Robustness of cancer microbiome signals over a broad range of methodological variation

Oncogene, Journal Year: 2024, Volume and Issue: 43(15), P. 1127 - 1148

Published: Feb. 23, 2024

Abstract In 2020, we identified cancer-specific microbial signals in The Cancer Genome Atlas (TCGA) [1]. Multiple peer-reviewed papers independently verified or extended our findings [2–12]. Given this impact, carefully considered concerns by Gihawi et al. [13] that batch correction and database contamination with host sequences artificially created the appearance of cancer type-specific microbiomes. (1) We tested comparing raw Voom-SNM-corrected data per-batch, finding predictive equivalence significantly similar features. found consistent results a modern microbiome-specific method (ConQuR [14]), when restricting to taxa an independent, highly-decontaminated cohort. (2) Using Conterminator [15], low levels human original databases (~1% genomes). demonstrated increased detection reads was due using newer genome reference. (3) developed Exhaustive, twice as sensitive Conterminator, clean RefSeq. comprehensively host-deplete TCGA many (pan)genome references. repeated all analyses pipeline, These extensive re-analyses updated methods validate conclusion signatures exist TCGA, show they are robust methodology.

Language: Английский

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The mysterious anelloviruses: investigating its role in human diseases

BMC Microbiology, Journal Year: 2024, Volume and Issue: 24(1)

Published: Jan. 29, 2024

Abstract Anelloviruses (AVs) that infect the human population are members of Anelloviridae family. They widely distributed in populations worldwide. Torque teno virus (TTV) was first this family to be identified and is estimated found serum 80–90% population. Sometime after identification TTV, mini (TTMV) midi (TTMDV) were also classified Since identifying these viruses, have been detected various types biological fluids body, including blood urine, as well vital organs such liver kidney. can transmitted from person through transfusions, fecal-oral contact, possibly sexual intercourse. Recent studies on newly introduced viruses show although they not directly related disease, may indirectly involved initiating or exacerbating some population-related diseases viral infections. Among diseases, we mention cancers, immune system infections, hepatitis, AIDS. Also, likely use microRNAs (miRNAs) encode fulfill cooperative role. recent years, role proliferation their load, especially has highlighted indicate status immunocompromised people who undergo organ transplants. Here, review possible target humans highlight them important require further study. This provide new insights researchers.

Language: Английский

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Cancer type classification using plasma cell-free RNAs derived from human and microbes

eLife, Journal Year: 2022, Volume and Issue: 11

Published: July 11, 2022

The utility of cell-free nucleic acids in monitoring cancer has been recognized by both scientists and clinicians. In addition to human transcripts, a fraction plasma were proven be derived from microbes reported have relevance cancer. To obtain better understanding RNAs (cfRNAs) patients, we profiled cfRNAs ~300 samples 5 types (colorectal cancer, stomach liver lung esophageal cancer) healthy donors (HDs) with RNA-seq. Microbe-derived consistently detected different computational methods when potential contaminations carefully filtered. Clinically relevant signals identified microbial reads, enriched Kyoto Encyclopedia Genes Genomes pathways downregulated genes higher prevalence torque teno viruses suggest that patients immunosuppressed. Our data support the diagnostic value microbe-derived for detection, as an area under ROC curve approximately 0.9 distinguishing HDs was achieved. Moreover, type specificity, combining two features could distinguish tumors five primary locations average recall 60.4%. Compared using alone, adding improved 8%. summary, this work provides evidence clinical their utilities detection well determination tumor sites.

Language: Английский

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Cell-free multi-omics analysis reveals potential biomarkers in gastrointestinal cancer patients’ blood

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(11), P. 101281 - 101281

Published: Nov. 1, 2023

During cancer progression, tumorigenic and immune signals are spread through circulating molecules, such as cell-free DNA (cfDNA) RNA (cfRNA) in the blood. So far, they have not been comprehensively investigated gastrointestinal cancers. Here, we profile 4 categories of omics data from patients with colorectal stomach adenocarcinoma then assay 15 types genomic, epigenomic, transcriptomic variations. We find that multi-omics more appropriate for detection genes compared single-omics data. In particular, cfRNAs sensitive informative than cfDNAs terms rate, enriched functional pathways, etc. Moreover, identify several peripheral signatures suppressed cancer. Specifically, establish a γδ-T cell score cancer-associated-fibroblast (CAF) score, providing insights into clinical statuses like stage survival. Overall, reveal multi-molecular landscape is useful blood monitoring personalized treatment.

Language: Английский

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An ultrasensitive method for detection of cell-free RNA

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Language: Английский

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Profiling of repetitive RNA sequences in the blood plasma of patients with cancer

Nature Biomedical Engineering, Journal Year: 2023, Volume and Issue: 7(12), P. 1627 - 1635

Published: Aug. 31, 2023

Abstract Liquid biopsies provide a means for the profiling of cell-free RNAs secreted by cells throughout body. Although well-annotated coding and non-coding transcripts in blood are readily detectable can serve as biomarkers disease, overall diagnostic utility transcriptome remains unclear. Here we show that derived from transposable elements other repeat enriched patients with cancer, they signatures accurate classification disease. We used repeat-element-aware liquid-biopsy technology single-molecule nanopore sequencing to profile plasma cancer examine millions genomic features comprising all annotated genes genome. By aggregating individual subfamily level, found samples pancreatic specific Alu subfamilies, whereas cancers have their own characteristic RNA profile. Our findings repetitive sequences abundant be disease-specific biomarkers.

Language: Английский

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Liquid Biopsy in Lung Cancer: Biomarkers for the Management of Recurrence and Metastasis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8894 - 8894

Published: May 17, 2023

Liquid biopsies have emerged as a promising tool for the detection of metastases well local and regional recurrence in lung cancer. biopsy tests involve analyzing patient’s blood, urine, or other body fluids biomarkers, including circulating tumor cells tumor-derived DNA/RNA that been shed into bloodstream. Studies shown liquid can detect cancer with high accuracy sensitivity, even before they are visible on imaging scans. Such valuable early intervention personalized treatment, aiming to improve patient outcomes. also minimally invasive compared traditional tissue biopsies, which require removal sample further analysis. This makes more convenient less risky option patients, particularly those who not good candidates procedures due medical conditions. While relapse still being developed validated, hold great promise improving treatment this deadly disease. Herein, we summarize available novel approaches describe their applications clinical practice.

Language: Английский

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Cell-free circulating tumor RNAs in plasma as the potential prognostic biomarkers in colorectal cancer

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: April 5, 2023

Background Cell free RNA (cfRNA) contains transcript fragments from multiple cell types, making it useful for cancer detection in clinical settings. However, the pathophysiological origins of cfRNAs plasma colorectal (CRC) patients remain unclear. Methods To identify tissue-specific contributions transcriptomic profile, we used a published single-cell transcriptomics profile to deconvolute type abundance among paired samples CRC who underwent tumor-ablative surgery. We further validated differentially expressed 5 pairs tumor and adjacent tissue as well 3 additional using RNA-sequencing. Results The component intestinal secretory cells was significantly decreased in-house post-surgical cfRNA. HPGD , PACS1 TDP2 expression consistent across cfRNA samples. Using Cancer Genome Atlas (TCGA) datasets, were able classify into two groups with different survival outcomes. Conclusions three-gene signature holds promise applying minimal residual disease (MRD) testing, which involves profiling remnants after or during treatment. Biomarkers identified present study need be larger cohort order ascertain their possible use early diagnosis CRC.

Language: Английский

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Circulating cell-free DNA-based multi-cancer early detection

Trends in cancer, Journal Year: 2023, Volume and Issue: 10(2), P. 161 - 174

Published: Sept. 14, 2023

Language: Английский

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Pathformer: a biological pathway informed transformer for disease diagnosis and prognosis using multi-omics data

Bioinformatics, Journal Year: 2024, Volume and Issue: 40(5)

Published: May 1, 2024

Abstract Motivation Multi-omics data provide a comprehensive view of gene regulation at multiple levels, which is helpful in achieving accurate diagnosis complex diseases like cancer. However, conventional integration methods rarely utilize prior biological knowledge and lack interpretability. Results To integrate various multi-omics tissue liquid biopsies for disease prognosis, we developed pathway informed Transformer, Pathformer. It embeds input with compacted multi-modal vector pathway-based sparse neural network. Pathformer also leverages criss-cross attention mechanism to capture the crosstalk between different pathways modalities. We first benchmarked 18 comparable on cancer datasets, where outperformed all other methods, an average improvement 6.3%–14.7% F1 score survival prediction, 5.1%–12% stage 8.1%–13.6% drug response prediction. Subsequently, prognosis prediction based data, used case study demonstrate interpretability by identifying key their crosstalk. Then, early biopsy plasma platelet datasets Pathformer’s potential clinical applications screening. Moreover, revealed deregulation interesting (e.g. scavenger receptor pathway) patients’ blood, providing candidate targets microenvironment study. Availability implementation implemented freely available https://github.com/lulab/Pathformer.

Language: Английский

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