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| Open AccessTumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis
‘Circulating cell-free DNA can be used to predict cancer, but it is more challenging to assess in early stage cancer. Here, the authors created a diagnostic model using tumor fractions deciphered from circulating cfDNA methylation signatures, which exhibited an 86% sensitivity in detecting early-stage cancer.
- Xiao Zhou
- , Zhen Cheng
- & Weibin Cheng
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Article
| Open AccessAn umbrella review of the evidence linking oral health and systemic noncommunicable diseases
Previous studies have supported a potential bidirectional association between oral diseases and systemic noncommunicable diseases (NCDs) Here the authors perform an umbrella review of meta-analyses for the association between oral health and NCDs, and report that 27 NCDs were associated with oral disease, however, the overall strength of evidence was found to be unfavorable and with methodological inconsistencies.
- João Botelho
- , Paulo Mascarenhas
- & Vanessa Machado
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Article
| Open AccessA framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA
Nucleosome profiling from cell-free DNA (cfDNA) represents a potential approach for cancer detection and classification. Here, the authors develop Griffin, a computational framework for tumour subtype classification based on cfDNA nucleosome profiling that can work with ultra-low pass sequencing data.
- Anna-Lisa Doebley
- , Minjeong Ko
- & Gavin Ha
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Article
| Open AccessNasal DNA methylation at three CpG sites predicts childhood allergic disease
Accurate prediction of the onset of childhood allergy is important to clarify the difference between various respiratory diseases. Here the authors propose that the methylation status of three sites in nasal DNA predicts the onset of childhood allergy which may aid diagnosis and monitoring.
- Merlijn van Breugel
- , Cancan Qi
- & Cheng-Jian Xu
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Article
| Open AccessA self-powered ingestible wireless biosensing system for real-time in situ monitoring of gastrointestinal tract metabolites
Metabolic dynamics within the small intestine are difficult to study due to the lack of in situ access. Here, the authors report an ingestible, self-powered, and wireless biosensing system, demonstrating proof-of-principle real-time glucose monitoring in the small intestines of pigs.
- Ernesto De la Paz
- , Nikhil Harsha Maganti
- & Patrick P. Mercier
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Article
| Open AccessA click chemistry amplified nanopore assay for ultrasensitive quantification of HIV-1 p24 antigen in clinical samples
Accurate detection of antigen p24 for HIV−1 early diagnosis remains challenging. Here the authors present a click chemistry amplified nanopore (CAN) assay that allows p24 quantification at ultralow concentration range in clinical samples.
- Xiaojun Wei
- , Xiaoqin Wang
- & Chang Liu
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Article
| Open AccessFaecal microbiome-based machine learning for multi-class disease diagnosis
Here, using fecal metagenomics data of 2,320 individuals, the authors develop a microbiome-based machine learning approach showing high accuracy for multi-class disease diagnosis, highlighting its potential application in improving noninvasive diagnostics and monitor responses to therapy.
- Qi Su
- , Qin Liu
- & Siew C. Ng
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Article
| Open AccessMeasurements of heterogeneity in proteomics analysis of the nanoparticle protein corona across core facilities
Analysis of the protein corona formed around nanoparticles is important for multiple applications in nanomedicine, the methods used at core facilities used for analysis can impact the results. Here, the authors report on a study into the variability of the results obtained from 17 different core facilities and the implications of this.
- Ali Akbar Ashkarran
- , Hassan Gharibi
- & Morteza Mahmoudi
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Article
| Open AccessUltrafast one-minute electronic detection of SARS-CoV-2 infection by 3CLpro enzymatic activity in untreated saliva samples
Methods for the detection of active viral infection are desirable. Here, the authors report an electrochemical approach targeting a SARS-CoV-2 proteolytic enzyme called 3CLpro, as a marker of active infection.
- Ella Borberg
- , Eran Granot
- & Fernando Patolsky
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Article
| Open AccessStratifin as a novel diagnostic biomarker in serum for diffuse alveolar damage
No reliable serum biomarker for diffuse alveolar damage, a poor prognosis subtype of drug-induced interstitial lung disease, is currently available. Here, the authors show stratifin/14-3-3σ in serum is a promising biomarker for diagnosis of this type of disease.
- Noriaki Arakawa
- , Atsuhito Ushiki
- & Masayuki Hanaoka
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Article
| Open AccessAdversarial attacks and adversarial robustness in computational pathology
Artificial Intelligence can support diagnostic workflows in oncology, but they are vulnerable to adversarial attacks. Here, the authors show that convolutional neural networks are highly susceptible to white- and black-box adversarial attacks in clinically relevant classification tasks.
- Narmin Ghaffari Laleh
- , Daniel Truhn
- & Jakob Nikolas Kather
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Article
| Open AccessCost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer
Early cancer detection by cell-free DNA (cfDNA) is challenged by the low amount of tumour DNA in cfDNA, tumour heterogeneity and the small patient cohorts. Here, the authors develop a method, cfMethyl-Seq, for cost-effective methylome profiling of cfDNA and for detecting and locating cancer.
- Mary L. Stackpole
- , Weihua Zeng
- & Xianghong Jasmine Zhou
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Article
| Open AccessThe complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure
Right ventricular (RV) failure is clinically crucial, but there is no specific therapy. Here, the authors show that the complement alternative pathway is activated in RV failure and that blockade of the pathway ameliorates RV failure in mice.
- Shogo Ito
- , Hisayuki Hashimoto
- & Shinsuke Yuasa
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Article
| Open AccessIdentifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes
Genetic association studies for rare variants suffer from lack of power and thus there is a need for methods to improve rare variant discovery. Here, the authors present functionally informed association tests with increased statistical power to aid discovery and interpretation of rare variants.
- Remo Monti
- , Pia Rautenstrauch
- & Christoph Lippert
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Article
| Open AccessReversal of the renal hyperglycemic memory in diabetic kidney disease by targeting sustained tubular p21 expression
Persistent diabetic complications despite controlled blood glucose levels, known as hyperglycemic memory, remain a poorly understood phenomenon in diabetic kidney disease. Here the authors identify senescence-associated gene p21 as a regulator of hyperglycemic memory, the suppression of which improves hyperglycemic memory and renal function.
- Moh’d Mohanad Al-Dabet
- , Khurrum Shahzad
- & Berend Isermann
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Article
| Open AccessGenome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA
Detection of mutational signatures in cell-free DNA (cfDNA) is challenging due to low sequence coverage and low mutant allele fractions. Here, the authors identify mutational signatures in plasma whole genome sequencing of cancer patients and use machine learning to distinguish them from healthy individuals.
- Jonathan C. M. Wan
- , Dennis Stephens
- & Luis A. Diaz Jr.
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Article
| Open AccessDerivation and utility of schizophrenia polygenic risk associated multimodal MRI frontotemporal network
Schizophrenia is highly heritable and characterized by widespread brain abnormalities. Here, the authors identify schizophrenia polygenic risk associated multimodal frontotemporal network that can serve as a transdiagnostic brain signature specific to schizophrenia.
- Shile Qi
- , Jing Sui
- & Vince D. Calhoun
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Article
| Open AccessCross-tissue analysis of blood and brain epigenome-wide association studies in Alzheimer’s disease
DNA methylation differences in Alzheimer’s disease have been previously reported, although the interpretation of the differences is unclear. Here, the authors performed epigenome-wide meta-analyses of DNA methylation in blood and brain, and developed a methylation-based risk prediction model for AD.
- Tiago C. Silva
- , Juan I. Young
- & Lily Wang
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Article
| Open AccessLandscape of somatic alterations in large-scale solid tumors from an Asian population
Understanding the mutation landscape of cancer may enable the development of more targeted therapies. Here, the authors sequence a panel of genes in a large Asian cohort and compare to American cohorts and find 64% of the Asian patients have actionable mutations.
- Liqun Wu
- , Herui Yao
- & Minghui Wang
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Article
| Open AccessEmergency triage of brain computed tomography via anomaly detection with a deep generative model
Triage is essential for the early diagnosis and reporting of emergency patients in the emergency department. Here, the authors develop an anomaly detection algorithm with a deep generative model that reprioritizes radiology worklists and provides lesion attention maps for brain CT images with critical findings.
- Seungjun Lee
- , Boryeong Jeong
- & Namkug Kim
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Article
| Open Access[11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer’s disease
The link between amyloid and tau proteins with Alzheimer’s disease progression remains unclear. Here, the authors propose HDACs I downregulation as an element linking the deleterious effects of brain proteinopathies with disease progression.
- Tharick A. Pascoal
- , Mira Chamoun
- & Pedro Rosa-Neto
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Matters Arising
| Open AccessReply to: Limitations of molecular testing in combination with computerized tomographic for lung cancer screening
- Dimitrios Mathios
- , Peter B. Bach
- & Victor E. Velculescu
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Article
| Open AccessThe impact of malaria-protective red blood cell polymorphisms on parasite biomass in children with severe Plasmodium falciparum malaria
Numerous candidate malaria protective gene polymorphisms have been proposed. Here, Uyoga et al. investigate associations between malaria-protective red blood cell polymorphisms and total parasite biomass estimated from plasma concentrations of PfHRP2, in a cohort of Kenyan children suffering from severe malaria. They suggest that plasma PfHRP2 and the ratio of the plasma PfHRP2 to the peripheral parasite density (sequestration index) as powerful quantitative phenotypic traits for severe malaria.
- S. Uyoga
- , J. A. Watson
- & T. N. Williams
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Article
| Open AccessADAMTS4-specific MR probe to assess aortic aneurysms in vivo using synthetic peptide libraries
New biomarkers are required to improve the assessment of aortic wall integrity and risk of rupture. Here the authors report the development of an imaging probe for ADAMTS4, which they test in an abdominal aortic aneurysm mouse model and show in vivo prediction of aneurysm and rupture.
- Jan O. Kaufmann
- , Julia Brangsch
- & Marcus R. Makowski
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Article
| Open AccessNoninvasive urinary protein signatures associated with colorectal cancer diagnosis and metastasis
More sensitive and specific non-invasive biomarkers are desired for early detection of cancer. Here, the authors show a protein signature in the urine that increases sensitivity for colorectal cancer detection when combined with fecal immunochemical tests and corrects diagnosis in some fecal immunochemical tests-negative patients.
- Yulin Sun
- , Zhengguang Guo
- & Xiaohang Zhao
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Article
| Open AccessAn efficient urine peptidomics workflow identifies chemically defined dietary gluten peptides from patients with celiac disease
Gluten peptides from wheat enter the bloodstream and are excreted in urine but are yet to be chemically characterised. Here, the authors show by mass spectrometry that quantitative and qualitative differences in urinary peptides can be detected between healthy people and patients with celiac disease.
- Brad A. Palanski
- , Nielson Weng
- & Joshua E. Elias
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Article
| Open AccessGut metagenome associations with extensive digital health data in a volunteer-based Estonian microbiome cohort
Here, the authors present results of the Estonian Microbiome Project, which combines metagenomics and electronic health data from 2500 individuals, expanding microbiome-host interactions in particular with regards to effects of long-term antibiotic usage on the microbiome across diseases.
- Oliver Aasmets
- , Kertu Liis Krigul
- & Elin Org
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Article
| Open AccessSmart facemask for wireless CO2 monitoring
While facemasks are recommended to prevent the spread of SARS-CoV-2, potential adverse effects may occur upon prolonged usage. Here the authors develop and evaluate an opto-chemical sensor incorporated into a smart FFP2-type facemask for wireless, real-time CO2 monitoring.
- P. Escobedo
- , M. D. Fernández-Ramos
- & A. J. Palma
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Article
| Open AccessVascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue
The vascular, cellular and molecular changes underlying sex differences in mood disorders are unclear. Here, the authors show that blood-brain barrier dysfunction modulates anxiety- and depressive-like behaviors in female mice and endothelium-specific changes associated with maladaptive responses compared to resilience to stress.
- Laurence Dion-Albert
- , Alice Cadoret
- & Caroline Menard
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Article
| Open AccessLipidomic profiling of human serum enables detection of pancreatic cancer
Patients with pancreatic cancer have a poor prognosis, more research is required to identify the disease at an earlier stage. Here, the authors use lipid profiles of blood samples and show that they can distinguish patients with pancreatic cancer from healthy controls.
- Denise Wolrab
- , Robert Jirásko
- & Michal Holčapek
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Article
| Open AccessMassive image-based single-cell profiling reveals high levels of circulating platelet aggregates in patients with COVID-19
The authors report the landscape of circulating platelet aggregates in COVID-19 obtained by massive single-cell image-based profiling and temporal monitoring to elucidate the underlying process of COVID-19-assocaited microvascular thrombosis.
- Masako Nishikawa
- , Hiroshi Kanno
- & Keisuke Goda
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Article
| Open AccessSARS-CoV-2 antibody seroprevalence and associated risk factors in an urban district in Cameroon
Many African countries have reported relatively low numbers of COVID-19 cases but the true scale of the epidemic is unclear. Here, the authors conduct a population-based survey in a province of Cameroon and estimate 29% seroprevlance, >300 fold higher than the nationwide attack rate implied by case counts.
- Kene Nwosu
- , Joseph Fokam
- & Laura Ciaffi
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Article
| Open AccessIdentification of the factor XII contact activation site enables sensitive coagulation diagnostics
Blood coagulation is started by contact to surfaces and this is the principle for a commonly used diagnostic clotting test, aPTT. Here, the authors identify the structure in coagulation factor XII that initiates surface-driven coagulation and use the information to develop improved aPTT assays.
- Marco Heestermans
- , Clément Naudin
- & Thomas Renné
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Article
| Open AccessAutomatic detection of 39 fundus diseases and conditions in retinal photographs using deep neural networks
Systems for automatic detection of a single disease may miss other important conditions. Here, the authors show a deep learning platform can detect 39 common retinal diseases and conditions.
- Ling-Ping Cen
- , Jie Ji
- & Mingzhi Zhang
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Article
| Open AccessCirculating trophoblast cell clusters for early detection of placenta accreta spectrum disorders
Placenta accreta spectrum (PAS) is a high-risk obstetrical complication associated with significant morbidity and mortality. Here the authors discover a uniquely high prevalence of circulating trophoblasts clusters in PAS and explore their diagnostic potential to augment current diagnostic modalities for the early detection of PAS.
- Yalda Afshar
- , Jiantong Dong
- & Yazhen Zhu
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Article
| Open AccessThe impact of site-specific digital histology signatures on deep learning model accuracy and bias
Deep learning models have been trained on The Cancer Genome Atlas to predict numerous features directly from histology, including survival, gene expression patterns, and driver mutations. Here, the authors demonstrate that site-specific histologic signatures can lead to biased estimates of accuracy for such models, and propose a method to minimize such bias.
- Frederick M. Howard
- , James Dolezal
- & Alexander T. Pearson
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Article
| Open AccessMultianalyte serology in home-sampled blood enables an unbiased assessment of the immune response against SARS-CoV-2
Here, Roxhed et al. develop a multiplexed approach to screen IgG and IgM levels against several SARS-CoV-2 proteins in home-sampled dried blood spots and estimate seroprevalence of 12.5% in Stockholm in spring of 2020.
- Niclas Roxhed
- , Annika Bendes
- & Jochen M. Schwenk
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Article
| Open AccessA multicentre validation study of the diagnostic value of plasma neurofilament light
Cerebrospinal fluid neurofilament light (NfL) is a biomarker for neurodegeneration that can also be assessed in blood. Here the authors show in a validation study the potential for plasma NfL as a biomarker for several neurodegenerative diseases.
- Nicholas J. Ashton
- , Shorena Janelidze
- & Oskar Hansson
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Article
| Open AccessImaging-based spectrometer-less optofluidic biosensors based on dielectric metasurfaces for detecting extracellular vesicles
The authors engineer a type of bound states in the continuum in diatomic dielectric metasurfaces, allowing for high-quality resonances with accessible enhanced fields. Metasurface microarrays are integrated with microfluidics on an imaging platform for real-time detection of biosamples, based on reconstructing spectral shift information.
- Yasaman Jahani
- , Eduardo R. Arvelo
- & Hatice Altug
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Article
| Open AccessIdentification of microbial markers across populations in early detection of colorectal cancer
The gut microbiome plays an important role in colorectal carcinogenesis and predictive microbiome signatures have been proposed for colorectal cancer (CRC) diagnosis. Here the authors perform a meta-analysis of 16S rRNA-based profiles to identify microbial markers able to discriminate patients with adenoma from control and CRC, building a model that can be applied for the early detection of CRC.
- Yuanqi Wu
- , Na Jiao
- & Lixin Zhu
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Article
| Open AccessGene-level metagenomic architectures across diseases yield high-resolution microbiome diagnostic indicators
Here, combing the massive gene-universe of the gut microbiome to identify strain-specific, cross-disease, associations across seven human diseases, the authors introduce the concept of microbiome architecture, defined as the complete set of positive and negative associations between microbial genes and human host disease, highlighting microbiome architectures as potential diagnostic indicators.
- Braden T. Tierney
- , Yingxuan Tan
- & Chirag J. Patel
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Article
| Open AccessA machine learning model for identifying patients at risk for wild-type transthyretin amyloid cardiomyopathy
Transthyretin amyloid cardiomyopathy is a treatable but often unrecognized cause of heart failure. We derived and validated a machine learning model based on medical diagnostic codes that identifies heart failure patients at risk for wild-type transthyretin amyloid cardiomyopathy.
- Ahsan Huda
- , Adam Castaño
- & Sanjiv J. Shah
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Article
| Open AccessComprehensive cell type decomposition of circulating cell-free DNA with CelFiE
Tissue damage and turnover lead to the release of DNA in the blood and can be used to monitor changes in tissue state. Here, the authors developed a tool to accurately estimate the proportion of cell types contributing to cell-free DNA in the blood, with an application to pregnant women and ALS patients.
- Christa Caggiano
- , Barbara Celona
- & Noah Zaitlen
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Article
| Open AccessProtein analysis of extracellular vesicles to monitor and predict therapeutic response in metastatic breast cancer
A thermophoretic aptasensor can be used to profile cancer-associated proteins of extracellular vesicles (EVs) in patients’ plasma. Here, the authors use this technique to develop an EV-signature able to discriminate metastatic breast cancer, monitor treatment response, and predict patients’ progression-free survival.
- Fei Tian
- , Shaohua Zhang
- & Jiashu Sun
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Article
| Open AccessNext generation plasma proteome profiling to monitor health and disease
The proximity extension assay (PEA) is a popular tool to measure plasma protein levels. Here, the authors extend the proteome coverage of PEA by combining it with next-generation sequencing, enabling the analysis of nearly 1500 proteins from minute amounts of plasma.
- Wen Zhong
- , Fredrik Edfors
- & Mathias Uhlén
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Article
| Open AccessA haemagglutination test for rapid detection of antibodies to SARS-CoV-2
Serological detection of antibodies against SARS-CoV-2 can help establish rates of seroconversion. Here the authors develop a red cell agglutination test to detect antibodies against the receptor binding domain for distribution free of charge to qualified research groups.
- Alain Townsend
- , Pramila Rijal
- & Etienne Joly
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Article
| Open AccessN-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection
Here the authors develop a single molecule array (Simoa) immunoassay for detection of SARS-CoV-2 nucleocapsid protein in venous and dried capillary blood as well as saliva. The assay shows good performance in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals.
- Dandan Shan
- , Joseph M. Johnson
- & Andrew J. Ball
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Article
| Open AccessA wearable patch for continuous analysis of thermoregulatory sweat at rest
Low secretion rates and evaporation pose challenges for collecting resting thermoregulatory sweat for non-invasive analysis of body physiology. Here the authors present wearable microfluidics-based patches for continuous sweat monitoring at rest that enable detection of pH, Cl−, and levodopa for dynamic sweat analysis related to routine activities, stress events, hypoglycemia-induced sweating, and Parkinson’s disease.
- Hnin Yin Yin Nyein
- , Mallika Bariya
- & Ali Javey
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Article
| Open AccessA homogeneous split-luciferase assay for rapid and sensitive detection of anti-SARS CoV-2 antibodies
Serological tests are important diagnostic and disease surveillance tools for addressing the COVID-19 pandemic. Here, the authors present a tri-part Nanoluciferase based assay to detect antibodies against SARS-CoV-2.
- Zhong Yao
- , Luka Drecun
- & Igor Stagljar