RESUMEN
Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.
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Progresión de la Enfermedad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteogenómica , Fumar/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinógenos/toxicidad , Estudios de Cohortes , Citosina Desaminasa/metabolismo , Asia Oriental , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Genoma Humano , Humanos , Metaloproteinasas de la Matriz/metabolismo , Mutación/genética , Análisis de Componente PrincipalRESUMEN
The reprogramming factors that induce pluripotency have been identified primarily from embryonic stem cell (ESC)-enriched, pluripotency-associated factors. Here, we report that, during mouse somatic cell reprogramming, pluripotency can be induced with lineage specifiers that are pluripotency rivals to suppress ESC identity, most of which are not enriched in ESCs. We found that OCT4 and SOX2, the core regulators of pluripotency, can be replaced by lineage specifiers that are involved in mesendodermal (ME) specification and in ectodermal (ECT) specification, respectively. OCT4 and its substitutes attenuated the elevated expression of a group of ECT genes, whereas SOX2 and its substitutes curtailed a group of ME genes during reprogramming. Surprisingly, the two counteracting lineage specifiers can synergistically induce pluripotency in the absence of both OCT4 and SOX2. Our study suggests a "seesaw model" in which a balance that is established using pluripotency factors and/or counteracting lineage specifiers can facilitate reprogramming.
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Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Factores de Transcripción/metabolismo , Animales , Células Madre Embrionarias/metabolismo , Fibroblastos/metabolismo , Factor de Transcripción GATA3/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Ratones , Modelos Biológicos , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Estómago/citologíaRESUMEN
Somatic mutations that accumulate in normal tissues are associated with ageing and disease1,2. Here we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies of 9 organs from 5 donors. We found that somatic mutation accumulations and clonal expansions were widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for in tissues from the oesophagus and cardia. Endogenous mutational processes with the SBS1 and SBS5 mutational signatures are ubiquitous among normal tissues, although they exhibit different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimetre resolution. In the oesophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometres were frequently seen, whereas in tissues such as the colon, rectum and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue microstructures. Our study depicts a body map of somatic mutations and clonal expansions from the same individual.
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Células Clonales/metabolismo , Salud , Mutagénesis , Mutación , Especificidad de Órganos , Anciano de 80 o más Años , Biopsia , Cadáver , Cardias/metabolismo , Proliferación Celular , Células Clonales/citología , Esófago/metabolismo , Femenino , Genómica , Humanos , MasculinoRESUMEN
The tandem Tudor-like domain-containing protein Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in embryonic development and emerging roles in cancer. However, the involvement of SPIN1 in DNA damage repair has remained unclear. Our study shows that SPIN1 is recruited to DNA lesions through its N-terminal disordered region that binds to Poly-ADP-ribose (PAR), and facilitates homologous recombination (HR)-mediated DNA damage repair. SPIN1 promotes H3K9me3 accumulation at DNA damage sites and enhances the interaction between H3K9me3 and Tip60, thereby promoting the activation of ATM and HR repair. We also show that SPIN1 increases chemoresistance. These findings reveal a novel role for SPIN1 in the activation of H3K9me3-dependent DNA repair pathways, and suggest that SPIN1 may contribute to cancer chemoresistance by modulating the efficiency of double-strand break (DSB) repair.
RESUMEN
The exonuclease ISG20L2 has been initially characterized for its role in the mammalian 5.8S rRNA 3' end maturation, specifically in the cleavage of ITS2 of 12S precursor ribosomal RNA (pre-rRNA). Here, we show that human ISG20L2 is also involved in 18S pre-rRNA maturation through removing the ITS1 region, and contributes to ribosomal biogenesis and cell proliferation. Furthermore, we determined the crystal structure of the ISG20L2 nuclease domain at 2.9 Å resolution. It exhibits the typical αßα fold of the DEDD 3'-5' exonuclease with a catalytic pocket located in the hollow near the center. The catalytic residues Asp183, Glu185, Asp267, His322 and Asp327 constitute the DEDDh motif in ISG20L2. The active pocket represents conformational flexibility in the absence of an RNA substrate. Using structural superposition and mutagenesis assay, we mapped RNA substrate binding residues in ISG20L2. Finally, cellular assays revealed that ISG20L2 is aberrantly up-regulated in colon adenocarcinoma and promotes colon cancer cell proliferation through regulating ribosome biogenesis. Together, these results reveal that ISG20L2 is a new enzymatic member for 18S pre-rRNA maturation, provide insights into the mechanism of ISG20L2 underlying pre-rRNA processing, and suggest that ISG20L2 is a potential therapeutic target for colon adenocarcinoma.
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Adenocarcinoma , Neoplasias del Colon , Animales , Humanos , ARN Ribosómico 18S/metabolismo , Precursores del ARN/genética , Precursores del ARN/metabolismo , Adenocarcinoma/genética , Neoplasias del Colon/genética , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , Ribosomas/genética , Ribosomas/metabolismo , Procesamiento Postranscripcional del ARN , Exonucleasas/genética , Exonucleasas/metabolismo , ARN Ribosómico 5.8S/genética , Mamíferos/genéticaRESUMEN
The past 4 decades have witnessed tremendous efforts in deciphering the role of O-GlcNAcylation in a plethora of biological processes. Chemists and biologists have joined hand in hand in the sweet adventure to unravel this unique and universal yet uncharted post-translational modification, and the recent advent of cutting-edge chemical biology and mass spectrometry tools has greatly facilitated the process. Compared with O-GlcNAc, DNA damage response (DDR) is a relatively intensively studied area that could be traced to before the elucidation of the structure of DNA. Unexpectedly, yet somewhat expectedly, O-GlcNAc has been found to regulate various DDR pathways: homologous recombination, nonhomologous end joining, base excision repair, and translesion DNA synthesis. In this review, we first cover the recent structural studies of the O-GlcNAc transferase and O-GlcNAcase, the elegant duo that "writes" and "erases" O-GlcNAc modification. Then we delineate the intricate roles of O-GlcNAc transferase and O-GlcNAcase in DDR. We envision that this is only the beginning of our full appreciation of how O-GlcNAc regulates the blueprint of life-DNA.
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N-Acetilglucosaminiltransferasas , Animales , Humanos , beta-N-Acetilhexosaminidasas/metabolismo , beta-N-Acetilhexosaminidasas/genética , ADN/metabolismo , ADN/química , Daño del ADN , Reparación del ADN , N-Acetilglucosaminiltransferasas/metabolismo , N-Acetilglucosaminiltransferasas/genética , Procesamiento Proteico-Postraduccional , GenomaRESUMEN
Polyploidization and polyploidy reversal (depolyploidization) are crucial pathways to conversely alter genomic contents in organisms. Understanding the mechanisms switching between polyploidization and polyploidy reversal should broaden our knowledge of the generation of pathological polyploidy and pave a new path to prevent related diseases.
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Mitosis , Poliploidía , HumanosRESUMEN
Genomic-scale somatic copy number alterations in healthy humans are difficult to investigate because of low occurrence rates and the structural variations' stochastic natures. Using a Tn5-transposase-assisted single-cell whole-genome sequencing method, we sequenced over 20,000 single lymphocytes from 16 individuals. Then, with the scale increased to a few thousand single cells per individual, we found that about 7.5% of the cells had large-size copy number alterations. Trisomy 21 was the most prevalent aneuploid event among all autosomal copy number alterations, whereas monosomy X occurred most frequently in over-30-yr-old females. In the monosomy X single cells from individuals with phased genomes and identified X-inactivation ratios in bulk, the inactive X Chromosomes were lost more often than the active ones.
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Variaciones en el Número de Copia de ADN , Genómica , Aneuploidia , Femenino , Humanos , Linfocitos , Secuenciación Completa del GenomaRESUMEN
SUMMARY: Genome assembly projects have grown exponentially due to breakthroughs in sequencing technologies and assembly algorithms. Evaluating the quality of genome assemblies is critical to ensure the reliability of downstream analysis and interpretation. To fulfil this task, we have developed the AssemblyQC pipeline that performs file-format validation, contaminant checking, contiguity measurement, gene- and repeat-space completeness quantification, telomere inspection, taxonomic assignment, synteny alignment, scaffold examination through Hi-C contact-map visualization, and assessments of completeness, consensus quality and phasing through k-mer analysis. It produces a comprehensive HTML report with method descriptions, tables, and visualizations. AVAILABILITY AND IMPLEMENTATION: The pipeline uses Nextflow for workflow orchestration and adheres to the best-practice established by the nf-core community. This pipeline offers a reproducible, scalable, and portable method to assess the quality of genome assemblies-the code is available online at GitHub: https://github.com/Plant-Food-Research-Open/assemblyqc.
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Programas Informáticos , Análisis de Secuencia de ADN/métodos , Algoritmos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Genoma , Genómica/métodosRESUMEN
Fibrillarin (FBL) is a highly conserved nucleolar methyltransferase responsible for methylation of ribosomal RNA and proteins. Here, we reveal a role for FBL in DNA damage response and its impact on cancer proliferation and sensitivity to DNA-damaging agents. FBL is highly expressed in various cancers and correlates with poor survival outcomes in cancer patients. Knockdown of FBL sensitizes tumor cells and xenografts to DNA crosslinking agents, and leads to homologous recombination-mediated DNA repair defects. We identify Y-box-binding protein-1 (YBX1) as a key interacting partner of FBL, and FBL increases the nuclear accumulation of YBX1 in response to DNA damage. We show that FBL promotes the expression of BRCA1 by increasing the binding of YBX1 to the BRCA1 promoter. Our study sheds light on the regulatory mechanism of FBL in tumorigenesis and DNA damage response, providing potential therapeutic targets to overcome chemoresistance in cancer.
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Antineoplásicos , Neoplasias , Humanos , Neoplasias/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Antineoplásicos/uso terapéutico , Daño del ADN , Línea Celular Tumoral , Proteína 1 de Unión a la Caja Y/genética , Proteína 1 de Unión a la Caja Y/metabolismo , Proteína BRCA1/genéticaRESUMEN
We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific beta-tubulin isotype III, result in a spectrum of human nervous system disorders that we now call the TUBB3 syndromes. Each mutation causes the ocular motility disorder CFEOM3, whereas some also result in intellectual and behavioral impairments, facial paralysis, and/or later-onset axonal sensorimotor polyneuropathy. Neuroimaging reveals a spectrum of abnormalities including hypoplasia of oculomotor nerves and dysgenesis of the corpus callosum, anterior commissure, and corticospinal tracts. A knock-in disease mouse model reveals axon guidance defects without evidence of cortical cell migration abnormalities. We show that the disease-associated mutations can impair tubulin heterodimer formation in vitro, although folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter dynamic instability whereas a subset disrupts the interaction of microtubules with kinesin motors. These findings demonstrate that normal TUBB3 is required for axon guidance and maintenance in mammals.
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Tubulina (Proteína)/metabolismo , Secuencia de Aminoácidos , Animales , Axones/metabolismo , Encéfalo/embriología , Encéfalo/metabolismo , Supervivencia Celular , Niño , Discapacidades del Desarrollo , Femenino , Humanos , Cinesinas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Microtúbulos/metabolismo , Modelos Moleculares , Datos de Secuencia Molecular , Mutación Missense , Transporte de Proteínas , Tubulina (Proteína)/química , Tubulina (Proteína)/genéticaRESUMEN
Nucleic acid ADP-ribosylation has been established as a novel modification found in a wide diversity of prokaryotic and eukaryotic organisms. tRNA 2'-phosphotransferase 1 (TRPT1/TPT1/KptA) possesses ADP-ribosyltransferase (ART) activity and is able to ADP-ribosylate nucleic acids. However, the underlying molecular mechanism remains elusive. Here, we determined crystal structures of TRPT1s in complex with NAD+ from Homo sapiens, Mus musculus and Saccharomyces cerevisiae. Our results revealed that the eukaryotic TRPT1s adopt common mechanisms for both NAD+ and nucleic acid substrate binding. The conserved SGR motif induces a significant conformational change in the donor loop upon NAD+ binding to facilitate the catalytic reaction of ART. Moreover, the nucleic acid-binding residue redundancy provides structural flexibility to accommodate different nucleic acid substrates. Mutational assays revealed that TRPT1s employ different catalytic and nucleic acid-binding residues to perform nucleic acid ADP-ribosylation and RNA 2'-phosphotransferase activities. Finally, cellular assays revealed that the mammalian TRPT1 is able to promote endocervical HeLa cell survival and proliferation. Together, our results provide structural and biochemical insights into the molecular mechanism of TRPT1 for nucleic acid ADP-ribosylation.
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Fosfotransferasas (Aceptor de Grupo Alcohol) , Proteínas de Saccharomyces cerevisiae , Animales , Humanos , Ratones , Adenosina Difosfato Ribosa/metabolismo , ADP Ribosa Transferasas/genética , ADP Ribosa Transferasas/metabolismo , ADP-Ribosilación , Células HeLa , NAD/metabolismo , Ácidos Nucleicos/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/química , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, a prevalent protein post-translational modification (PTM) that occurs intracellularly, has been shown to crosstalk with phosphorylation and ubiquitination. However, it is unclear whether it interplays with other PTMs. Here we studied its relationship with ADP-ribosylation, which involves decorating target proteins with the ADP-ribose moiety. We discovered that the poly(ADP-ribosyl)ation "eraser", ADP-ribose glycohydrolase (PARG), is O-GlcNAcylated at Ser26, which is in close proximity to its nuclear localization signal. O-GlcNAcylation of PARG promotes nuclear localization and chromatin association. Upon DNA damage, O-GlcNAcylation augments the recruitment of PARG to DNA damage sites and interacting with proliferating cell nuclear antigen (PCNA). In hepatocellular carcinoma (HCC) cells, PARG O-GlcNAcylation enhances the poly(ADP-ribosyl)ation of DNA damage-binding protein 1 (DDB1) and attenuates its auto-ubiquitination, thereby stabilizing DDB1 and allowing it to degrade its downstream targets, such as c-Myc. We further demonstrated that PARG-S26A, the O-GlcNAc-deficient mutant, promoted HCC in mouse xenograft models. Our findings thus reveal that PARG O-GlcNAcylation inhibits HCC, and we propose that O-GlcNAc glycosylation may crosstalk with many other PTMs.
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Carcinoma Hepatocelular , Glicósido Hidrolasas , Neoplasias Hepáticas , Animales , Humanos , Ratones , Acetilglucosamina , ADP-Ribosilación , Glicósido Hidrolasas/genética , Glicósido Hidrolasas/metabolismo , Poli Adenosina Difosfato Ribosa/metabolismo , Glicosilación , Procesamiento Proteico-PostraduccionalRESUMEN
Dihydrochalcones (DHCs) including phlorizin (phloretin 2'-O-glucoside) and its positional isomer trilobatin (phloretin 4'-O-glucoside) are the most abundant phenylpropanoids in apple (Malus spp.). Transcriptional regulation of DHC production is poorly understood despite their importance in insect- and pathogen-plant interactions in human physiology research and in pharmaceuticals. In this study, segregation in hybrid populations and bulked segregant analysis showed that the synthesis of phlorizin and trilobatin in Malus leaves are both single-gene-controlled traits. Promoter sequences of PGT1 and PGT2, two glycosyltransferase genes involved in DHC glycoside synthesis, were shown to discriminate Malus with different DHC glycoside patterns. Differential PGT1 and PGT2 promoter activities determined DHC glycoside accumulation patterns between genotypes. Two transcription factors containing MYB-like DNA-binding domains were then shown to control DHC glycoside patterns in different tissues, with PRR2L mainly expressed in leaf, fruit, flower, stem, and seed while MYB8L mainly expressed in stem and root. Further hybridizations between specific genotypes demonstrated an absolute requirement for DHC glycoside production in Malus during seed development which explains why no Malus spp. with a null DHC chemotype have been reported.
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Malus , Humanos , Malus/genética , Florizina , Factores de Transcripción/genética , Floretina , Semillas/genética , Glucósidos , Regulación de la Expresión Génica de las PlantasRESUMEN
Cell surface hydrophobicity (CSH) dominates the interactions between rhizobacteria and pollutants at the soil-water interface, which is critical for understanding the dissipation of pollutants in the rhizosphere microzone of rice. Herein, we explored the effects of self-adaptive CSH of Sphingomonas sp. strain PAH02 on the translocation and biotransformation behaviour of cadmium-phenanthrene (Cd-Phe) co-pollutant in rice and rhizosphere microbiome. We evidenced that strain PAH02 reduced the adsorption of Cd-Phe co-pollutant on the rice root surface while enhancing the degradation of Phe and adsorption of Cd via its self-adaptive CSH in the hydroponic experiment. The significant upregulation of key protein expression levels such as MerR, ARHDs and enoyl-CoA hydratase/isomerase, ensures self-adaptive CSH to cope with the stress of Cd-Phe co-pollutant. Consistently, the bioaugmentation of strain PAH02 promoted the formation of core microbiota in the rhizosphere soil of rice (Oryza sativa L.), such as Bradyrhizobium and Streptomyces and induced gene enrichment of CusA and PobA that are strongly associated with pollutant transformation. Consequently, the contents of Cd and Phe in rice grains at maturity decreased by 17.2% ± 0.2% and 65.7% ± 0.3%, respectively, after the bioaugmentation of strain PAH02. These findings present new opportunities for the implementation of rhizosphere bioremediation strategies of co-contaminants in paddy fields.
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Contaminantes Ambientales , Oryza , Fenantrenos , Contaminantes del Suelo , Sphingomonas , Cadmio/metabolismo , Oryza/metabolismo , Contaminantes Ambientales/metabolismo , Sphingomonas/genética , Sphingomonas/metabolismo , Proteómica , Contaminantes del Suelo/metabolismo , Fenantrenos/metabolismo , Suelo , RizosferaRESUMEN
Immunochromatography is a commonly used immediate detection technique, using signal labels to generate detection signals for rapid medical diagnosis. However, its detection sensitivity is affected by background fluorescence caused by the excitation light source. We have developed an immunochromatographic test strip using Zn2GeO4:Mn2+ (ZGM) persistent luminescent nanoparticles (PLNPs) for immediate fluorescence detection and highly sensitive persistent luminescence (PersL) detection without background fluorescence interference. ZGM emits a strong green light when exposed to ultraviolet (UV) excitation, and its green PersL can persist for over 30 min after the excitation light is turned off. We modified the surface of ZGM with heparin-binding protein (HBP) antibodies to create immunochromatographic test strips for the detection of HBP as the target analyte. Under UV excitation, the chromatography test paper can be visually observed at concentrations as low as 25 ng/mL. After the excitation light source is switched off, PersL can achieve a detection limit of 4.7 ng/mL without background interference. This dual-mode immunochromatographic detection, based on ZGM, shows great potential for in vitro diagnostic applications.
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Germanio , Luminiscencia , Nanopartículas , Nanopartículas/química , Óxidos , Cromatografía de Afinidad/métodosRESUMEN
MOTIVATION: Digital pathological analysis is run as the main examination used for cancer diagnosis. Recently, deep learning-driven feature extraction from pathology images is able to detect genetic variations and tumor environment, but few studies focus on differential gene expression in tumor cells. RESULTS: In this paper, we propose a self-supervised contrastive learning framework, HistCode, to infer differential gene expression from whole slide images (WSIs). We leveraged contrastive learning on large-scale unannotated WSIs to derive slide-level histopathological features in latent space, and then transfer it to tumor diagnosis and prediction of differentially expressed cancer driver genes. Our experiments showed that our method outperformed other state-of-the-art models in tumor diagnosis tasks, and also effectively predicted differential gene expression. Interestingly, we found the genes with higher fold change can be more precisely predicted. To intuitively illustrate the ability to extract informative features from pathological images, we spatially visualized the WSIs colored by the attention scores of image tiles. We found that the tumor and necrosis areas were highly consistent with the annotations of experienced pathologists. Moreover, the spatial heatmap generated by lymphocyte-specific gene expression patterns was also consistent with the manually labeled WSIs.
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Neoplasias , Oncogenes , Humanos , Aprendizaje Automático , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patologíaRESUMEN
PURPOSE: Lower urinary tract symptoms (LUTS) are a challenge to the healthy nursing workforce. Nurses confront various objective and subjective nursing workloads which contribute to their LUTS, but less is known about how nursing workloads influence their LUTS. This study is designed to test hypotheses that delayed voiding behaviors mediate the relationships between nursing workloads and LUTS in female nurses. MATERIALS AND METHODS: This study analyzed the baseline data collected from an ongoing cohort study named Nurse Urinary Related Health Study in China. LUTS of nurses in 20 tertiary hospitals were assessed with the International Consultation on Incontinence QuestionnaireâFemale Lower Urinary Tract Symptoms. Objective nursing workloads including working environment, working hours, and working schedule were collected, and perceived stress, the proxy of the subjective nursing workload, was assessed with the Perceived Stress Scale. Delayed voiding behaviors were assessed with 3 questions adapted from the Taiwan Nurse Bladder Survey. Structural equation modeling was used to run the mediation model. RESULTS: More than half (51%) of 13,191 female nurses had LUTS. Median age was 31 years (IQR 27-37). When delayed voiding behaviors served as a mediator, the direct effects of subjective nursing workload rather than objective nursing workloads on LUTS were significant. CONCLUSIONS: Nursing workloads influence nurses' LUTS via delayed voiding behaviors. Strategies tailored to delayed voiding behaviors should be developed, and these may work with stress-reducing strategies as the gatekeepers for nurses' bladder health.
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Síntomas del Sistema Urinario Inferior , Pruebas Psicológicas , Autoinforme , Carga de Trabajo , Humanos , Femenino , Adulto , Estudios de Cohortes , Síntomas del Sistema Urinario Inferior/epidemiología , Encuestas y Cuestionarios , China/epidemiologíaRESUMEN
With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.