. Built for seamless integration into downstream analysis workflows, QCatch exports the processed results in a richly-annotated H5AD format file, a widely used data format common among many downstream single-cell data analysis tools. AvailabilityThe source code and documentation of QCatch are available on GitHub at https://github.com/COMBINE-lab/QCatch. QCatch can be installed via both Bioconda and PyPI.

bioinformatics↗

bioRxiv2025

Inferring fitness seascapes from evolutionary histories

Evolutionary dynamics are often conceptualized as walks on an adaptive landscape, with populations climbing toward optimal fitness peaks. However, environmental changes can transform static landscapes into dynamic "fitness seascapes" where natural selection fluctuates in time. Here, we used a path integral approach derived from statistical physics to reveal time-varying selection pressures from genetic sequence data. We found that constraints on the fitness seascape are determined by the screened Poisson equation, which also describes the screening of electric fields in media with mobile charge carriers. In our model, changes in mutation frequencies act as "charges" that reveal the underlying fitness seascape, which is analogous to an electrostatic potential. After validating our method in simulations, we applied it to study how HIV-1 evolves to escape immune control by T cells within individual hosts. Our analysis showed that the fitness benefit of immune escape declines as T cell responses approach their peak intensity, suggesting that functional exhaustion may impair the effectiveness of the immune response against HIV-1. Overall, our approach provides a general framework for capturing the complex dynamics of natural selection in rapidly evolving populations.

evolutionary biology↗

bioRxiv2025

Analysis of Post-Translational Modifications in the Urinary Proteome of Stroke-Prone Spontaneously Hypertensive Rats (SHRSP)

Hypertension, one of the most prevalent chronic non-communicable diseases worldwide, is a primary risk factor for stroke and coronary heart disease. This study investigated dynamic changes in protein post-translational modifications (PTMs) and associated biological processes during hypertension progression by comparing urinary proteome PTMs between stroke-prone spontaneously hypertensive rats (SHRSP) and normal rats at 1-, 8-, and 14-15-month-old stages. Results revealed both stage-specific and shared PTM alterations across hypertensive phases. Notably, multiple differentially modified proteins identified here have been previously implicated in hypertension pathogenesis or progression. Randomized group validation demonstrated that more than 95% of differential modifications between the hypertensive and control groups exhibited non-random characteristics. Furthermore, proteins harboring differential PTMs were significantly enriched in hypertension-related biological pathways and KEGG pathways, including regulation of systemic arterial blood pressure, renin-angiotensin system (RAS), and complement and coagulation cascades. These results highlight distinct urinary proteome PTM profiles between SHRSP and normal rats, providing new insights into the mechanisms of hypertension.

biochemistry↗

bioRxiv2025

Site-Specific Immune and Stromal Architecture Drive Resistance to Trastuzumab Deruxtecan in HER2+ Metastatic Breast Cancer

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) that has demonstrated remarkable efficacy in HER2+ and HER2-low metastatic breast cancer (mBC). Yet, 40-50% of patients fail to respond, and mechanisms underlying resistance, particularly those involving the immune microenvironment, remain poorly understood. To address this gap, we conducted spatial proteomic profiling of metastatic lesions from 25 HER2+ mBC patients treated with T-DXd, using the Bruker GeoMX Digital Spatial Profiler (DSP) platform. Regions of interest (ROIs) were segmented by CD45 expression to distinguish immune-rich versus immune-poor compartments, and spatial marker expression was compared between responders (R) and non-responders (NR). Spearman correlation analysis was used to assess spatial coordination among HER2, fibronectin, and immune markers. Non-responders exhibited greater HER2 heterogeneity, lower CD45+ immune infiltration, and consistent upregulation of fibronectin and granzyme B. In both bone and brain metastases, NR tissues showed strong correlations between fibronectin and T cell markers, indicating spatial immune exclusion. In contrast, NR lymph node metastases displayed negative correlations between fibronectin and immune markers and uncoordinated B-T cell clustering, suggesting an alternative resistance mechanism rooted in immune disorganization rather than exclusion. Collectively, these results implicate HER2 heterogeneity, fibrotic immune exclusion, and immune suppression as key drivers of T-DXd resistance across metastatic sites. By integrating spatial proteomics with clinical outcomes, this study provides novel insights into the spatial immune landscape of ADC resistance and identifies actionable biomarkers for patient stratification and combination therapy design, laying a critical foundation for developing biomarker-guided therapies and personalized treatment strategies to overcome ADC resistance in metastatic breast cancer. Translational SignificanceT-DXd represents a major advance in antibody-drug conjugate (ADC) therapies to address HER2 heterogeneity in tumors through bystander killing. However, treatment options following resistance to T-DXd remain limited, leaving a critical unmet need. As new ADCs continue to emerge, resistance will likely remain a persistent challenge across tumor types. This work extends beyond T-DXd resistance--it provides a framework to address resistance mechanisms common to other ADCs. By investigating immune-mediated mechanisms of ADC resistance, this research identifies therapeutic targets that can be leveraged to develop new treatment strategies. By integrating spatial biology with clinical data, this study offers unprecedented insights into immune-tumor interactions within the resistant tumor microenvironment. This approach deepens mechanistic understanding and enables personalized treatment strategies guided by spatially resolved biomarkers. This novel combination of spatial mechanistic research with clinical data represents advancement toward overcoming ADC resistance and improving outcomes for patients with few therapeutic options.

cancer biology↗

bioRxiv2025

FSCN1-Mediated Hepatic Gluconeogenesis Is Indispensable for Neonatal Mice Survival

Actin-Bundling Protein Fascin1 (FSCN1) is encoded by the Fscn1 gene, and crucial for cytoskeletal remodeling and cellular migration. While previous study linked Fscn1 deficiency to neonatal lethality in mice, the underlying metabolic mechanism remains unexplored. Here, in this study, we report that systemic knockout (KO) of Fscn1 leads to 52.2% mortality within 24 hours post-birth, accompanied by severe hypoglycemia in KO pups compared to other littermates. Remarkably, this lethality was fully rescued by oral glucose administration, indicating a glucose supply-dependent survival mechanism. Surviving Fscn1 KO neonates displayed persistent developmental deficits, including growth retardation and depleted lipid stores, despite intact canonical insulin-regulated hepatic gluconeogenic pathways. Transcriptomic profiling of P0 livers revealed that Fscn1 loss predominantly disrupts metabolic pathway, within the glycerol phosphate shuttle being the most significantly downregulated module. Mechanistically, Fscn1 KO livers exhibited markedly reduced protein levels of glycerol-3-phosphate dehydrogenase isoforms (GPD1/GPD2), key enzymes bridging glycolysis and gluconeogenesis. Consistently, glycerol tolerance tests (GTT) demonstrated impaired glycerol-to-glucose conversion in Fscn1 KO mice, confirming defective glycerol-driven gluconeogenesis. Our findings establish FSCN1 as a novel cytoskeletal-metabolic integrator essential for neonatal survival by sustaining hepatic glucose production from glycerol, thus revealing an unexpected role of actin dynamics in coordinating metabolic adaptation during early postnatal development. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=184 HEIGHT=200 SRC="FIGDIR/small/654691v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@b4fb56org.highwire.dtl.DTLVardef@1e0f47forg.highwire.dtl.DTLVardef@1d3cb1eorg.highwire.dtl.DTLVardef@1bc6022_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIFSCN1 deficiency triggers hypoglycemia-driven neonatal mortality by disrupting hepatic glucose production. C_LIO_LIFscn1 loss impairs the gluconeogenesis via suppressing GPD1/GPD2 expression, while sparing insulin-regulated gluconeogenesis. C_LIO_LICytoskeletal dysfunction impairs glycerol-to-glucose conversion, revealing actin-metabolism crosstalk in postnatal adaptation. C_LI

molecular biology↗

bioRxiv2025

BrainVAE: Exploring the role of white matter BOLD in preclinical Alzheimer disease classification

INTRODUCTIONLike gray matter (GM), white matter (WM) BOLD functional signals change in preclinical AD. However, the potential of WM BOLD for identifying preclinical AD remains underexplored. METHODSWe developed BrainVAE, a transformer-based variational autoencoder with interpretability, to classify preclinical AD and normal controls using resting-state fMRI data. We benchmarked BrainVAE against nine alternative models under three input configurations: WM-only, GM-only, and combined WM+GM. Interpretability analysis was also performed to investigate each brain regions contribution to the classification task. RESULTSBrainVAE outperformed other models and performed well (accuracy = 83.42%, F1-score = 91.62%, AUC = 64.50%) using the combined input compared to WM-only and GM-only. Specific WM bundles--including corpus callosum, fornix, and corticospinal tract--were among the most influential features contributing to the classification. DISCUSSIONIncorporating WM BOLD signals improves the distinction of preclinical AD from controls, underscoring the potential role of WM BOLD features for detecting early-stage AD. HighlightsO_LIBrainVAE integrates white and gray matter BOLD signals for classification of pre-AD and controls. C_LIO_LIBrainVAE achieves high accuracy (83.42%) and F1-score (91.62%) in identifying pre-AD. C_LIO_LIModels using combined WM+GM inputs outperform those using WM-only or GM-only inputs. C_LIO_LIWM regions, such as corpus callosum and fornix, contribute significantly to model predictions. C_LIO_LIResults suggest WM BOLD signals are informative markers for early AD detection. C_LI

neuroscience↗

bioRxiv2025

The Mycobacterium tuberculosis ESX effector promotes pyroptosis-dependent pathogenicity and dissemination

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/653593v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@8cd5e5org.highwire.dtl.DTLVardef@2ec22forg.highwire.dtl.DTLVardef@1ceb773org.highwire.dtl.DTLVardef@6dfba4_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphic AbstractC_FLOATNO C_FIG Mycobacterium tuberculosis (Mtb) remains a major global health threat, partly due to the extensive cytotoxicity induced during infection. Although GSDMD-mediated excessive pyroptosis promotes pathogen dissemination and tissue damage in tuberculosis, the mechanism remains poorly understood. Here, we identify the effector EccB5, a component of the Mtb ESX-5 secretion system, as a key driver of pyroptosis and hyperinflammatory responses. EccB5 enhances Mtb virulence by inducing pyroptosis of macrophages, promoting bacterial dissemination and exacerbating lung pathology. Conditional knockdown EccB5 increases host cell viability. Mechanistically, EccB5 directly interacts with GSDMD, strengthens its association with caspase-1, and facilitates caspase-1-mediated cleavage of GSDMD both in vitro and in vivo. In summary, our findings uncover a precise mechanism by which Mtb modulates host responses and advances its pathogenicity.

microbiology↗

bioRxiv2025

Computational Assessment of Circularization Impact on Saxitoxin G-quadruplex Aptamer Performance

Although high-affinity and high-specificity aptamers can be obtained by SELEX (Systematic Evolution of Ligands by Exponential Enrichment), and have good activity in vitro, their performance in vivo is poor. This is mainly because of the degradation of linear nucleic acids by nucleases in body fluids and the difficulty of maintaining stable 3D structures in complex body fluid environments, which seriously hinders the clinical application of aptamers. This makes circular aptamers, which can resist degradation and are more stable in complex body fluid environments, an attractive option. However, the cyclization process may have a considerable impact on the structure of the original linear aptamer, and blind cyclization may lead to a decrease in its affinity. Here, we developed a new method to guide the cyclization of saxitoxin (STX) aptamers based on molecular computation, and verified the activity of circular aptamers through bioactivity experiments to further verify the authenticity and reliability of our methods. Consistent with the computational analysis, although circularization disrupts the G4 structure, circular aptamer not only has a higher affinity than the linear one but also provides certain protection to mice and greatly prolongs their survival, which proves the accuracy and reliability of the circular structure designed by our computational method. Our findings provide important ideas for better guidance in the design of circular aptamers and demonstrate their great potential in therapeutic applications.

biochemistry↗

bioRxiv2025

Genetic architecture and cellular basis of flag leaf size variation in barley

Flag leaf is the major contributor of photosynthetic assimilates to developing grains. We investigated the genetic architecture and cellular basis of flag leaf length (FLL) and width (FLW) in a multi-parent population comprised of 45 recombinant inbred line (RIL) populations (HvDRR) in barley. Fine mapping of a major quantitative trait locus (QTL) was performed as a first step to isolate the causal gene. Natural variation of FLL and FLW across multi-environment was highly heritable and genotypes adapted to warm climate produced longer and wider flag leaf than those adapted to cooler regions. The variation in flag leaf size was quantitatively inherited and influenced by 24 consensus QTLs of which 17 have not been reported earlier. Further, validation of QTL qHvDRR-FLS-8 and qHvDRR-FLS-17 in nearly isogenic RILs demonstrated that these QTLs also controlled length and width of leaves older than flag leaf. The number of epidermal cells primarily determined the differences in FLL and FLW. In addition, we identified the previously unknown effect of genic- and epiallele at Vrn-H1 on flag leaf size variation in spring barley. Furthermore, we fine-mapped qHvDRR-FLS-8, narrowing the interval from 8.7 to 3.5 Mb. In conclusion, our study identified the genomic regions associated with morphological and anatomical variation for leaf size and set the stage to uncover causal genes.

genetics↗

bioRxiv2025

Optogenetic translocation to subcellular compartments through regulation of protein avidity

Inducible translocation to subcellular compartments is a common strategy for protein switches that control a variety of cell behaviors. However, existing switches achieve translocation through induced dimerization, requiring constitutive anchoring of one component into the target compartment and optimization of relative expression levels between the two components. We present a simpler, single-component strategy called Avidity-assisted targeting (Aviatar). Aviatar achieves translocation with only a single protein by converting low-affinity monomers into high-avidity assemblies through inducible clustering. We demonstrated the Aviatar concept and its generality using optogenetic clustering to drive translocation to the plasma membrane, endosomes, golgi, endoplasmic reticulum, and microtubules using binding domains for lipids or endogenous proteins that were specific to those compartments. Aviatar recruitment regulated actin polymerization at the cell periphery and revealed compartment-specific signaling of receptor tyrosine kinase fusions associated with cancer. Finally, GFP-targeting Aviatar probes allowed inducible localization to any GFP-tagged target, including endogenously-tagged stress granule proteins. Aviatar is a straightforward platform that can be rapidly adapted to a broad array of targets without the need for their prior modification or disruption.

bioengineering↗

bioRxiv2025

Inulin reduces Ralstonia invasion by promoting cooperation between Lysinibacillus sphaericus and Pseudoarthrobacter spp.

In field production, beneficial microbial agents are typically applied along with key resources that beneficial microbes prefer to utilize. This practice aims to help the beneficial microbes colonize the field and exert their disease resistance functions. However, the mechanisms by which these key resources influence the colonization and disease resistance effects of beneficial microbes remain unknown. In this study, we found that inulin can enhance the growth capacity of Lysinibacillus sphaericus HR92 and its ability to inhibit Ralstonia solanacearum. Further investigation revealed that inulin can enhance strain HR92s flagellar assembly, bacterial chemotaxis, fatty acid metabolism, and siderophore synthesis capabilities, ultimately improving strain HR92s effectiveness in controlling bacterial wilt. Moreover, adding inulin to the soil can enrich Pseudarthrobacter strains. This genus enhances the expression of genes involved in the synthesis of the antibacterial substance HR92, and competes for nutrients with Ralstonia solanacearum, thereby further inhibiting the occurrence of bacterial wilt disease. Additionally, the combination of inulin and Pseudarthrobacter strains upregulates the valine and leucine pathway genes in strain HR92. These genes play a crucial role in the synthesis of surfactin and the antimicrobial VOC 3-methyl-1-butanol. We have demonstrated that the addition of key resources not only enhances the control efficacy of beneficial bacteria against soil-borne diseases but also enriches the "helpers" of beneficial bacteria in soil. ImportanceRalstonia solanacearum is a plant pathogen that can cause bacterial wilt in several important crops. Given the limitations of beneficial bacterial inoculation, we propose a strategy to enhance the biocontrol efficacy of beneficial microorganisms by utilizing key resources. In this study, we demonstrate that key resources inulin can improve the biological control effects of beneficial bacteria, thereby maintaining plant health. Furthermore, we found that increasing the concentration of inulin altered the diversity of the rhizosphere microbiota and specifically enriched the abundance of Pseudarthrobacter, which compete with pathogens for nutrients on one hand and, on the other hand, synergize with inulin to enhance the biocontrol efficacy of the beneficial bacterium HR92. Together, our study reveals that key resources can enhance the biocontrol efficacy of beneficial bacteria and enrich potential beneficial bacteria in resident microbial communities, further reducing tomato diseases.

microbiology↗

bioRxiv2025

Theoretical origins of extreme cell differentiation irreversibility: a dynamic model of organismal size effects

Cell differentiation is a pivotal evolutionary transition underlying multicellular complexity. Irreversible differentiation - a process in which cells permanently lose plasticity to become specialized types - is hypothesized to emerge predominantly in large, cell-rich organisms. However, the causal relationship between organismal size and the evolutionary origins of this extreme developmental commitment remains unclear. By integrating developmental dynamics into a mathematical model, we demonstrate that extreme irreversible differentiation (where all cell types exhibit irreversibility) most robustly evolves in intermediately sized multicellularity. This reveals a non-monotonic dependence of cell fate determinism on an organismal scale. Specifically, increasing organismal size initially promotes extreme irreversible differentiation by enhancing the selective advantages of cellular division of labor. Beyond a critical size threshold, however, further expansion destabilizes this extreme irreversibility due to its decreasing differentiation advantages compared with reversible differentiation. Counterintuitively, smaller organisms establish cellular irreversibility at earlier developmental stages rather than larger organisms. Our framework identifies an evolutionary double-edged sword: while body size expansion initially facilitates extreme differentiation irreversibility, it ultimately leads to its collapse. These results establish quantitative links between organismal dimensions and cell fate determinism, explaining the size-dependent evolution of developmental strategies in simple multicellular systems.

evolutionary biology↗

bioRxiv2025

Tissue-wide profiling of human lungs reveals spatial sequestration of macrophages in tuberculosis

The immune response to human tuberculosis (TB), particularly in the context of complex lung pathology, remains incompletely understood. Here, we employed whole-slide spatial proteomics to map immune cell organization in TB-affected human lung tissues. Our analysis revealed pronounced spatial segregation of major immune cell populations in non-necrotizing TB lesions. At the tissue level, macrophages and lymphocytes formed distinct cellular communities associated with specific pathological features. At the lesion level, macrophages and B cells showed an inverse relationship in both abundance and spatial distribution. Proinflammatory T cells preferentially accumulated in macrophage-rich lesions but remained largely separated from macrophages. Interestingly, lesions exhibiting clear segregation between T cells and macrophages were more common in subclinical TB than in active disease. These findings suggest that spatial isolation of macrophages from effector lymphocytes may help temper inflammation and potentially prevent lesion progression to necrosis, while also enabling immune evasion by Mycobacterium tuberculosis. One Sentence SummaryXiao et al. reveal spatial segregation of immune cells in TB-lung tissue and link the microenvironmental dynamics to disease states of tuberculosis.

immunology↗

bioRxiv2025

ERK and PKA signaling drive the evolutionary expansion of the cortex

The human cerebral cortex, essential for intelligence, cognition, and language, evolved its uniqueness through mechanisms that drive neuronal expansion. Here, we demonstrate that ERK and PKA signaling cooperatively preserve the neurogenic capacity of cortical radial glia (RGs) by inhibiting gliogenic YAP/TAZ and SHH signaling. YAP/TAZ signaling drives cortical RGs toward ependymal fate, while SHH signaling facilitates the generation of cortical tripotential intermediate progenitor cells that produce cortical astrocytes, oligodendrocytes, and olfactory bulb interneurons. During evolution, cortical outer radial glia (oRGs) acquire dominant ERK/PKA signaling through a self-reinforcing feedback mechanism that suppresses both YAP and SHH pathways, thereby significantly enhancing oRG self-renewal capacity and extending the neurogenic period. These findings reveal that cortical neurogenesis, gliogenesis, and evolutionary expansion are coordinately regulated by an integrated ERK, PKA, YAP/TAZ, and SHH signaling, identifying a unifying principle of mammalian cortical development and evolution.

developmental biology↗

bioRxiv2025

Benchmarking single-cell multi-modal data integrations

Single-cell multi-modal omics, remarked as "Method of the Year 2019" by Nature Methods, provides valuable insights into complex tissues. Recent advances have enabled the generation both unpaired (separate profiling) and paired (simultaneous measurement) multi-modal datasets, driving rapid development of single-cell multi-modal integration tools. Nevertheless, there is a pressing need for a comprehensive benchmark to assess algorithms under varying integrated dataset types, integrated modalities, dataset sizes, and data quality. Here, we present a systematic benchmark for 40 single-cell multi-modal integration algorithms involving modalities of DNA, RNA, protein and spatial omics for paired, unpaired and mosaic datasets (a mixture of paired and unpaired datasets). We evaluated usability, accuracy, and robustness to assist researchers in selecting suitable integration methods tailored to their datasets and applications. Our benchmark provides valuable guidance in the ever-evolving field of single-cell multi-omics. The Stage 1 protocol for this Registered Report was accepted in principle on 3rd Jul 2024. The protocol, as accepted by the journal, can be found at https://springernature.figshare.com/articles/journal_contribution/Benchmarking_single-cell_multi-modal_data_integrations/26789572.

bioinformatics↗

bioRxiv2025

Comparison of Urinary Proteome Modifications Between Methamphetamine-Abstinent Rehabilitation Patients for Over Three Months and Healthy Individuals

Methamphetamine addiction is characterized by complex mechanisms and a high relapse rate, posing a serious public health threat. In this study, urinary proteome modifications of rehabilitation patients who had abstained from methamphetamine for over three months and those of healthy individuals were analyzed and compared. A total of 984 differentially modified peptides were identified, 362 of which showed changes from presence to absence or vice versa. Results from the randomized grouping test indicated that at least 74.85% of these differentially modified peptides were not randomly generated. Several proteins containing these peptides have been reported to be associated with methamphetamine, including prostaglandin-H2 D-isomerase, complement factor H, filamin-A, and plasminogen. Additionally, some significantly changed modified peptides and the proteins they are located in, which have not been previously reported to be associated with methamphetamine, may provide new insights into addiction rehabilitation. This study establishes a method for investigating drug addiction through urinary proteome modifications and observes differences between methamphetamine-abstinent rehabilitation patients and healthy individuals, which may help explain the drugs high relapse rate. It offers a new perspective on drug withdrawal research and holds potential for tracking and assessing the rehabilitation process of methamphetamine addiction.

biochemistry↗