Int J Mol Sci. 2024 Oct 7;25(19):10768. doi: 10.3390/ijms251910768.

ABSTRACT

Pediatric genetic epilepsies, such as CDKL5 Deficiency Disorder (CDD), are severely debilitating, with early-onset seizures occurring more than ten times daily in extreme cases. Existing antiseizure drugs frequently prove ineffective, which significantly impacts child development and diminishes the quality of life for patients and caregivers. The relaxation of cannabis legislation has increased research into potential therapeutic properties of phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). CBD's antiseizure properties have shown promise, particularly in treating drug-resistant genetic epilepsies associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). However, specific research on CDD remains limited. Much of the current evidence relies on anecdotal reports of artisanal products lacking accurate data on cannabinoid composition. Utilizing model systems like patient-derived iPSC neurons and brain organoids allows precise dosing and comprehensive exploration of cannabinoids' pharmacodynamics. This review explores the potential of CBD, THC, and other trace cannabinoids in treating CDD and focusing on clinical trials and preclinical models to elucidate the cannabinoid's potential mechanisms of action in disrupted CDD pathways and strengthen the case for further research into their potential as anti-epileptic drugs for CDD. This review offers an updated perspective on cannabinoid's therapeutic potential for CDD.

PMID:39409097 | DOI:10.3390/ijms251910768

Int J Mol Sci. 2024 Oct 4;25(19):10691. doi: 10.3390/ijms251910691.

ABSTRACT

This study aimed to construct genome-wide genetic and epigenetic networks (GWGENs) of atopic dermatitis (AD) and healthy controls through systems biology methods based on genome-wide microarray data. Subsequently, the core GWGENs of AD and healthy controls were extracted from their real GWGENs by the principal network projection (PNP) method for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. Then, we identified the abnormal signaling pathways by comparing the core signaling pathways of AD and healthy controls to investigate the pathogenesis of AD. Then, IL-1β, GATA3, Akt, and NF-κB were selected as biomarkers for their important roles in the abnormal regulation of downstream genes, leading to cellular dysfunctions in AD patients. Next, a deep neural network (DNN)-based drug-target interaction (DTI) model was pre-trained on DTI databases to predict molecular drugs that interact with these biomarkers. Finally, we screened the candidate molecular drugs based on drug toxicity, sensitivity, and regulatory ability as drug design specifications to select potential molecular drugs for these biomarkers to treat AD, including metformin, allantoin, and U-0126, which have shown potential for therapeutic treatment by regulating abnormal immune responses and restoring the pathogenic signaling pathways of AD.

PMID:39409019 | DOI:10.3390/ijms251910691

Int J Mol Sci. 2024 Oct 1;25(19):10600. doi: 10.3390/ijms251910600.

ABSTRACT

The landscape of clinical management for metastatic melanoma (MM) and other solid tumors has been modernized by the advent of immune checkpoint inhibitors (ICI), including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. While these agents demonstrate efficacy in suppressing tumor growth, they also lead to immune-related adverse events (irAEs), resulting in the exacerbation of autoimmune diseases such as rheumatoid arthritis (RA), ulcerative colitis (UC), and Crohn's disease (CD). The immune checkpoint inhibitors offer promising advancements in the treatment of melanoma and other cancers, but they also present significant challenges related to irAEs and autoimmune diseases. Ongoing research is crucial to better understand these challenges and develop strategies for mitigating adverse effects while maximizing therapeutic benefits. In this manuscript, we addressed this challenge using network-based approaches by constructing and analyzing the molecular and signaling networks associated with tumor-immune crosstalk. Our analysis revealed that IL6 is the key regulator responsible for irAEs during ICI therapies. Furthermore, we conducted an integrative network and molecular-level analysis, including virtual screening, of drug libraries, such as the Collection of Open Natural Products (COCONUT) and the Zinc15 FDA-approved library, to identify potential IL6 inhibitors. Subsequently, the compound amprenavir was identified as the best molecule that may disrupt essential interactions between IL6 and IL6R, which are responsible for initiating the signaling cascades underlying irAEs in ICI therapies.

PMID:39408929 | DOI:10.3390/ijms251910600

Int J Mol Sci. 2024 Sep 28;25(19):10468. doi: 10.3390/ijms251910468.

ABSTRACT

Iron plays a crucial role in various metabolic processes. However, the impact of 5-aminolevulinic acid (ALA) in combination with iron chelators on iron metabolism and the efficacy of ALA-photodynamic therapy (PDT) remain inadequately understood. This study aimed to examine the effect of thiosemicarbazone derivatives during ALA treatment on specific genes related to iron metabolism, with a particular emphasis on mitochondrial iron metabolism genes. In our study, we observed differences depending on the cell line studied. For the HCT116 and MCF-7 cell lines, in most cases, the decrease in the expression of selected targets correlated with the increase in protoporphyrin IX (PPIX) concentration and the observed photodynamic effect, aligning with existing literature data. The Hs683 cell line showed a different gene expression pattern, previously not described in the literature. In this study, we collected an extensive analysis of the gene variation occurring after the application of novel thiosemicarbazone derivatives and presented versatile and effective compounds with great potential for use in ALA-PDT.

PMID:39408796 | DOI:10.3390/ijms251910468

Int J Mol Sci. 2024 Sep 27;25(19):10417. doi: 10.3390/ijms251910417.

ABSTRACT

Bone health is ensured by the coordinated action of two types of cells-the osteoblasts that build up bone structure and the osteoclasts that resorb the bone. The loss of balance in their action results in pathological conditions such as osteoporosis. Central to this study is a class of RNA-binding proteins (RBPs) that regulates the biogenesis of miRNAs. In turn, miRNAs represent a critical level of regulation of gene expression and thus control multiple cellular and biological processes. The impact of miRNAs on the pathobiology of various multifactorial diseases, including osteoporosis, has been demonstrated. However, the role of RBPs in bone remodeling is yet to be elucidated. The aim of this study is to dissect the transcriptional landscape of genes encoding the compendium of 180 RBPs in bone cells. We developed and applied a multi-modular integrative analysis algorithm. The core methodology is gene expression analysis using the GENEVESTIGATOR platform, which is a database and analysis tool for manually curated and publicly available transcriptomic data sets, and gene network reconstruction using the Ingenuity Pathway Analysis platform. In this work, comparative insights into gene expression patterns of RBPs in osteoblasts and osteoclasts were obtained, resulting in the identification of 24 differentially expressed genes. Furthermore, the regulation patterns upon different treatment conditions revealed 20 genes as being significantly up- or down-regulated. Next, novel gene-gene associations were dissected and gene networks were reconstructed. Additively, a set of osteoblast- and osteoclast-specific gene signatures were identified. The consolidation of data and information gained from each individual analytical module allowed nominating novel promising candidate genes encoding RBPs in osteoblasts and osteoclasts and will significantly enhance the understanding of potential regulatory mechanisms directing intracellular processes in the course of (patho)physiological bone turnover.

PMID:39408753 | DOI:10.3390/ijms251910417

Int J Mol Sci. 2024 Sep 27;25(19):10407. doi: 10.3390/ijms251910407.

ABSTRACT

Ant evolutionary success depends mainly on the coordination of colony members, who recognize nestmates based on the cuticular hydrocarbon (CHC) profile of their epicuticle. While several studies have examined variations in this crucial factor for colony identity, few have investigated the anthropic impact on CHC profiles, and none have focused on Lasius paralienus. Here, we surveyed the changes in L. paralienus CHC assemblages across agroecosystems and assessed whether different vineyard management influences these profiles. Soil sampling within ant nests and in close surroundings was performed to measure microhabitat variations. Our results show that the cuticular chemical composition of Lasius paralienus is mainly affected by the differences between areas, with an existing but unclear anthropic influence on them. Normalized soil respiration partially explains these interarea variations. Irrespective of the conventional or organic management, human activities in agroecosystems mostly impacted L. paralienus linear alkanes, a specific class of CHCs known to play a major role against dehydration, but also affected the abundance of compounds that can be pivotal for maintaining the colony identity. Our findings suggest that vineyard practices primarily affect features of the ant cuticle, potentially enhancing microclimate adaptations. Still, the potential effects as disruptive factors need further investigation through the implementation of behavioral bioassays.

PMID:39408736 | DOI:10.3390/ijms251910407

Int J Mol Sci. 2024 Sep 26;25(19):10367. doi: 10.3390/ijms251910367.

ABSTRACT

The immune system plays a critical role in inflammation by initiating responses to infections or tissue damage. The nuclear factor-κB (NF-κB) pathway plays a key role in inflammation and innate immunity, as well as other cellular activities. Dysregulation of this well-choreographed pathway has been implicated in various diseases, including cancer. CARD11 is a key molecule in the BCL10-MALT1 complex, which is involved in transducing the signal downstream of the NF-κB pathway. This study aims to elucidate how CARD11 overexpression exacerbates the prognosis of colorectal cancer (CRC). To identify the cellular pathways influenced by CARD11, transcriptomic analysis in both CRC cell lines and patients was carried out on CARD11- overexpressed HCT-116 and HT-29 CRC cell lines alongside empty vector-transfected cell lines. Furthermore, a comparison of transcriptomic data from adenoma and carcinoma CRC patients with low- (CARD11-) and high-(CARD11+) CARD11 expression was carried out. Whole transcriptomics and bioinformatics analysis results indicate that CARD11 appears to play a key role in CRC progression. Absolute GSEA (absGSEA) on HCT-116 transcriptomics data revealed that CARD11 overexpression promotes cell growth and tissue remodeling and enhances immune response. Key genes co-expressed with CARD11, such as EP300, KDM5A, HIF1A, NFKBIZ, and DUSP1, were identified as mediators of these processes. In the HT-29 cell line, CARD11 overexpression activated pathways involved in chemotaxis and extracellular matrix (ECM) organization, marked by IL1RN, MDK, SPP1, and chemokines like CXCL1, CXCL3, and CCL22, which were shown to contribute to the more invasive stage of CRC. In patient samples, adenoma patients exhibited increased expression of genes associated with the tumor immune microenvironment, such as IL6ST, collagen family members, and CRC transition markers, such as GLI3 and PIEZO2, in CARD11+ adenoma patients. Carcinoma patients showed a dramatic increase in the expression of MAPK8IP2 in CARD11+ carcinoma patients alongside other cancer-related genes, including EMB, EPHB6, and CPEB4.

PMID:39408697 | DOI:10.3390/ijms251910367

Int J Mol Sci. 2024 Sep 25;25(19):10329. doi: 10.3390/ijms251910329.

ABSTRACT

Fabry disease (FD) is an X-linked lysosomal disease whose ultimate consequences are the accumulation of sphingolipids and subsequent inflammatory events, mainly at the endothelial level. The outcomes include different nervous system manifestations as well as multiple organ damage. Despite the availability of known biomarkers, early detection of FD remains a medical need. This study aimed to develop an in silico model based on machine learning to identify candidate vascular and nervous system proteins for early FD damage detection at the cellular level. A combined systems biology and machine learning approach was carried out considering molecular characteristics of FD to create a computational model of vascular and nervous system disease. A data science strategy was applied to identify risk classifiers by using 10 K-fold cross-validation. Further biological and clinical criteria were used to prioritize the most promising candidates, resulting in the identification of 36 biomarker candidates with classifier abilities, which are easily measurable in body fluids. Among them, we propose four candidates, CAMK2A, ILK, LMNA, and KHSRP, which have high classification capabilities according to our models (cross-validated accuracy ≥ 90%) and are related to the vascular and nervous systems. These biomarkers show promise as high-risk cellular and tissue damage indicators that are potentially applicable in clinical settings, although in vivo validation is still needed.

PMID:39408658 | DOI:10.3390/ijms251910329

Int J Mol Sci. 2024 Sep 24;25(19):10287. doi: 10.3390/ijms251910287.

ABSTRACT

The serotonin 5-HT6 receptor (5-HT6R), expressed almost exclusively in the brain, affects the Cdk5 signaling as well as the mTOR pathway. Due to the association of 5-HT6R signaling with pathways involved in cancer progression, we decided to check the usefulness of 5-HT6R ligands in the treatment of CNS tumors. For this purpose, a new group of low-base 5-HT6R ligands was developed, belonging to arylsulfonamide derivatives of cyclic arylguanidines. The selected group of molecules was also tested for their antiproliferative activity on astrocytoma (1321N1) and glioblastoma (U87MG, LN-229, U-251) cell lines. Some of the molecules were subjected to ADMET tests in vitro, including lipophilicity, drug binding to plasma proteins, affinity for phospholipids, drug-drug interaction (DDI), the penetration of the membrane (PAMPA), metabolic stability, and hepatotoxicity as well as in vivo cardiotoxicity in the Danio rerio model. Two antagonists with an affinity constant Ki < 50 nM (PR 68Ki = 37 nM) were selected. These compounds were characterized by very high selectivity. An analysis of pharmacokinetic parameters for the lead compound PR 68 confirmed favorable properties for administration, including passive diffusion and acceptable metabolic stability (metabolized in 49%, MLMs). The compound did not exhibit the potential for drug-drug interactions.

PMID:39408617 | DOI:10.3390/ijms251910287

Biotechnol Biofuels Bioprod. 2024 Oct 15;17(1):128. doi: 10.1186/s13068-024-02572-8.

ABSTRACT

BACKGROUND: Lignin is an aromatic polymer deposited in secondary cell walls of higher plants to provide strength, rigidity, and hydrophobicity to vascular tissues. Due to its interconnections with cell wall polysaccharides, lignin plays important roles during plant growth and defense, but also has a negative impact on industrial processes aimed at obtaining monosaccharides from plant biomass. Engineering lignin offers a solution to this issue. For example, previous work showed that heterologous expression of a coliphage S-adenosylmethionine hydrolase (AdoMetase) was an effective approach to reduce lignin in the model plant Arabidopsis. The efficacy of this engineering strategy remains to be evaluated in bioenergy crops.

RESULTS: We studied the impact of expressing AdoMetase on lignin synthesis in sorghum (Sorghum bicolor L. Moench). Lignin content, monomer composition, and size, as well as biomass saccharification efficiency were determined in transgenic sorghum lines. The transcriptome and metabolome were analyzed in stems at three developmental stages. Plant growth and biomass composition was further evaluated under field conditions. Results evidenced that lignin was reduced by 18% in the best transgenic line, presumably due to reduced activity of the S-adenosylmethionine-dependent O-methyltransferases involved in lignin synthesis. The modified sorghum features altered lignin monomer composition and increased lignin molecular weights. The degree of methylation of glucuronic acid on xylan was reduced. These changes enabled a ~20% increase in glucose yield after biomass pretreatment and saccharification compared to wild type. RNA-seq and untargeted metabolomic analyses evidenced some pleiotropic effects associated with AdoMetase expression. The transgenic sorghum showed developmental delay and reduced biomass yields at harvest, especially under field growing conditions.

CONCLUSIONS: The expression of AdoMetase represents an effective lignin engineering approach in sorghum. However, considering that this strategy potentially impacts multiple S-adenosylmethionine-dependent methyltransferases, adequate promoters for fine-tuning AdoMetase expression will be needed to mitigate yield penalty.

PMID:39407217 | DOI:10.1186/s13068-024-02572-8

Nat Metab. 2024 Oct 15. doi: 10.1038/s42255-024-01146-0. Online ahead of print.

NO ABSTRACT

PMID:39406968 | DOI:10.1038/s42255-024-01146-0

Nat Neurosci. 2024 Oct 15. doi: 10.1038/s41593-024-01764-7. Online ahead of print.

ABSTRACT

Human microglia play a pivotal role in neurological diseases, but we still have an incomplete understanding of microglial heterogeneity, which limits the development of targeted therapies directly modulating their state or function. Here, we use single-cell RNA sequencing to profile 215,680 live human microglia from 74 donors across diverse neurological diseases and CNS regions. We observe a central divide between oxidative and heterocyclic metabolism and identify microglial subsets associated with antigen presentation, motility and proliferation. Specific subsets are enriched in susceptibility genes for neurodegenerative diseases or the disease-associated microglial signature. We validate subtypes in situ with an RNAscope-immunofluorescence pipeline and high-dimensional MERFISH. We also leverage our dataset as a classification resource, finding that induced pluripotent stem cell model systems capture substantial in vivo heterogeneity. Finally, we identify and validate compounds that recapitulate certain subtypes in vitro, including camptothecin, which downregulates the signature of disease-enriched subtypes and upregulates a signature previously associated with Alzheimer's disease.

PMID:39406950 | DOI:10.1038/s41593-024-01764-7

Nat Cancer. 2024 Oct 15. doi: 10.1038/s43018-024-00840-y. Online ahead of print.

ABSTRACT

Although the development of multiple primary tumors in smokers with lung cancer can be attributed to carcinogen-induced field cancerization, the occurrence of multiple tumors at presentation in individuals with EGFR-mutant lung cancer who lack known environmental exposures remains unexplained. In the present study, we identified ten patients with early stage, resectable, non-small cell lung cancer who presented with multiple, anatomically distinct, EGFR-mutant tumors. We analyzed the phylogenetic relationships among multiple tumors from each patient using whole-exome sequencing (WES) and hypermutable poly(guanine) (poly(G)) repeat genotyping as orthogonal methods for lineage tracing. In four patients, developmental mosaicism, assessed by WES and poly(G) lineage tracing, indicates a common non-germline cell of origin. In two other patients, we identified germline EGFR variants, which confer moderately enhanced signaling when modeled in vitro. Thus, in addition to germline variants, developmental mosaicism defines a distinct mechanism of genetic predisposition to multiple EGFR-mutant primary tumors, with implications for their etiology and clinical management.

PMID:39406916 | DOI:10.1038/s43018-024-00840-y

Nat Plants. 2024 Oct 15. doi: 10.1038/s41477-024-01818-5. Online ahead of print.

NO ABSTRACT

PMID:39406861 | DOI:10.1038/s41477-024-01818-5

Nat Commun. 2024 Oct 15;15(1):8883. doi: 10.1038/s41467-024-53288-0.

NO ABSTRACT

PMID:39406777 | DOI:10.1038/s41467-024-53288-0

Sci Rep. 2024 Oct 15;14(1):24191. doi: 10.1038/s41598-024-74192-z.

ABSTRACT

Ovarian germ cell tumors (OVGCTs) account for 28% of all diagnosed ovarian cancers, and malignant germ cell tumors specifically account for approximately 13% of diagnosed ovarian cancers in Saudi Arabia. Although most germ cell tumor patients have a high survival rate, patients who experience tumor recurrence have a poor prognosis and present with more aggressive and chemoresistant tumors. The use of immunotherapeutic agents such as PD-L1/PD-1 inhibitors for OVGCTs remains very limited because few studies have described the immunological characteristics of these tumors. This study is the first to investigate PD-L1 expression in ovarian germ cell tumors and explore the role of PD-L1 expression in tumor microenvironment cells and genetic alterations. A total of 34 ovarian germ cell tumors were collected from pathology archives. The collected tumor tissues included ten dysgerminomas, five yolk sac tumors, five immature teratomas, and one mature teratoma, and the remaining samples were mixed germ cell tumors. The tumors were analyzed using immunohistochemical analysis to determine PD-L1 expression, immune cell infiltration and cancer stem cell populations and their correlation with clinical outcome. Furthermore, the genetic alterations in different subtypes of germ cell tumors were correlated with PD-L1 expression and clinical outcome. Datasets for testicular germ cells (TGCTs) were retrieved from The Cancer Genome Atlas (TCGA) and analyzed using cBioPortal (cbioportal.org) and Gene Expression Profiling Interactive Analysis (GEPIA). Compared with yolk sac tumors, dysgerminomas highly express PD-L1 and are associated with high levels of tumor infiltrating lymphocytes (TILs) and stem cell markers. In addition, compared with PD-L1-negative yolk sac tissue, dysgerminomas/seminomas with high PD-L1 expression are associated with more genetic alterations and a better prognosis. Our findings will contribute to the knowledge about the potential benefits of ovarian cancer immunotherapy in specific subsets of germ cell tumor patients and the risk factors for resistance mediated by tumor microenvironment cells.

PMID:39406772 | DOI:10.1038/s41598-024-74192-z

Am J Hum Genet. 2024 Oct 10:S0002-9297(24)00365-3. doi: 10.1016/j.ajhg.2024.09.005. Online ahead of print.

ABSTRACT

A recent publication describing the assembly of the Y chromosomes of 43 males was remarkable not only for its ambitious technical scope but also for the startling suggestion that the boundary of the pseudoautosomal region 1 (PAR1), where the human X and Y chromosomes engage in crossing-over during male meiosis, lies 500 kb distal to its previously reported location. Where is the boundary of the human PAR1? We first review the evidence that mapped the PAR boundary, or PAB, before the human genome draft sequence was produced, then examine post-genomic datasets for evidence of crossing-over between the X and Y, and lastly re-examine contiguous sequence assemblies of the PAR-NPY boundary to see whether they support a more distal PAB. We find ample evidence of X-Y crossovers throughout the 500 kb in question, some as close as 246 bp to the previously reported PAB. Our new analyses, combined with previous studies over the past 40 years, provide overwhelming evidence to support the original position and narrow the probable location of the PAB to a 201-bp window.

PMID:39406244 | DOI:10.1016/j.ajhg.2024.09.005

Neuron. 2024 Oct 12:S0896-6273(24)00662-7. doi: 10.1016/j.neuron.2024.09.014. Online ahead of print.

ABSTRACT

Repetitive use of morphine (MF) and other opioids can trigger two major pain-related side effects: opioid-induced hypersensitivity (OIH) and analgesic tolerance, which can be subclassified as mechanical and thermal. The central mechanisms underlying mechanical OIH/tolerance remain unresolved. Here, we report that a brain-to-spinal opioid pathway, starting from μ-opioid receptor (MOR)-expressing neuron in the lateral parabrachial nucleus (lPBNMOR+) via dynorphin (Dyn) neuron in the paraventricular hypothalamic nucleus (PVHDyn+) to κ-opioid receptor (KOR)-expressing GABAergic neuron in the spinal dorsal horn (SDHKOR-GABA), controls repeated systemic administration of MF-induced mechanical OIH and tolerance in mice. The above effect is likely mediated by disruption of dorsal horn gate control for MF-resistant mechanical pain via silencing of the Dyn-positive GABAergic neurons in the SDH (lPBNMOR+ → PVHDyn+ → SDHKOR-GABA → SDHDyn-GABA). Repetitive binding of MF to MORs during repeated MF administration disrupted the above circuits. Targeting the above brain-to-spinal opioid pathways rescued repetitive MF-induced mechanical OIH and tolerance.

PMID:39406237 | DOI:10.1016/j.neuron.2024.09.014

Cell Genom. 2024 Oct 10:100672. doi: 10.1016/j.xgen.2024.100672. Online ahead of print.

ABSTRACT

A single gene may have multiple enhancers, but how they work in concert to regulate transcription is poorly understood. To analyze enhancer interactions throughout the genome, we developed a generalized linear modeling framework, GLiMMIRS, for interrogating enhancer effects from single-cell CRISPR experiments. We applied GLiMMIRS to a published dataset and tested for interactions between 46,166 enhancer pairs and corresponding genes, including 264 "high-confidence" enhancer pairs. We found that enhancer effects combine multiplicatively but with limited evidence for further interactions. Only 31 enhancer pairs exhibited significant interactions (false discovery rate <0.1), none of which came from the high-confidence set, and 20 were driven by outlier expression values. Additional analyses of a second CRISPR dataset and in silico enhancer perturbations with Enformer both support a multiplicative model of enhancer effects without interactions. Altogether, our results indicate that enhancer interactions are uncommon or have small effects that are difficult to detect.

PMID:39406234 | DOI:10.1016/j.xgen.2024.100672

Cell Rep Methods. 2024 Oct 9:100877. doi: 10.1016/j.crmeth.2024.100877. Online ahead of print.

ABSTRACT

The fragmentation patterns of cell-free DNA (cfDNA) in plasma can potentially be utilized as diagnostic biomarkers in liquid biopsy. However, our knowledge of this biological process and the information encoded in fragmentation patterns remains preliminary. Here, we investigated the cfDNA fragmentomic characteristics against nucleosome positioning patterns in hematopoietic cells. cfDNA molecules with ends located within nucleosomes were relatively shorter with altered end motif patterns, demonstrating the feasibility of enriching tumor-derived cfDNA in patients with cancer through the selection of molecules possessing such ends. We then developed three cfDNA fragmentomic metrics after end selection, which showed significant alterations in patients with cancer and enabled cancer diagnosis. By incorporating machine learning, we further built high-performance diagnostic models, which achieved an overall area under the curve of 0.95 and 85.1% sensitivity at 95% specificity. Hence, our investigations explored the end characteristics of cfDNA fragmentomics and their merits in building accurate and sensitive cancer diagnostic models.

PMID:39406232 | DOI:10.1016/j.crmeth.2024.100877