Biomarkers

  • Article
    | Open Access

    α-Syn in CSF is a biomarker of neurodegenerative diseases; however, the detection of clinically relevant species is difficult. Here, the authors create a nanobody biosensor that reveals the presence of α-Syn in cells, which allow the detection of transmittable forms of α-Syn present in human CSF.

    • Christoph Gerdes
    • , Natalia Waal
    • , Thomas Offner
    • , Eugenio F. Fornasiero
    • , Nora Wender
    • , Hannes Verbarg
    • , Ivan Manzini
    • , Claudia Trenkwalder
    • , Brit Mollenhauer
    • , Timo Strohäker
    • , Markus Zweckstetter
    • , Stefan Becker
    • , Silvio O. Rizzoli
    • , Fitnat Buket Basmanav
    •  & Felipe Opazo
  • Article
    | Open Access

    Gut microbiome has been linked to cavernous angioma (CA), a common vascular disease, but the role in humans remains unclear. Here, the authors combine 16S rRNA sequencing and shotgun metagenomics to profile the microbiome in a large cohort of human subjects with and without CA, and among subjects with different CA clinical features.

    • Sean P. Polster
    • , Anukriti Sharma
    • , Ceylan Tanes
    • , Alan T. Tang
    • , Patricia Mericko
    • , Ying Cao
    • , Julián Carrión-Penagos
    • , Romuald Girard
    • , Janne Koskimäki
    • , Dongdong Zhang
    • , Agnieszka Stadnik
    • , Sharbel G. Romanos
    • , Seán B. Lyne
    • , Robert Shenkar
    • , Kimberly Yan
    • , Cornelia Lee
    • , Amy Akers
    • , Leslie Morrison
    • , Myranda Robinson
    • , Atif Zafar
    • , Kyle Bittinger
    • , Helen Kim
    • , Jack A. Gilbert
    • , Mark L. Kahn
    • , Le Shen
    •  & Issam A. Awad
  • Article
    | Open Access

    There are no reliable tests for placental insufficiency, which can lead to fetal growth restriction and stillbirth. Here the authors demonstrate that low levels of circulating SPINT1 are associated to low birthweight, and several ultrasound and neonatal anthropomorphic indicators of placental insufficiency.

    • Tu’uhevaha J. Kaitu’u-Lino
    • , Teresa M. MacDonald
    • , Ping Cannon
    • , Tuong-Vi Nguyen
    • , Richard J. Hiscock
    • , Nick Haan
    • , Jenny E. Myers
    • , Roxanne Hastie
    • , Kirsten M. Dane
    • , Anna L. Middleton
    • , Intissar Bittar
    • , Amanda N. Sferruzzi-Perri
    • , Natasha Pritchard
    • , Alesia Harper
    • , Natalie J. Hannan
    • , Valerie Kyritsis
    • , Nick Crinis
    • , Lisa Hui
    • , Susan P. Walker
    •  & Stephen Tong
  • Article
    | Open Access

    Developing noninvasive diagnostic biomarkers for lupus nephritis (LN) diagnosis is an important clinical goal. Here the authors identify urinary proteins correlated with active LN and disease severity, which differ across ethnicities but collectively outperform the current clinical method.

    • Samantha Stanley
    • , Kamala Vanarsa
    • , Samar Soliman
    • , Deena Habazi
    • , Claudia Pedroza
    • , Gabriel Gidley
    • , Ting Zhang
    • , Shree Mohan
    • , Evan Der
    • , Hemant Suryawanshi
    • , Thomas Tuschl
    • , Jill Buyon
    • , Chaim Putterman
    • , Chi Chiu Mok
    • , Michelle Petri
    • , Ramesh Saxena
    •  & Chandra Mohan
  • Article
    | Open Access

    The gut microbiota has been reported to regulate the efficacy of cancer therapy. Here, the authors show that short-chain fatty acids, which are generated through bacterial fermentation, increases immune tolerance leading to resistance to anti-CTLA-4 immunotherapy in mice and patients with metastatic melanoma.

    • Clélia Coutzac
    • , Jean-Mehdi Jouniaux
    • , Angelo Paci
    • , Julien Schmidt
    • , Domenico Mallardo
    • , Atmane Seck
    • , Vahe Asvatourian
    • , Lydie Cassard
    • , Patrick Saulnier
    • , Ludovic Lacroix
    • , Paul-Louis Woerther
    • , Aurore Vozy
    • , Marie Naigeon
    • , Laetitia Nebot-Bral
    • , Mélanie Desbois
    • , Ester Simeone
    • , Christine Mateus
    • , Lisa Boselli
    • , Jonathan Grivel
    • , Emilie Soularue
    • , Patricia Lepage
    • , Franck Carbonnel
    • , Paolo Antonio Ascierto
    • , Caroline Robert
    •  & Nathalie Chaput
  • Article
    | Open Access

    Molecular analysis of archival formalin-fixed clinical tissues can be difficult. Here, researchers have developed MethCORR, an approach that infers gene expression from DNA methylation data and use the approach for molecular characterization and prognostication of colorectal cancer using archival samples.

    • Trine B. Mattesen
    • , Mads H. Rasmussen
    • , Juan Sandoval
    • , Halit Ongen
    • , Sigrid S. Árnadóttir
    • , Josephine Gladov
    • , Anna Martinez-Cardus
    • , Manuel Castro de Moura
    • , Anders H. Madsen
    • , Søren Laurberg
    • , Emmanouil T. Dermitzakis
    • , Manel Esteller
    • , Claus L. Andersen
    •  & Jesper B. Bramsen
  • Article
    | Open Access

    Scavenger receptor-A (SR-A) is mostly expressed by myeloid cells and has been attributed a variety of biological functions. Here the authors assess SR-A as a biomarker for diagnosis of rheumatoid arthritis (RA) using large-scale training and validation cohorts and show that modulating SR-A levels can alter progression of collagen-induced arthritis in mice.

    • Fanlei Hu
    • , Xiang Jiang
    • , Chunqing Guo
    • , Yingni Li
    • , Shixian Chen
    • , Wei Zhang
    • , Yan Du
    • , Ping Wang
    • , Xi Zheng
    • , Xiangyu Fang
    • , Xin Li
    • , Jing Song
    • , Yang Xie
    • , Fei Huang
    • , Jimeng Xue
    • , Mingxin Bai
    • , Yuan Jia
    • , Xu Liu
    • , Limin Ren
    • , Xiaoying Zhang
    • , Jianping Guo
    • , Hudan Pan
    • , Yin Su
    • , Huanfa Yi
    • , Hua Ye
    • , Daming Zuo
    • , Juan Li
    • , Huaxiang Wu
    • , Yongfu Wang
    • , Ru Li
    • , Liang Liu
    • , Xiang-Yang Wang
    •  & Zhanguo Li
  • Article
    | Open Access

    In breast cancer, the claudin-low breast cancer subtype is remarkably diverse. Here, the authors propose that claudin-low is not a classical intrinsic breast cancer subtype, but rather a complex additional phenotype that can occur across intrinsic subtypes.

    • Christian Fougner
    • , Helga Bergholtz
    • , Jens Henrik Norum
    •  & Therese Sørlie
  • Article
    | Open Access

    Translocation renal cell carcinoma is an aggressive form of renal cancer that is often misdiagnosed to other subtypes. Here the authors demonstrated that by using machine learning and H&E stained whole-slide images, an accurate diagnose of this particular type of renal cancer can be achieved.

    • Jun Cheng
    • , Zhi Han
    • , Rohit Mehra
    • , Wei Shao
    • , Michael Cheng
    • , Qianjin Feng
    • , Dong Ni
    • , Kun Huang
    • , Liang Cheng
    •  & Jie Zhang
  • Article
    | Open Access

    The gold standard for diagnosis and monitoring of myocardial infarction is a chemiluminescence assay based on the detection of cardian troponin I (cTnI). Here, the authors develop a plasmonic gold nano-island chip assay for ultrasensitive detection of cTnI in as little as 10 μL of serum.

    • Wei Xu
    • , Lin Wang
    • , Ru Zhang
    • , Xuming Sun
    • , Lin Huang
    • , Haiyang Su
    • , Xunbin Wei
    • , Chia-Chun Chen
    • , Jiatao Lou
    • , Hongjie Dai
    •  & Kun Qian
  • Article
    | Open Access

    Cerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD) reflecting abnormal tau metabolism in the AD brain. Here the authors demonstrate that CSF p-tau217 shows better performance as an AD biomarker than p-tau181.

    • Shorena Janelidze
    • , Erik Stomrud
    • , Ruben Smith
    • , Sebastian Palmqvist
    • , Niklas Mattsson
    • , David C. Airey
    • , Nicholas K. Proctor
    • , Xiyun Chai
    • , Sergey Shcherbinin
    • , John R. Sims
    • , Gallen Triana-Baltzer
    • , Clara Theunis
    • , Randy Slemmon
    • , Marc Mercken
    • , Hartmuth Kolb
    • , Jeffrey L. Dage
    •  & Oskar Hansson
  • Article
    | Open Access

    It is not fully understood why some patients respond or do not respond to antidepressant treatment. Here the authors show that in the blood of individuals with depression, GPR56 expression increases in responders to antidepressant treatment, but not in non-responders.

    • Raoul Belzeaux
    • , Victor Gorgievski
    • , Laura M. Fiori
    • , Juan Pablo Lopez
    • , Julien Grenier
    • , Rixing Lin
    • , Corina Nagy
    • , El Chérif Ibrahim
    • , Eduardo Gascon
    • , Philippe Courtet
    • , Stéphane Richard-Devantoy
    • , Marcelo Berlim
    • , Eduardo Chachamovich
    • , Jean-François Théroux
    • , Sylvie Dumas
    • , Bruno Giros
    • , Susan Rotzinger
    • , Claudio N. Soares
    • , Jane A. Foster
    • , Naguib Mechawar
    • , Gregory G. Tall
    • , Eleni T. Tzavara
    • , Sidney H. Kennedy
    •  & Gustavo Turecki
  • Article
    | Open Access

    Mechanisms regulating the formation of pre-metastatic niches remain poorly understood. Here, the authors show that ITGBL1-containing extracellular vesicles derived from primary colorectal cancer cells activate the production of inflammatory cytokines by resident fibroblasts in distant organs, promoting metastatic cancer growth.

    • Qing Ji
    • , Lihong Zhou
    • , Hua Sui
    • , Liu Yang
    • , Xinnan Wu
    • , Qing Song
    • , Ru Jia
    • , Ruixiao Li
    • , Jian Sun
    • , Ziyuan Wang
    • , Ningning Liu
    • , Yuanyuan Feng
    • , Xiaoting Sun
    • , Gang Cai
    • , Yu Feng
    • , Jianfeng Cai
    • , Yihai Cao
    • , Guoxiang Cai
    • , Yan Wang
    •  & Qi Li
  • Article
    | Open Access

    Diagnosing acute infections based on transcriptional host response shows promise, but generalizability is wanting. Here, the authors use a co-normalization framework to train a classifier to diagnose acute infections and apply it to independent data on a targeted diagnostic platform.

    • Michael B. Mayhew
    • , Ljubomir Buturovic
    • , Roland Luethy
    • , Uros Midic
    • , Andrew R. Moore
    • , Jonasel A. Roque
    • , Brian D. Shaller
    • , Tola Asuni
    • , David Rawling
    • , Melissa Remmel
    • , Kirindi Choi
    • , James Wacker
    • , Purvesh Khatri
    • , Angela J. Rogers
    •  & Timothy E. Sweeney
  • Article
    | Open Access

    Sex and the APOE ε4 genotype are important risk factors for late-onset Alzheimer’s disease. In the current study, the authors investigate how sex and APOE ε4 genotype modify the association between Alzheimer’s disease biomarkers and metabolites in serum.

    • Matthias Arnold
    • , Kwangsik Nho
    • , Alexandra Kueider-Paisley
    • , Tyler Massaro
    • , Kevin Huynh
    • , Barbara Brauner
    • , Siamak MahmoudianDehkordi
    • , Gregory Louie
    • , M. Arthur Moseley
    • , J. Will Thompson
    • , Lisa St John-Williams
    • , Jessica D. Tenenbaum
    • , Colette Blach
    • , Rui Chang
    • , Roberta D. Brinton
    • , Rebecca Baillie
    • , Xianlin Han
    • , John Q. Trojanowski
    • , Leslie M. Shaw
    • , Ralph Martins
    • , Michael W. Weiner
    • , Eugenia Trushina
    • , Jon B. Toledo
    • , Peter J. Meikle
    • , David A. Bennett
    • , Jan Krumsiek
    • , P. Murali Doraiswamy
    • , Andrew J. Saykin
    • , Rima Kaddurah-Daouk
    •  & Gabi Kastenmüller
  • Article
    | Open Access

    Prostate cancer is often a multifocal disease but how best to manage this clinically remains unclear. Here, the authors report a single case study of a patient with two genetically diverse tumours which showed differential response to therapy.

    • Scott Wilkinson
    • , Stephanie A. Harmon
    • , Nicholas T. Terrigino
    • , Fatima Karzai
    • , Peter A. Pinto
    • , Ravi A. Madan
    • , David J. VanderWeele
    • , Ross Lake
    • , Rayann Atway
    • , John R. Bright
    • , Nicole V. Carrabba
    • , Shana Y. Trostel
    • , Rosina T. Lis
    • , Guinevere Chun
    • , James L. Gulley
    • , Maria J. Merino
    • , Peter L. Choyke
    • , Huihui Ye
    • , William L. Dahut
    • , Baris Turkbey
    •  & Adam G. Sowalsky
  • Article
    | Open Access

    Neurofilament (NfL) levels in CSF and blood have been established as a biomarker of neuronal damage in neurodegenerative diseases, and there is an age-dependent increase in NfL levels in CSF. Here the authors demonstrate that serum NfL levels increase in healthy aging people and predict and correlate with brain volume loss.

    • Michael Khalil
    • , Lukas Pirpamer
    • , Edith Hofer
    • , Margarete M. Voortman
    • , Christian Barro
    • , David Leppert
    • , Pascal Benkert
    • , Stefan Ropele
    • , Christian Enzinger
    • , Franz Fazekas
    • , Reinhold Schmidt
    •  & Jens Kuhle
  • Article
    | Open Access

    A locus on chromosome 1 encompassing the CFHR genes is highly associated with AMD risk. Here, Cipriani and colleagues investigate the role of CFHR4, encoding FHR-4, and demonstrate a relationship between AMD risk, circulating FHR-4 levels and genetic variants at this locus.

    • Valentina Cipriani
    • , Laura Lorés-Motta
    • , Fan He
    • , Dina Fathalla
    • , Viranga Tilakaratna
    • , Selina McHarg
    • , Nadhim Bayatti
    • , İlhan E. Acar
    • , Carel B. Hoyng
    • , Sascha Fauser
    • , Anthony T. Moore
    • , John R. W. Yates
    • , Eiko K. de Jong
    • , B. Paul Morgan
    • , Anneke I. den Hollander
    • , Paul N. Bishop
    •  & Simon J. Clark
  • Article
    | Open Access

    Diagnosis of vascular dementia is hampered by the lack of biochemical markers for this disease. Here, the authors show that vascular dementia is associated with increased lipocalin-2 in cerebrospinal fluid, compared to controls and patients with other forms of dementia.

    • Franc Llorens
    • , Peter Hermann
    • , Anna Villar-Piqué
    • , Daniela Diaz-Lucena
    • , Katarina Nägga
    • , Oskar Hansson
    • , Isabel Santana
    • , Matthias Schmitz
    • , Christian Schmidt
    • , Daniela Varges
    • , Stefan Goebel
    • , Julien Dumurgier
    • , Henrik Zetterberg
    • , Kaj Blennow
    • , Claire Paquet
    • , Inês Baldeiras
    • , Isidro Ferrer
    •  & Inga Zerr
  • Article
    | Open Access

    Identifying patients that will respond to a particular therapy remains a key challenge in precision oncology. Here, in gastric cancer, the authors show that circulating tumour DNA can predict recurrence, provided that the signal from white blood cells is filtered out.

    • Alessandro Leal
    • , Nicole C. T. van Grieken
    • , Doreen N. Palsgrove
    • , Jillian Phallen
    • , Jamie E. Medina
    • , Carolyn Hruban
    • , Mark A. M. Broeckaert
    • , Valsamo Anagnostou
    • , Vilmos Adleff
    • , Daniel C. Bruhm
    • , Jenna V. Canzoniero
    • , Jacob Fiksel
    • , Marianne Nordsmark
    • , Fabienne A. R. M. Warmerdam
    • , Henk M. W. Verheul
    • , Dick Johan van Spronsen
    • , Laurens V. Beerepoot
    • , Maud M. Geenen
    • , Johanneke E. A. Portielje
    • , Edwin P. M. Jansen
    • , Johanna van Sandick
    • , Elma Meershoek-Klein Kranenbarg
    • , Hanneke W. M. van Laarhoven
    • , Donald L. van der Peet
    • , Cornelis J. H. van de Velde
    • , Marcel Verheij
    • , Remond Fijneman
    • , Robert B. Scharpf
    • , Gerrit A. Meijer
    • , Annemieke Cats
    •  & Victor E. Velculescu
  • Article
    | Open Access

    Chronic lymphocytic leukemia is an indolent disease, and many patients succumb to infection rather than the direct effects of the disease. Here, the authors use medical records and machine learning to predict the patients that may be at risk of infection, which may enable a change in the course of their treatment.

    • Rudi Agius
    • , Christian Brieghel
    • , Michael A. Andersen
    • , Alexander T. Pearson
    • , Bruno Ledergerber
    • , Alessandro Cozzi-Lepri
    • , Yoram Louzoun
    • , Christen L. Andersen
    • , Jacob Bergstedt
    • , Jakob H. von Stemann
    • , Mette Jørgensen
    • , Man-Hung Eric Tang
    • , Magnus Fontes
    • , Jasmin Bahlo
    • , Carmen D. Herling
    • , Michael Hallek
    • , Jens Lundgren
    • , Cameron Ross MacPherson
    • , Jan Larsen
    •  & Carsten U. Niemann
  • Article
    | Open Access

    Mendelian randomization (MR) is a method for inferring causal relationships between risk factors and outcomes via associated genetic variants. Here, Burgess et al. develop the contamination mixture method which yields robust MR results in the presence of invalid instrumental variables and groups variants by their effect estimates.

    • Stephen Burgess
    • , Christopher N Foley
    • , Elias Allara
    • , James R Staley
    •  & Joanna M. M. Howson
  • Article
    | Open Access

    Here the authors provide a single-cell characterization of cerebrospinal fluid and blood of newly diagnosed multiple sclerosis (MS) patients, revealing altered composition of lymphocyte and monocyte subsets, validated by other methods including the interrogation of the TFH subset in mouse models of MS.

    • David Schafflick
    • , Chenling A. Xu
    • , Maike Hartlehnert
    • , Michael Cole
    • , Andreas Schulte-Mecklenbeck
    • , Tobias Lautwein
    • , Jolien Wolbert
    • , Michael Heming
    • , Sven G. Meuth
    • , Tanja Kuhlmann
    • , Catharina C. Gross
    • , Heinz Wiendl
    • , Nir Yosef
    •  & Gerd Meyer zu Horste
  • Article
    | Open Access

    An fMRI-based brain signature to predict an individual’s pain sensitivity could be useful clinically. Here the authors identify a network in the resting brain which can be used to predict responses to noxious stimuli in healthy subjects.

    • Tamas Spisak
    • , Balint Kincses
    • , Frederik Schlitt
    • , Matthias Zunhammer
    • , Tobias Schmidt-Wilcke
    • , Zsigmond T. Kincses
    •  & Ulrike Bingel
  • Article
    | Open Access

    Multivariable Mendelian randomization (MR) extends the standard MR framework to consider multiple risk factors in a single model. Here, Zuber et al. propose MR-BMA, a Bayesian variable selection approach to identify the likely causal determinants of a disease from many candidate risk factors as for example high-throughput data sets.

    • Verena Zuber
    • , Johanna Maria Colijn
    • , Caroline Klaver
    •  & Stephen Burgess
  • Article
    | Open Access

    Here, the authors characterize immunological and microbiome alterations in a cohort of obese asthmatics, finding that disease severity negatively correlates with fecal abundance of Akkermansia muciniphila, and show in a mouse model that administration of A. muciniphila reduces airway hyper-reactivity and airway inflammation.

    • David Michalovich
    • , Noelia Rodriguez-Perez
    • , Sylwia Smolinska
    • , Michal Pirozynski
    • , David Mayhew
    • , Sorif Uddin
    • , Stephanie Van Horn
    • , Milena Sokolowska
    • , Can Altunbulakli
    • , Andrzej Eljaszewicz
    • , Benoit Pugin
    • , Weronika Barcik
    • , Magdalena Kurnik-Lucka
    • , Ken A. Saunders
    • , Karen D. Simpson
    • , Peter Schmid-Grendelmeier
    • , Ruth Ferstl
    • , Remo Frei
    • , Noriane Sievi
    • , Malcolm Kohler
    • , Pawel Gajdanowicz
    • , Katrine B. Graversen
    • , Katrine Lindholm Bøgh
    • , Marek Jutel
    • , James R. Brown
    • , Cezmi A. Akdis
    • , Edith M. Hessel
    •  & Liam O’Mahony
  • Article
    | Open Access

    Siblings of those with autism spectrum disorder (ASD) have increased likelihood of ASD or related subclinical traits. Here, studying 253 ASD families, D’Abate et al. test the predictive value of genomic copy number variation involving ASD-associated loci, with confirmation in a second cohort.

    • L. D’Abate
    • , S. Walker
    • , R. K. C. Yuen
    • , K. Tammimies
    • , J. A. Buchanan
    • , R. W. Davies
    • , B. Thiruvahindrapuram
    • , J. Wei
    • , J. Brian
    • , S. E. Bryson
    • , K. Dobkins
    • , J. Howe
    • , R. Landa
    • , J. Leef
    • , D. Messinger
    • , S. Ozonoff
    • , I. M. Smith
    • , W. L. Stone
    • , Z. E. Warren
    • , G. Young
    • , L. Zwaigenbaum
    •  & S. W. Scherer
  • Article
    | Open Access

    Histology data exists for many cancer samples and the ability to automatically image this data may provide prognostic information. Here, the authors generated an algorithm to measure tumour infiltrating lymphocytes in melanoma histology specimens and show that the ratio of these immune cells to tumour cells has prognostic value.

    • Balazs Acs
    • , Fahad Shabbir Ahmed
    • , Swati Gupta
    • , Pok Fai Wong
    • , Robyn D. Gartrell
    • , Jaya Sarin Pradhan
    • , Emanuelle M. Rizk
    • , Bonnie Gould Rothberg
    • , Yvonne M. Saenger
    •  & David L. Rimm
  • Article
    | Open Access

    Predicting the drug response of patients with cancer is crucial for implementing targeted therapy. Here, Su et al. make patient-derived cell lines and perform targeted sequencing and RNA-seq to identify CDKN2A/2B loss as a predictor of response to CDK4/6 inhibitors in esophageal squamous cell carcinoma.

    • Dan Su
    • , Dadong Zhang
    • , Jiaoyue Jin
    • , Lisha Ying
    • , Miao Han
    • , Kaiyan Chen
    • , Bin Li
    • , Junzhou Wu
    • , Zhenghua Xie
    • , Fanrong Zhang
    • , Yihui Lin
    • , Guoping Cheng
    • , Jing-Yu Li
    • , Minran Huang
    • , Jinchao Wang
    • , Kailai Wang
    • , Jianjun Zhang
    • , Fugen Li
    • , Lei Xiong
    • , Andrew Futreal
    •  & Weimin Mao
  • Article
    | Open Access

    Risk of age-related chronic disorders and decrease in resilience is associated with ageing. Here the authors analyse the human blood metabolome and identify metabolites associated with frailty.

    • Nicholas J. W. Rattray
    • , Drupad K. Trivedi
    • , Yun Xu
    • , Tarani Chandola
    • , Caroline H. Johnson
    • , Alan D. Marshall
    • , Krisztina Mekli
    • , Zahra Rattray
    • , Gindo Tampubolon
    • , Bram Vanhoutte
    • , Iain R. White
    • , Frederick C. W. Wu
    • , Neil Pendleton
    • , James Nazroo
    •  & Royston Goodacre
  • Article
    | Open Access

    Knottin is a cystine knot peptide. Here, the authors develop a knottin-based tracer for positron emission tomography and demonstrate its ability to detect cancer and idiopathic pulmonary fibrosis through selective binding to integrin αvβ6.

    • Richard H. Kimura
    • , Ling Wang
    • , Bin Shen
    • , Li Huo
    • , Willemieke Tummers
    • , Fabian V. Filipp
    • , Haiwei Henry Guo
    • , Thomas Haywood
    • , Lotfi Abou-Elkacem
    • , Lucia Baratto
    • , Frezghi Habte
    • , Rammohan Devulapally
    • , Timothy H. Witney
    • , Yan Cheng
    • , Suhas Tikole
    • , Subhendu Chakraborti
    • , Jay Nix
    • , Christopher A. Bonagura
    • , Negin Hatami
    • , Joshua J. Mooney
    • , Tushar Desai
    • , Scott Turner
    • , Richard S. Gaster
    • , Andrea Otte
    • , Brendan C. Visser
    • , George A. Poultsides
    • , Jeffrey Norton
    • , Walter Park
    • , Mark Stolowitz
    • , Kenneth Lau
    • , Eric Yang
    • , Arutselvan Natarajan
    • , Ohad Ilovich
    • , Shyam Srinivas
    • , Ananth Srinivasan
    • , Ramasamy Paulmurugan
    • , Juergen Willmann
    • , Frederick T. Chin
    • , Zhen Cheng
    • , Andrei Iagaru
    • , Fang Li
    •  & Sanjiv S. Gambhir
  • Article
    | Open Access

    Immune-checkpoint inhibition therapy has achieved success in a subset of patients. Here the authors profiled about 200 relevant metabolites in patient serum samples from three independent immunotherapy trials and found the serum kynurenine/tryptophan ratio increases to be associated with worse overall survival.

    • Haoxin Li
    • , Kevin Bullock
    • , Carino Gurjao
    • , David Braun
    • , Sachet A. Shukla
    • , Dominick Bossé
    • , Aly-Khan A. Lalani
    • , Shuba Gopal
    • , Chelsea Jin
    • , Christine Horak
    • , Megan Wind-Rotolo
    • , Sabina Signoretti
    • , David F. McDermott
    • , Gordon J. Freeman
    • , Eliezer M. Van Allen
    • , Stuart L. Schreiber
    • , F. Stephen Hodi
    • , William R. Sellers
    • , Levi A. Garraway
    • , Clary B. Clish
    • , Toni K. Choueiri
    •  & Marios Giannakis
  • Article
    | Open Access

    Prostate cancer progression may be enhanced by a high-fat diet. Here the authors show that a diet high in saturated fats enhance the MYC-driven transcriptional program, a feature that independently predicts prostate cancer progression and death.

    • David P. Labbé
    • , Giorgia Zadra
    • , Meng Yang
    • , Jaime M. Reyes
    • , Charles Y. Lin
    • , Stefano Cacciatore
    • , Ericka M. Ebot
    • , Amanda L. Creech
    • , Francesca Giunchi
    • , Michelangelo Fiorentino
    • , Habiba Elfandy
    • , Sudeepa Syamala
    • , Edward D. Karoly
    • , Mohammed Alshalalfa
    • , Nicholas Erho
    • , Ashley Ross
    • , Edward M. Schaeffer
    • , Ewan A. Gibb
    • , Mandeep Takhar
    • , Robert B. Den
    • , Jonathan Lehrer
    • , R. Jeffrey Karnes
    • , Stephen J. Freedland
    • , Elai Davicioni
    • , Daniel E. Spratt
    • , Leigh Ellis
    • , Jacob D. Jaffe
    • , Anthony V. DʼAmico
    • , Philip W. Kantoff
    • , James E. Bradner
    • , Lorelei A. Mucci
    • , Jorge E. Chavarro
    • , Massimo Loda
    •  & Myles Brown
  • Article
    | Open Access

    The use of PET for detection of Aβ in the brain in AD has limitations; studies also indicate that retinal changes, including Aβ deposition, occur in AD. Here the authors demonstrate the potential to use in vivo retinal hyperspectral imaging as a surrogate for brain accumulation of Aβ.

    • Xavier Hadoux
    • , Flora Hui
    • , Jeremiah K. H. Lim
    • , Colin L. Masters
    • , Alice Pébay
    • , Sophie Chevalier
    • , Jason Ha
    • , Samantha Loi
    • , Christopher J. Fowler
    • , Christopher Rowe
    • , Victor L. Villemagne
    • , Edward N. Taylor
    • , Christopher Fluke
    • , Jean-Paul Soucy
    • , Frédéric Lesage
    • , Jean-Philippe Sylvestre
    • , Pedro Rosa-Neto
    • , Sulantha Mathotaarachchi
    • , Serge Gauthier
    • , Ziad S. Nasreddine
    • , Jean Daniel Arbour
    • , Marc-André Rhéaume
    • , Sylvain Beaulieu
    • , Mohamed Dirani
    • , Christine T. O. Nguyen
    • , Bang V. Bui
    • , Robert Williamson
    • , Jonathan G. Crowston
    •  & Peter van Wijngaarden
  • Article
    | Open Access

    Biomarkers that predict mortality are of interest for clinical as well as research applications. Here, the authors analyze metabolomics data from 44,168 individuals and identify key metabolites independently associated with all-cause mortality risk.

    • Joris Deelen
    • , Johannes Kettunen
    • , Krista Fischer
    • , Ashley van der Spek
    • , Stella Trompet
    • , Gabi Kastenmüller
    • , Andy Boyd
    • , Jonas Zierer
    • , Erik B. van den Akker
    • , Mika Ala-Korpela
    • , Najaf Amin
    • , Ayse Demirkan
    • , Mohsen Ghanbari
    • , Diana van Heemst
    • , M. Arfan Ikram
    • , Jan Bert van Klinken
    • , Simon P. Mooijaart
    • , Annette Peters
    • , Veikko Salomaa
    • , Naveed Sattar
    • , Tim D. Spector
    • , Henning Tiemeier
    • , Aswin Verhoeven
    • , Melanie Waldenberger
    • , Peter Würtz
    • , George Davey Smith
    • , Andres Metspalu
    • , Markus Perola
    • , Cristina Menni
    • , Johanna M. Geleijnse
    • , Fotios Drenos
    • , Marian Beekman
    • , J. Wouter Jukema
    • , Cornelia M. van Duijn
    •  & P. Eline Slagboom
  • Article
    | Open Access

    Microalbuminuria, a clinical marker associated with cancer and hypertension, defined by low albumin levels in the urine, is normally detected by immunoassay. Herein, a nanosensor paint was developed using a polymer to mimic fatty acid binding to albumin, transduced by carbon nanotube fluorescence.

    • Januka Budhathoki-Uprety
    • , Janki Shah
    • , Joshua A. Korsen
    • , Alysandria E. Wayne
    • , Thomas V. Galassi
    • , Joseph R. Cohen
    • , Jackson D. Harvey
    • , Prakrit V. Jena
    • , Lakshmi V. Ramanathan
    • , Edgar A. Jaimes
    •  & Daniel A. Heller
  • Article
    | Open Access

    In acute myeloid leukemia, hypomethylating agents decitabine and azacytidine are used interchangeably. Here, the authors show that the major metabolite of decitabine, but not azacytidine, is subject to SAMHD1 inactivation, highlighting SAMHD1 as a potential biomarker and therapeutic target

    • Thomas Oellerich
    • , Constanze Schneider
    • , Dominique Thomas
    • , Kirsten M. Knecht
    • , Olga Buzovetsky
    • , Lars Kaderali
    • , Christoph Schliemann
    • , Hanibal Bohnenberger
    • , Linus Angenendt
    • , Wolfgang Hartmann
    • , Eva Wardelmann
    • , Tamara Rothenburger
    • , Sebastian Mohr
    • , Sebastian Scheich
    • , Federico Comoglio
    • , Anne Wilke
    • , Philipp Ströbel
    • , Hubert Serve
    • , Martin Michaelis
    • , Nerea Ferreirós
    • , Gerd Geisslinger
    • , Yong Xiong
    • , Oliver T. Keppler
    •  & Jindrich Cinatl Jr.
  • Perspective
    | Open Access

    No effective therapies exist for dry age-related macular degeneration. In this perspective, the authors propose that research should emphasize system biology approaches that integrate various ‘omics’ data into mathematical models to establish pathogenic mechanisms on which to design novel treatments, and identify biomarkers that predict disease progression and therapeutic response.

    • James T. Handa
    • , Cathy Bowes Rickman
    • , Andrew D. Dick
    • , Michael B. Gorin
    • , Joan W. Miller
    • , Cynthia A. Toth
    • , Marius Ueffing
    • , Marco Zarbin
    •  & Lindsay A. Farrer
  • Article
    | Open Access

    Predominant participation of European-ancestry individuals in genetic studies has hindered the better understanding of genetic risk in non-European ancestry individuals. Here, Duncan et al. quantify polygenic risk score use and performance in worldwide populations.

    • L. Duncan
    • , H. Shen
    • , B. Gelaye
    • , J. Meijsen
    • , K. Ressler
    • , M. Feldman
    • , R. Peterson
    •  & B. Domingue
  • Article
    | Open Access

    There is no universal reference material to develop extracellular vesicle (EV) separation methods and carry out calibration and normalization. Here the authors use HIV-derived gag proteins to assemble recombinant fluorescent EV as a trackable reference material resembling the physical and biochemical properties of sample EV.

    • Edward Geeurickx
    • , Joeri Tulkens
    • , Bert Dhondt
    • , Jan Van Deun
    • , Lien Lippens
    • , Glenn Vergauwen
    • , Elisa Heyrman
    • , Delphine De Sutter
    • , Kris Gevaert
    • , Francis Impens
    • , Ilkka Miinalainen
    • , Pieter-Jan Van Bockstal
    • , Thomas De Beer
    • , Marca H. M. Wauben
    • , Esther N. M. Nolte-‘t-Hoen
    • , Katarzyna Bloch
    • , Johannes V. Swinnen
    • , Edwin van der Pol
    • , Rienk Nieuwland
    • , Geert Braems
    • , Nico Callewaert
    • , Pieter Mestdagh
    • , Jo Vandesompele
    • , Hannelore Denys
    • , Sven Eyckerman
    • , Olivier De Wever
    •  & An Hendrix
  • Article
    | Open Access

    Epigenetic differences in nasal epithelium have been proposed as a biomarker for lower airway disease and asthma. Here, in epigenome-wide association studies for asthma and other airway traits using nasal swabs, the authors identify differentially methylated CpGs that highlight genes involved in TH2 response.

    • Andres Cardenas
    • , Joanne E. Sordillo
    • , Sheryl L. Rifas-Shiman
    • , Wonil Chung
    • , Liming Liang
    • , Brent A. Coull
    • , Marie-France Hivert
    • , Peggy S. Lai
    • , Erick Forno
    • , Juan C. Celedón
    • , Augusto A. Litonjua
    • , Kasey J. Brennan
    • , Dawn L. DeMeo
    • , Andrea A. Baccarelli
    • , Emily Oken
    •  & Diane R. Gold
  • Article
    | Open Access

    Dimethyl fumarate (DMF) is an established treatment for relapsing multiple sclerosis with unclear mechanism of action. Here the authors distinguish DMF responders by monocyte counts and redox gene signature in a prospective longitudinal cohort at 3 month of therapy, and associate NOX3 genetic variants with outcome.

    • Karl E. Carlström
    • , Ewoud Ewing
    • , Mathias Granqvist
    • , Alexandra Gyllenberg
    • , Shahin Aeinehband
    • , Sara Lind Enoksson
    • , Antonio Checa
    • , Tejaswi V. S. Badam
    • , Jesse Huang
    • , David Gomez-Cabrero
    • , Mika Gustafsson
    • , Faiez Al Nimer
    • , Craig E. Wheelock
    • , Ingrid Kockum
    • , Tomas Olsson
    • , Maja Jagodic
    •  & Fredrik Piehl
  • Article
    | Open Access

    Zero-field nuclear magnetic resonance can identify species and collective behaviors in mixtures without applied magnetic fields. Here the authors demonstrate its use for resolving proton exchange in ammonium and for the detection of hyperpolarized pyruvic acid, an important imaging biomarker.

    • Danila A. Barskiy
    • , Michael C. D. Tayler
    • , Irene Marco-Rius
    • , John Kurhanewicz
    • , Daniel B. Vigneron
    • , Sevil Cikrikci
    • , Ayca Aydogdu
    • , Moritz Reh
    • , Andrey N. Pravdivtsev
    • , Jan-Bernd Hövener
    • , John W. Blanchard
    • , Teng Wu
    • , Dmitry Budker
    •  & Alexander Pines
  • Article
    | Open Access

    The use of of CDK4/6 inhibitors to treat patients with TNBC is limited by loss of Rb. Here, the authors show that a combination of CDK4/6 inhibitor and EGFR inhibitor is effective against DEDD-overexpressing TNBC, independent of Rb status.

    • Yingjia Ni
    • , Keon R. Schmidt
    • , Barnes A. Werner
    • , Jenna K. Koenig
    • , Ian H. Guldner
    • , Patricia M. Schnepp
    • , Xuejuan Tan
    • , Lan Jiang
    • , Misha Host
    • , Longhua Sun
    • , Erin N. Howe
    • , Junmin Wu
    • , Laurie E. Littlepage
    • , Harikrishna Nakshatri
    •  & Siyuan Zhang
  • Article
    | Open Access

    Patterns of brain activity during sleep in early stages of life influence brain development and behavior. Here, the authors reveal cortical dynamics underpinning quiet and active sleep states in pre- and full-term infants, and their links to neurodevelopmental outcomes.

    • Anton Tokariev
    • , James A. Roberts
    • , Andrew Zalesky
    • , Xuelong Zhao
    • , Sampsa Vanhatalo
    • , Michael Breakspear
    •  & Luca Cocchi
  • Article
    | Open Access

    Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

    • Darina Czamara
    • , Gökçen Eraslan
    • , Christian M. Page
    • , Jari Lahti
    • , Marius Lahti-Pulkkinen
    • , Esa Hämäläinen
    • , Eero Kajantie
    • , Hannele Laivuori
    • , Pia M. Villa
    • , Rebecca M. Reynolds
    • , Wenche Nystad
    • , Siri E. Håberg
    • , Stephanie J. London
    • , Kieran J. O’Donnell
    • , Elika Garg
    • , Michael J. Meaney
    • , Sonja Entringer
    • , Pathik D. Wadhwa
    • , Claudia Buss
    • , Meaghan J. Jones
    • , David T. S. Lin
    • , Julie L. MacIsaac
    • , Michael S. Kobor
    • , Nastassja Koen
    • , Heather J. Zar
    • , Karestan C. Koenen
    • , Shareefa Dalvie
    • , Dan J. Stein
    • , Ivan Kondofersky
    • , Nikola S. Müller
    • , Fabian J. Theis
    • , Naomi R. Wray
    • , Stephan Ripke
    • , Manuel Mattheisen
    • , Maciej Trzaskowski
    • , Enda M. Byrne
    • , Abdel Abdellaoui
    • , Mark J. Adams
    • , Esben Agerbo
    • , Tracy M. Air
    • , Till F. M. Andlauer
    • , Silviu-Alin Bacanu
    • , Marie Bækvad-Hansen
    • , Aartjan T. F. Beekman
    • , Tim B. Bigdeli
    • , Douglas H. R. Blackwood
    • , Julien Bryois
    • , Henriette N. Buttenschøn
    • , Jonas Bybjerg-Grauholm
    • , Na Cai
    • , Enrique Castelao
    • , Jane Hvarregaard Christensen
    • , Toni-Kim Clarke
    • , Jonathan R. I. Coleman
    • , Lucía Colodro-Conde
    • , Baptiste Couvy-Duchesne
    • , Nick Craddock
    • , Gregory E. Crawford
    • , Gail Davies
    • , Ian J. Deary
    • , Franziska Degenhardt
    • , Eske M. Derks
    • , Nese Direk
    • , Conor V. Dolan
    • , Erin C. Dunn
    • , Thalia C. Eley
    • , Valentina Escott-Price
    • , Farnush Farhadi Hassan Kiadeh
    • , Hilary K. Finucane
    • , Andreas J. Forstner
    • , Josef Frank
    • , Héléna A. Gaspar
    • , Michael Gill
    • , Fernando S. Goes
    • , Scott D. Gordon
    • , Jakob Grove
    • , Lynsey S. Hall
    • , Christine Søholm Hansen
    • , Thomas F. Hansen
    • , Stefan Herms
    • , Ian B. Hickie
    • , Per Hoffmann
    • , Georg Homuth
    • , Carsten Horn
    • , Jouke-Jan Hottenga
    • , David M. Hougaard
    • , Marcus Ising
    • , Rick Jansen
    • , Eric Jorgenson
    • , James A. Knowles
    • , Isaac S. Kohane
    • , Julia Kraft
    • , Warren W. Kretzschmar
    • , Jesper Krogh
    • , Zoltán Kutalik
    • , Yihan Li
    • , Penelope A. Lind
    • , Donald J. MacIntyre
    • , Dean F. MacKinnon
    • , Robert M. Maier
    • , Wolfgang Maier
    • , Jonathan Marchini
    • , Hamdi Mbarek
    • , Patrick McGrath
    • , Peter McGuffin
    • , Sarah E. Medland
    • , Divya Mehta
    • , Christel M. Middeldorp
    • , Evelin Mihailov
    • , Yuri Milaneschi
    • , Lili Milani
    • , Francis M. Mondimore
    • , Grant W. Montgomery
    • , Sara Mostafavi
    • , Niamh Mullins
    • , Matthias Nauck
    • , Bernard Ng
    • , Michel G. Nivard
    • , Dale R. Nyholt
    • , Paul F. O’Reilly
    • , Hogni Oskarsson
    • , Michael J. Owen
    • , Jodie N. Painter
    • , Carsten Bøcker Pedersen
    • , Marianne Giørtz Pedersen
    • , Roseann E. Peterson
    • , Erik Pettersson
    • , Wouter J. Peyrot
    • , Giorgio Pistis
    • , Danielle Posthuma
    • , Jorge A. Quiroz
    • , Per Qvist
    • , John P. Rice
    • , Brien P. Riley
    • , Margarita Rivera
    • , Saira Saeed Mirza
    • , Robert Schoevers
    • , Eva C. Schulte
    • , Ling Shen
    • , Jianxin Shi
    • , Stanley I. Shyn
    • , Engilbert Sigurdsson
    • , Grant C. B. Sinnamon
    • , Johannes H. Smit
    • , Daniel J. Smith
    • , Hreinn Stefansson
    • , Stacy Steinberg
    • , Fabian Streit
    • , Jana Strohmaier
    • , Katherine E. Tansey
    • , Henning Teismann
    • , Alexander Teumer
    • , Wesley Thompson
    • , Pippa A. Thomson
    • , Thorgeir E. Thorgeirsson
    • , Matthew Traylor
    • , Jens Treutlein
    • , Vassily Trubetskoy
    • , André G. Uitterlinden
    • , Daniel Umbricht
    • , Sandra Van der Auwera
    • , Albert M. van Hemert
    • , Alexander Viktorin
    • , Peter M. Visscher
    • , Yunpeng Wang
    • , Bradley T. Webb
    • , Shantel Marie Weinsheimer
    • , Jürgen Wellmann
    • , Gonneke Willemsen
    • , Stephanie H. Witt
    • , Yang Wu
    • , Hualin S. Xi
    • , Jian Yang
    • , Futao Zhang
    • , Volker Arolt
    • , Bernhard T. Baune
    • , Klaus Berger
    • , Dorret I. Boomsma
    • , Sven Cichon
    • , Udo Dannlowski
    • , E. J. C. de Geus
    • , J. Raymond DePaulo
    • , Enrico Domenici
    • , Katharina Domschke
    • , Tõnu Esko
    • , Hans J. Grabe
    • , Steven P. Hamilton
    • , Caroline Hayward
    • , Andrew C. Heath
    • , Kenneth S. Kendler
    • , Stefan Kloiber
    • , Glyn Lewis
    • , Qingqin S. Li
    • , Susanne Lucae
    • , Pamela A. F. Madden
    • , Patrik K. Magnusson
    • , Nicholas G. Martin
    • , Andrew M. McIntosh
    • , Andres Metspalu
    • , Ole Mors
    • , Preben Bo Mortensen
    • , Bertram Müller-Myhsok
    • , Merete Nordentoft
    • , Markus M. Nöthen
    • , Michael C. O’Donovan
    • , Sara A. Paciga
    • , Nancy L. Pedersen
    • , Brenda W. J. H. Penninx
    • , Roy H. Perlis
    • , David J. Porteous
    • , James B. Potash
    • , Martin Preisig
    • , Marcella Rietschel
    • , Catherine Schaefer
    • , Thomas G. Schulze
    • , Jordan W. Smoller
    • , Kari Stefansson
    • , Henning Tiemeier
    • , Rudolf Uher
    • , Henry Völzke
    • , Myrna M. Weissman
    • , Thomas Werge
    • , Cathryn M. Lewis
    • , Douglas F. Levinson
    • , Gerome Breen
    • , Anders D. Børglum
    • , Patrick F. Sullivan
    • , Katri Räikkönen
    •  & Elisabeth B. Binder
  • Article
    | Open Access

    Protein degradation in clinical samples is largely unexplored. Here, the authors analyze the transcriptome and proteome of clinical tissue samples and develop an algorithm to assess protein degradation, showing that protein degradation is negligible in most tissue samples and does not correlate with transcript degradation.

    • Wenguang Shao
    • , Tiannan Guo
    • , Nora C. Toussaint
    • , Peng Xue
    • , Ulrich Wagner
    • , Li Li
    • , Konstantina Charmpi
    • , Yi Zhu
    • , Jianmin Wu
    • , Marija Buljan
    • , Rui Sun
    • , Dorothea Rutishauser
    • , Thomas Hermanns
    • , Christian Daniel Fankhauser
    • , Cedric Poyet
    • , Jelena Ljubicic
    • , Niels Rupp
    • , Jan H. Rüschoff
    • , Qing Zhong
    • , Andreas Beyer
    • , Jiafu Ji
    • , Ben C. Collins
    • , Yansheng Liu
    • , Gunnar Rätsch
    • , Peter J. Wild
    •  & Ruedi Aebersold
  • Article
    | Open Access

    LKB1 is frequently mutated in lung squamous cell carcinomas. Here, the authors show that sole LKB1 depletion is sufficient to drive the development of this cancer, where downstream defective MKK7-JNK1/2 signalling activates the ∆Np63/p63 pathway to induce subsequent epithelial cells transformation and tumour progression.

    • Jian Liu
    • , Tianyuan Wang
    • , Chad J. Creighton
    • , San-Pin Wu
    • , Madhumita Ray
    • , Kyathanahalli S. Janardhan
    • , Cynthia J. Willson
    • , Sung-Nam Cho
    • , Patricia D. Castro
    • , Michael M. Ittmann
    • , Jian-Liang Li
    • , Roger J. Davis
    •  & Francesco J. DeMayo
  • Article
    | Open Access

    Structural variations in gastric cancer impact progression. Here, the authors perform whole-genome sequencing on 168 gastric cancer patients and identified tandem-duplications of super-enhancer ZFP36L2 in 10% of gastric cancer, and mutational signatures in tumors with cadherin 1 mutations that associated with poor prognoses.

    • Rui Xing
    • , Yong Zhou
    • , Jun Yu
    • , Yingyan Yu
    • , Yongzhan Nie
    • , Wen Luo
    • , Chao Yang
    • , Teng Xiong
    • , William K. K. Wu
    • , Zhongwu Li
    • , Yang Bing
    • , Shuye Lin
    • , Yaping Zhang
    • , Yingqi Hu
    • , Lin Li
    • , Lijuan Han
    • , Chen Yang
    • , Shaogang Huang
    • , Suiping Huang
    • , Rui Zhou
    • , Jing Li
    • , Kaichun Wu
    • , Daiming Fan
    • , Guangbo Tang
    • , Jianhua Dou
    • , Zhenggang Zhu
    • , Jiafu Ji
    • , Xiaodong Fang
    •  & Youyong Lu