Biomarkers

  • Article | | open

    Here, the authors explore the relationship between socioeconomic position (SEP) across the life course and inflammation in a multi-cohort study and show that educational attainment is most strongly related to inflammation, suggesting that socioeconomic disadvantage in young adulthood is independently associated with later life inflammation.

    • Eloïse Berger
    • , Raphaële Castagné
    • , Marc Chadeau-Hyam
    • , Murielle Bochud
    • , Angelo d’Errico
    • , Martina Gandini
    • , Maryam Karimi
    • , Mika Kivimäki
    • , Vittorio Krogh
    • , Michael Marmot
    • , Salvatore Panico
    • , Martin Preisig
    • , Fulvio Ricceri
    • , Carlotta Sacerdote
    • , Andrew Steptoe
    • , Silvia Stringhini
    • , Rosario Tumino
    • , Paolo Vineis
    • , Cyrille Delpierre
    •  & Michelle Kelly-Irving
  • Article | | open

    Diverse interactions between the nervous and immune systems have been shown, but specific mechanistic insights are still lacking. Here the authors show, using both mouse inflammation models and clinical correlation, that adrenergic nerve may ameliorate inflammation by inducing repulsive guidance molecule A signalling.

    • Andreas Körner
    • , Martin Schlegel
    • , Torsten Kaussen
    • , Verena Gudernatsch
    • , Georg Hansmann
    • , Timo Schumacher
    • , Martin Giera
    •  & Valbona Mirakaj
  • Article | | open

    FLT3 is commonly mutated in acute myeloid leukaemia and treatment with FLT3 inhibitors often ends with relapse. Here, the authors perform exome sequencing of samples from patients treated with the FLT3 inhibitor, crenolanib, to show that resistance occurs due to diverse molecular mechanisms, not primarily due to secondary FLT3 mutations.

    • Haijiao Zhang
    • , Samantha Savage
    • , Anna Reister Schultz
    • , Daniel Bottomly
    • , Libbey White
    • , Erik Segerdell
    • , Beth Wilmot
    • , Shannon K. McWeeney
    • , Christopher A. Eide
    • , Tamilla Nechiporuk
    • , Amy Carlos
    • , Rachel Henson
    • , Chenwei Lin
    • , Robert Searles
    • , Hoang Ho
    • , Yee Ling Lam
    • , Richard Sweat
    • , Courtney Follit
    • , Vinay Jain
    • , Evan Lind
    • , Gautam Borthakur
    • , Guillermo Garcia-Manero
    • , Farhad Ravandi
    • , Hagop M. Kantarjian
    • , Jorge Cortes
    • , Robert Collins
    • , Daelynn R. Buelow
    • , Sharyn D. Baker
    • , Brian J. Druker
    •  & Jeffrey W. Tyner
  • Article | | open

    In gene regulation, diversification at the transcriptome 3′end is linked to differentiation and dedifferentiation. Here, the authors discover extensive transcriptome 3′end-alterations in neuroblastoma, regulated by PCF11, and provide an interactive data repository of transcriptome-wide alternative polyadenylation.

    • Anton Ogorodnikov
    • , Michal Levin
    • , Surendra Tattikota
    • , Sergey Tokalov
    • , Mainul Hoque
    • , Denise Scherzinger
    • , Federico Marini
    • , Ansgar Poetsch
    • , Harald Binder
    • , Stephan Macher-Göppinger
    • , Hans Christian Probst
    • , Bin Tian
    • , Michael Schaefer
    • , Karl J. Lackner
    • , Frank Westermann
    •  & Sven Danckwardt
  • Article | | open

    The tuberculosis pandemic requires new methods for diagnosing and containing infections prior to active disease. Here, the authors performed a multi-site observational study within sub-Saharan Africa and present serum and plasma metabolic signatures that can predict the onset of active TB with a high degree of sensitivity and specificity.

    • January Weiner 3rd
    • , Jeroen Maertzdorf
    • , Jayne S. Sutherland
    • , Fergal J. Duffy
    • , Ethan Thompson
    • , Sara Suliman
    • , Gayle McEwen
    • , Bonnie Thiel
    • , Shreemanta K. Parida
    • , Joanna Zyla
    • , Willem A. Hanekom
    • , Robert P. Mohney
    • , W. Henry Boom
    • , Harriet Mayanja-Kizza
    • , Rawleigh Howe
    • , Hazel M. Dockrell
    • , Tom H. M. Ottenhoff
    • , Thomas J. Scriba
    • , Daniel E. Zak
    • , Gerhard Walzl
    • , Stefan H. E. Kaufmann
    • , Almaz Abebe
    • , Brian Abel
    • , Richard Adegbola
    • , Ifedayo Adetifa
    • , Lyn Ambrose
    • , Peter Andersen
    • , Martin Antonio
    • , Abraham Aseffa
    • , Debbie van Baarle
    • , Lew Barker
    • , Yonas Bekele
    • , Nicole Bilek
    • , Gillian F. Black
    • , Mark Bowmaker
    • , Keith Branson
    • , Michael Brennan
    • , Novel N. Chegou
    • , Femia Chilongo
    • , William Kwong Chung
    • , Tumani Corrah
    • , Ameilia C. Crampin
    • , Mark Doherty
    • , Gregory Dolganov
    • , Simon Donkor
    • , Katrina Downing
    • , Michelle Fisher
    • , Kees L. M. C. Franken
    • , Neil French
    • , Larry Geiter
    • , Annemieke Geluk
    • , Robert Golinski
    • , Patricia Gorak-Stolinska
    • , Marielle C. Haks
    • , Philip Hill
    • , Jane Hughes
    • , Yun-Gyoung Hur
    • , Rachel Iwnetu
    • , Marc Jacobson
    • , Moses Joloba
    • , Simone A. Joosten
    • , Benjamin Kagina
    • , Desta Kassa
    • , Hussein Kisingo
    • , Michel R. Klein
    • , Magdalena Kriel
    • , Maeve Lalor
    • , Ji-Sook Lee
    • , Andre G. Loxton
    • , Hassan Mahomed
    • , Krista E. van Meijgaarden
    • , Tsehayenesh Mesele
    • , Frank Miedema
    • , Adane Mihret
    • , Humphrey Mulenga
    • , Stefanie Muller
    • , Hazzie Mvula
    • , Nonhlanhla Nene
    • , Bagrey Ngwira
    • , Mary Nsereko
    • , Brenda Okwera
    • , Martin Ota
    • , Adam Penn-Nicholson
    • , Nelita Du Plessis
    • , S. Ramachandran
    • , Ida Rosenkrands
    • , Jerry Sadoff
    • , Jacky Saul
    • , Gary Schoolnik
    • , Felanji Simukonda
    • , Donata Sizemore
    • , Steven Smith
    • , Anne Ben Smith
    • , Gian van der Spuy
    • , Kim Stanley
    • , David Tabb
    • , Mesfin Tafesse
    • , Belete Tegbaru
    • , Toyin Togun
    • , Gerhardus Tromp
    • , Tran Van
    • , Kate Watkins
    • , Frank Weichold
    • , Karin Weldingh
    • , Lawrence Yamuah
    •  & Sarah Zalwango
  • Article | | open

    DNA methylation is an epigenetic modification that control genetic programs. Here, the authors found that the methylation landscape influences the physicochemical properties of DNA and that it can serve as a universal cancer biomarker, and developed a one-step assay for the detection of cancer DNA.

    • Abu Ali Ibn Sina
    • , Laura G. Carrascosa
    • , Ziyu Liang
    • , Yadveer S. Grewal
    • , Andri Wardiana
    • , Muhammad J. A. Shiddiky
    • , Robert A. Gardiner
    • , Hemamali Samaratunga
    • , Maher K. Gandhi
    • , Rodney J. Scott
    • , Darren Korbie
    •  & Matt Trau
  • Article | | open

    The methylation status of circulating cell-free DNA (cfDNA) can be informative about recent cell death events. Here the authors present an approach to determine the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types, and find that cfDNA from patients reveals tissue contributions that agree with clinical findings.

    • Joshua Moss
    • , Judith Magenheim
    • , Daniel Neiman
    • , Hai Zemmour
    • , Netanel Loyfer
    • , Amit Korach
    • , Yaacov Samet
    • , Myriam Maoz
    • , Henrik Druid
    • , Peter Arner
    • , Keng-Yeh Fu
    • , Endre Kiss
    • , Kirsty L. Spalding
    • , Giora Landesberg
    • , Aviad Zick
    • , Albert Grinshpun
    • , A. M. James Shapiro
    • , Markus Grompe
    • , Avigail Dreazan Wittenberg
    • , Benjamin Glaser
    • , Ruth Shemer
    • , Tommy Kaplan
    •  & Yuval Dor
  • Article | | open

    Accurate and actionable biomarkers that integrate diverse molecular, functional and clinical information hold great promise in precision medicine. Here, the authors develop SIMMS, a method for pathway-based cross-disease biomarker discovery.

    • Syed Haider
    • , Cindy Q. Yao
    • , Vicky S. Sabine
    • , Michal Grzadkowski
    • , Vincent Stimper
    • , Maud H. W. Starmans
    • , Jianxin Wang
    • , Francis Nguyen
    • , Nathalie C. Moon
    • , Xihui Lin
    • , Camilla Drake
    • , Cheryl A. Crozier
    • , Cassandra L. Brookes
    • , Cornelis J. H. van de Velde
    • , Annette Hasenburg
    • , Dirk G. Kieback
    • , Christos J. Markopoulos
    • , Luc Y. Dirix
    • , Caroline Seynaeve
    • , Daniel W. Rea
    • , Arek Kasprzyk
    • , Philippe Lambin
    • , Pietro Lio’
    • , John M. S. Bartlett
    •  & Paul C. Boutros
  • Article | | open

    Diagnostic tests need optimization to avoid invasive and costly repeated biopsies. Here the authors present an antibody-DNA barcoding approach where harvested single cells can be re-stained through custom oligonucleotide-fluorophore conjugates, enabling multiplexed analysis of cancer pathways.

    • Randy J. Giedt
    • , Divya Pathania
    • , Jonathan C. T. Carlson
    • , Philip J. McFarland
    • , Andres Fernandez del Castillo
    • , Dejan Juric
    •  & Ralph Weissleder
  • Article | | open

    FISH-based techniques to image and count mRNA in single cells can be limited by the photophysical properties of organic dyes. Here the authors develop photostable quantum dot FISH probes for multiplexed imaging.

    • Yang Liu
    • , Phuong Le
    • , Sung Jun Lim
    • , Liang Ma
    • , Suresh Sarkar
    • , Zhiyuan Han
    • , Stephen J. Murphy
    • , Farhad Kosari
    • , George Vasmatzis
    • , John C. Cheville
    •  & Andrew M. Smith
  • Article | | open

    The response to respiratory virus exposure can currently not be predicted by pre- or early post-exposure molecular signatures. Here, the authors conduct a community-based analysis of blood gene expression from healthy individuals exposed to respiratory viruses and provide predictive models and biological insight into the physiological response.

    • Slim Fourati
    • , Aarthi Talla
    • , Mehrad Mahmoudian
    • , Joshua G. Burkhart
    • , Riku Klén
    • , Ricardo Henao
    • , Thomas Yu
    • , Zafer Aydın
    • , Ka Yee Yeung
    • , Mehmet Eren Ahsen
    • , Reem Almugbel
    • , Samad Jahandideh
    • , Xiao Liang
    • , Torbjörn E. M. Nordling
    • , Motoki Shiga
    • , Ana Stanescu
    • , Robert Vogel
    • , Emna Ben Abdallah
    • , Farnoosh Abbas Aghababazadeh
    • , Alicia Amadoz
    • , Sherry Bhalla
    • , Kevin Bleakley
    • , Erika Bongen
    • , Domenico Borzacchielo
    • , Philipp Bucher
    • , Jose Carbonell-Caballero
    • , Kumardeep Chaudhary
    • , Francisco Chinesta
    • , Prasad Chodavarapu
    • , Ryan D Chow
    • , Thomas Cokelaer
    • , Cankut Cubuk
    • , Sandeep Kumar Dhanda
    • , Joaquin Dopazo
    • , Thomas Faux
    • , Yang Feng
    • , Christofer Flinta
    • , Carito Guziolowski
    • , Di He
    • , Marta R. Hidalgo
    • , Jiayi Hou
    • , Katsumi Inoue
    • , Maria K Jaakkola
    • , Jiadong Ji
    • , Ritesh Kumar
    • , Sunil Kumar
    • , Miron Bartosz Kursa
    • , Qian Li
    • , Michał Łopuszyński
    • , Pengcheng Lu
    • , Morgan Magnin
    • , Weiguang Mao
    • , Bertrand Miannay
    • , Iryna Nikolayeva
    • , Zoran Obradovic
    • , Chi Pak
    • , Mohammad M. Rahman
    • , Misbah Razzaq
    • , Tony Ribeiro
    • , Olivier Roux
    • , Ehsan Saghapour
    • , Harsh Saini
    • , Shamim Sarhadi
    • , Hiroki Sato
    • , Benno Schwikowski
    • , Alok Sharma
    • , Ronesh Sharma
    • , Deepak Singla
    • , Ivan Stojkovic
    • , Tomi Suomi
    • , Maria Suprun
    • , Chengzhe Tian
    • , Lewis E. Tomalin
    • , Lei Xie
    • , Xiang Yu
    • , Gaurav Pandey
    • , Christopher Chiu
    • , Micah T. McClain
    • , Christopher W. Woods
    • , Geoffrey S. Ginsburg
    • , Laura L. Elo
    • , Ephraim L. Tsalik
    • , Lara M. Mangravite
    •  & Solveig K. Sieberts
  • Article | | open

    Patients with myotonic dystrophy need to undergo invasive muscle biopsies to monitor disease progression and response to therapy. Here, the authors show that extracellular RNAs in human urine can be used as biomarkers to differentiate patients from unaffected controls, and to monitor exon skipping in patients with Duchenne muscular dystrophy taking the drug eteplirsen.

    • Layal Antoury
    • , Ningyan Hu
    • , Leonora Balaj
    • , Sudeshna Das
    • , Sofia Georghiou
    • , Basil Darras
    • , Tim Clark
    • , Xandra O. Breakefield
    •  & Thurman M. Wheeler
  • Article | | open

    Brain function alterations in schizophrenia and other psychotic disorders remain poorly understood. Here, the authors discover that increased neural connectivity in the cerebello-thalamo-cortical circuitry predicts psychosis in those at high risk, and is present in people with schizophrenia.

    • Hengyi Cao
    • , Oliver Y. Chén
    • , Yoonho Chung
    • , Jennifer K. Forsyth
    • , Sarah C. McEwen
    • , Dylan G. Gee
    • , Carrie E. Bearden
    • , Jean Addington
    • , Bradley Goodyear
    • , Kristin S. Cadenhead
    • , Heline Mirzakhanian
    • , Barbara A. Cornblatt
    • , Ricardo E. Carrión
    • , Daniel H. Mathalon
    • , Thomas H. McGlashan
    • , Diana O. Perkins
    • , Aysenil Belger
    • , Larry J. Seidman
    • , Heidi Thermenos
    • , Ming T. Tsuang
    • , Theo G. M. van Erp
    • , Elaine F. Walker
    • , Stephan Hamann
    • , Alan Anticevic
    • , Scott W. Woods
    •  & Tyrone D. Cannon
  • Article | | open

    People vary in the extent to which they feel better after taking an inert, placebo, treatment, but the basis for individual placebo response is unclear. Here, the authors show how brain structural and functional variables, as well as personality traits, predict placebo response in those with chronic back pain.

    • Etienne Vachon-Presseau
    • , Sara E. Berger
    • , Taha B. Abdullah
    • , Lejian Huang
    • , Guillermo A. Cecchi
    • , James W. Griffith
    • , Thomas J. Schnitzer
    •  & A. Vania Apkarian
  • Article | | open

    Upstream pathways regulating Brg1 stability and their role in carcinogenesis are unknown. Here they show Brg1 to be phosphorylated by CK1δ to promote its ubiquitination by SCFFBW7 (FBW7), Brg1 stabilization to promote gastric cancer metastasis, and suggest targeting Brg1 in FBW7 compromised gastric cancer.

    • Li-Yu Huang
    • , Junjie Zhao
    • , Hao Chen
    • , Lixin Wan
    • , Hiroyuki Inuzuka
    • , Jianping Guo
    • , Xuhong Fu
    • , Yangyang Zhai
    • , Zhaoning Lu
    • , Xuefei Wang
    • , Ze-Guang Han
    • , Yihong Sun
    •  & Wenyi Wei
  • Article | | open

    Biomarker identification requires prohibitively large cohorts with gene expression and phenotype data. The approach introduced here learns polygenic predictors of expression from genetic and expression data, used to infer biomarker levels in patients with genetic and disease information.

    • Jonathan D. Mosley
    • , QiPing Feng
    • , Quinn S. Wells
    • , Sara L. Van Driest
    • , Christian M. Shaffer
    • , Todd L. Edwards
    • , Lisa Bastarache
    • , Wei-Qi Wei
    • , Lea K. Davis
    • , Catherine A. McCarty
    • , Will Thompson
    • , Christopher G. Chute
    • , Gail P. Jarvik
    • , Adam S. Gordon
    • , Melody R. Palmer
    • , David R. Crosslin
    • , Eric B. Larson
    • , David S. Carrell
    • , Iftikhar J. Kullo
    • , Jennifer A. Pacheco
    • , Peggy L. Peissig
    • , Murray H. Brilliant
    • , James G. Linneman
    • , Bahram Namjou
    • , Marc S. Williams
    • , Marylyn D. Ritchie
    • , Kenneth M. Borthwick
    • , Shefali S. Verma
    • , Jason H. Karnes
    • , Scott T. Weiss
    • , Thomas J. Wang
    • , C. Michael Stein
    • , Josh C. Denny
    •  & Dan M. Roden
  • Article | | open

    Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, the authors use phosphoproteomics to define kinases with distinct activity profiles in TNBC, demonstrating their prognostic value as well as their utility for simplifying TNBC classification and designing drug regimens.

    • Ivana Zagorac
    • , Sara Fernandez-Gaitero
    • , Renske Penning
    • , Harm Post
    • , Maria J. Bueno
    • , Silvana Mouron
    • , Luis Manso
    • , Manuel M. Morente
    • , Soledad Alonso
    • , Violeta Serra
    • , Javier Muñoz
    • , Gonzalo Gómez-López
    • , Jose Francisco Lopez-Acosta
    • , Veronica Jimenez-Renard
    • , Albert Gris-Oliver
    • , Fatima Al-Shahrour
    • , Elena Piñeiro-Yañez
    • , Jose Luis Montoya-Suarez
    • , Juan V. Apala
    • , Amalia Moreno-Torres
    • , Ramon Colomer
    • , Ana Dopazo
    • , Albert J. R. Heck
    • , Maarten Altelaar
    •  & Miguel Quintela-Fandino
  • Article | | open

    Little is known about the contribution of germline genetic variants to cancer drug sensitivity. Here, the authors devise an approach for joint analysis of germline variants and somatic mutations, identifying substantial germline contributions to variation in drug sensitivity.

    • Michael P. Menden
    • , Francesco Paolo Casale
    • , Johannes Stephan
    • , Graham R. Bignell
    • , Francesco Iorio
    • , Ultan McDermott
    • , Mathew J. Garnett
    • , Julio Saez-Rodriguez
    •  & Oliver Stegle
  • Article | | open

    Selection of the right cancer treatment is still a challenge. Here, the authors introduce a framework to analyze treatment benefits, using the idea that patients with similar genetic tumor profiles receiving different treatments can be used to model their responses to the alternative treatment.

    • Joske Ubels
    • , Pieter Sonneveld
    • , Erik H. van Beers
    • , Annemiek Broijl
    • , Martin H. van Vliet
    •  & Jeroen de Ridder
  • Article | | open

    Little information is available on molecular changes in response to treatment of rheumatoid arthritis (RA). Here the authors report a multi-omics study collecting patients' transcriptome, proteome, and immunophenotype data to help understand the impact of drug treatments on RA molecular phenotypes.

    • Shinya Tasaki
    • , Katsuya Suzuki
    • , Yoshiaki Kassai
    • , Masaru Takeshita
    • , Atsuko Murota
    • , Yasushi Kondo
    • , Tatsuya Ando
    • , Yusuke Nakayama
    • , Yuumi Okuzono
    • , Maiko Takiguchi
    • , Rina Kurisu
    • , Takahiro Miyazaki
    • , Keiko Yoshimoto
    • , Hidekata Yasuoka
    • , Kunihiro Yamaoka
    • , Rimpei Morita
    • , Akihiko Yoshimura
    • , Hiroyoshi Toyoshiba
    •  & Tsutomu Takeuchi
  • Article | | open

    Synthetic lethality (SL) offers a new precision oncology approach, which is based on targeting cancer-specific vulnerabilities across the whole genome, going beyond cancer drivers. The authors develop an approach termed ISLE to identify clinically relevant SL interactions and use them for patient stratification and novel target identification.

    • Joo Sang Lee
    • , Avinash Das
    • , Livnat Jerby-Arnon
    • , Rand Arafeh
    • , Noam Auslander
    • , Matthew Davidson
    • , Lynn McGarry
    • , Daniel James
    • , Arnaud Amzallag
    • , Seung Gu Park
    • , Kuoyuan Cheng
    • , Welles Robinson
    • , Dikla Atias
    • , Chani Stossel
    • , Ella Buzhor
    • , Gidi Stein
    • , Joshua J. Waterfall
    • , Paul S. Meltzer
    • , Talia Golan
    • , Sridhar Hannenhalli
    • , Eyal Gottlieb
    • , Cyril H. Benes
    • , Yardena Samuels
    • , Emma Shanks
    •  & Eytan Ruppin
  • Article | | open

    Rhinovirus (RV) infections can trigger acute exacerbations of respiratory diseases. Here, Niespodziana et al. develop a PreDicta chip that identifies the culprit RV strain from small blood samples and show that RV-A and RV-C strains are associated with most severe symptoms.

    • Katarzyna Niespodziana
    • , Katarina Stenberg-Hammar
    • , Spyridon Megremis
    • , Clarissa R. Cabauatan
    • , Kamila Napora-Wijata
    • , Phyllis C. Vacal
    • , Daniela Gallerano
    • , Christian Lupinek
    • , Daniel Ebner
    • , Thomas Schlederer
    • , Christian Harwanegg
    • , Cilla Söderhäll
    • , Marianne van Hage
    • , Gunilla Hedlin
    • , Nikolaos G. Papadopoulos
    •  & Rudolf Valenta
  • Article | | open

    High frequency oscillations (HFO) are a promising biomarker for identifying epileptogenic zones without the need to monitor spontaneous seizure episodes. Here the authors report that there is much variability in the location of HFOs offering a note of caution toward using HFO locations from short recordings as a guide for surgery.

    • Stephen V. Gliske
    • , Zachary T. Irwin
    • , Cynthia Chestek
    • , Garnett L. Hegeman
    • , Benjamin Brinkmann
    • , Oren Sagher
    • , Hugh J. L. Garton
    • , Greg A. Worrell
    •  & William C. Stacey
  • Article | | open

    FOS has been linked to bone tumour pathogenesis, and viral homologue v-fos causes osteosarcoma in mice. Here, the authors report rearrangement of FOS and its paralogue FOSB in osteoblastoma and osteoid osteoma, revealing human bone tumours that are defined by mutations of FOS and FOSB.

    • Matthew W. Fittall
    • , William Mifsud
    • , Nischalan Pillay
    • , Hongtao Ye
    • , Anna-Christina Strobl
    • , Annelien Verfaillie
    • , Jonas Demeulemeester
    • , Lei Zhang
    • , Fitim Berisha
    • , Maxime Tarabichi
    • , Matthew D. Young
    • , Elena Miranda
    • , Patrick S. Tarpey
    • , Roberto Tirabosco
    • , Fernanda Amary
    • , Agamemnon E. Grigoriadis
    • , Michael R. Stratton
    • , Peter Van Loo
    • , Cristina R. Antonescu
    • , Peter J. Campbell
    • , Adrienne M. Flanagan
    •  & Sam Behjati
  • Article | | open

    Previous studies showed that children with autism spectrum disorder (ASD) have atypicalities in the pupillary light reflex (PLR). This study uses longitudinal monitoring of infants at risk for ASD to show that PLR magnitude at 10 months of age is associated with later ASD diagnosis and symptom severity.

    • Pär Nyström
    • , Teodora Gliga
    • , Elisabeth Nilsson Jobs
    • , Gustaf Gredebäck
    • , Tony Charman
    • , Mark H. Johnson
    • , Sven Bölte
    •  & Terje Falck-Ytter
  • Article | | open

    The detection of cardiomyocyte death is a critical aspect in the diagnosis and monitoring of heart diseases. Here the authors show that cardiomyocyte-specific methylation patterns of circulating cell-free DNA may serve as a biomarker of cardiac cell death in infarcted and septic patients.

    • Hai Zemmour
    • , David Planer
    • , Judith Magenheim
    • , Joshua Moss
    • , Daniel Neiman
    • , Dan Gilon
    • , Amit Korach
    • , Benjamin Glaser
    • , Ruth Shemer
    • , Giora Landesberg
    •  & Yuval Dor
  • Review Article | | open

    This review summarizes how predictive modeling, a method that uses brain features to predict individual differences in behavior, is used to understand developmental periods. Rosenberg et al focus specifically on adolescence and examples of characteristic adolescent behaviors such as risk-taking.

    • Monica D. Rosenberg
    • , B. J. Casey
    •  & Avram J. Holmes
  • Article | | open

    Sepsis is characterized by deregulated host response to infection. Efficient therapies are still needed but a limitation for sepsis treatment is the heterogeneity in patients. Here Sweeney et al. generate prognostic models based on gene expression to improve risk stratification classification and prediction for 30-day mortality of patients.

    • Timothy E. Sweeney
    • , Thanneer M. Perumal
    • , Ricardo Henao
    • , Marshall Nichols
    • , Judith A. Howrylak
    • , Augustine M. Choi
    • , Jesús F. Bermejo-Martin
    • , Raquel Almansa
    • , Eduardo Tamayo
    • , Emma E. Davenport
    • , Katie L. Burnham
    • , Charles J. Hinds
    • , Julian C. Knight
    • , Christopher W. Woods
    • , Stephen F. Kingsmore
    • , Geoffrey S. Ginsburg
    • , Hector R. Wong
    • , Grant P. Parnell
    • , Benjamin Tang
    • , Lyle L. Moldawer
    • , Frederick E. Moore
    • , Larsson Omberg
    • , Purvesh Khatri
    • , Ephraim L. Tsalik
    • , Lara M. Mangravite
    •  & Raymond J. Langley
  • Article | | open

    Biomarkers of the tipping point before metastasis in hepatocellular carcinoma (HCC) could help stratify patient treatment. Here, the authors study dynamic network biomarkers to identify CALM3 as a potential suppressor of metastasis, the level of which can predict overall survival and relapse-free survival in postoperative HCC.

    • Biwei Yang
    • , Meiyi Li
    • , Wenqing Tang
    • , Weixin Liu
    • , Si Zhang
    • , Luonan Chen
    •  & Jinglin Xia
  • Article | | open

    Naturally acquired antibodies may inhibit Plasmodium survival in mosquitoes, alter malaria transmission dynamics, and form the basis for transmission-blocking vaccines. Here, using sera from malaria-exposed individuals, Stone et al. reveal novel antibody correlates of transmission-reducing activity.

    • Will J. R. Stone
    • , Joseph J. Campo
    • , André Lin Ouédraogo
    • , Lisette Meerstein-Kessel
    • , Isabelle Morlais
    • , Dari Da
    • , Anna Cohuet
    • , Sandrine Nsango
    • , Colin J. Sutherland
    • , Marga van de Vegte-Bolmer
    • , Rianne Siebelink-Stoter
    • , Geert-Jan van Gemert
    • , Wouter Graumans
    • , Kjerstin Lanke
    • , Adam D. Shandling
    • , Jozelyn V. Pablo
    • , Andy A. Teng
    • , Sophie Jones
    • , Roos M. de Jong
    • , Amanda Fabra-García
    • , John Bradley
    • , Will Roeffen
    • , Edwin Lasonder
    • , Giuliana Gremo
    • , Evelin Schwarzer
    • , Chris J. Janse
    • , Susheel K. Singh
    • , Michael Theisen
    • , Phil Felgner
    • , Matthias Marti
    • , Chris Drakeley
    • , Robert Sauerwein
    • , Teun Bousema
    •  & Matthijs M. Jore
  • Article | | open

    Male breast cancer (MBC) is rare and largely hormonally driven. Here, the authors examine the action of steroid hormone receptors in male and female breast cancers and find gender selective hormone receptor action that associates with the survival of MBC patients.

    • Tesa M. Severson
    • , Yongsoo Kim
    • , Stacey E. P. Joosten
    • , Karianne Schuurman
    • , Petra van der Groep
    • , Cathy B. Moelans
    • , Natalie D. ter Hoeve
    • , Quirine F. Manson
    • , John W. Martens
    • , Carolien H. M. van Deurzen
    • , Ellis Barbe
    • , Ingrid Hedenfalk
    • , Peter Bult
    • , Vincent T. H. B. M. Smit
    • , Sabine C. Linn
    • , Paul J. van Diest
    • , Lodewyk Wessels
    •  & Wilbert Zwart
  • Article | | open

    The low throughput or content of current methods for the analysis of glycans-glycan binding proteins (GBPs) interactions hampers their clinical applications. Here, the authors conjugate synthesized glycans to Luminex beads to detect GBPs and apply it for the discovery of ovarian cancer biomarkers.

    • Sharad Purohit
    • , Tiehai Li
    • , Wanyi Guan
    • , Xuezheng Song
    • , Jing Song
    • , Yanna Tian
    • , Lei Li
    • , Ashok Sharma
    • , Boying Dun
    • , David Mysona
    • , Sharad Ghamande
    • , Bunja Rungruang
    • , Richard D. Cummings
    • , Peng George Wang
    •  & Jin-Xiong She
  • Article | | open

    The extracellular matrix is under variable strain, but we lack the tools to detect differences in strain. Here the authors develop a probe based on a bacterial fibronectin-binding peptide that binds to relaxed fibronectin fibrils and detects relaxed matrix in cell culture, tissue slices and in vivo.

    • Simon Arnoldini
    • , Alessandra Moscaroli
    • , Mamta Chabria
    • , Manuel Hilbert
    • , Samuel Hertig
    • , Roger Schibli
    • , Martin Béhé
    •  & Viola Vogel
  • Article | | open

    The authors use an integrative clustering approach to identify two laryngeal cancer clusters with distinct prognosis and show that mutations damaging the NSD1 and NSD2 methyltransferases segregate to the cluster with favorable prognosis, and independently predict longer survival in patients with laryngeal, but not other head and neck cancers.

    • Suraj Peri
    • , Evgeny Izumchenko
    • , Adrian D. Schubert
    • , Michael J. Slifker
    • , Karen Ruth
    • , Ilya G. Serebriiskii
    • , Theresa Guo
    • , Barbara A. Burtness
    • , Ranee Mehra
    • , Eric A. Ross
    • , David Sidransky
    •  & Erica A. Golemis
  • Article | | open

    The current FDA-approved whole blood stabilization method for circulating tumor cell (CTC) isolation suffers from RNA degradation. Here the authors combine hypothermic preservation and antiplatelet strategies to stabilize whole blood up to 72 h without compromising CTC yield and RNA integrity.

    • Keith H. K. Wong
    • , Shannon N. Tessier
    • , David T. Miyamoto
    • , Kathleen L. Miller
    • , Lauren D. Bookstaver
    • , Thomas R. Carey
    • , Cleo J. Stannard
    • , Vishal Thapar
    • , Eric C. Tai
    • , Kevin D. Vo
    • , Erin S. Emmons
    • , Haley M. Pleskow
    • , Rebecca D. Sandlin
    • , Lecia V. Sequist
    • , David T. Ting
    • , Daniel A. Haber
    • , Shyamala Maheswaran
    • , Shannon L. Stott
    •  & Mehmet Toner
  • Article | | open

    Multiple myeloma is characterized by high rates of drug resistance and relapse. Here the authors utilize a functional assay to assess the ex vivo drug sensitivity of single multiple myeloma cells based on measuring the mass accumulation rate of individual cells.

    • Arif E. Cetin
    • , Mark M. Stevens
    • , Nicholas L. Calistri
    • , Mariateresa Fulciniti
    • , Selim Olcum
    • , Robert J. Kimmerling
    • , Nikhil C. Munshi
    •  & Scott R. Manalis
  • Article | | open

    CD4+ T cells secreting interleukin-17 (TH17) have diverse functions in modulating autoimmune diseases. Here the authors show via transcriptome analyses that a subset of human TH 17 co-expressing interferon-γ (TH1/17) has a molecular signature similar to “pathogenic” mouse TH 17 but distinct from “non-pathogenic” mouse TH 17.

    • Dan Hu
    • , Samuele Notarbartolo
    • , Tom Croonenborghs
    • , Bonny Patel
    • , Ron Cialic
    • , Tun-Hsiang Yang
    • , Dominik Aschenbrenner
    • , Karin M. Andersson
    • , Marco Gattorno
    • , Minh Pham
    • , Pia Kivisakk
    • , Isabelle V. Pierre
    • , Youjin Lee
    • , Karun Kiani
    • , Maria Bokarewa
    • , Emily Tjon
    • , Nathalie Pochet
    • , Federica Sallusto
    • , Vijay K. Kuchroo
    •  & Howard L. Weiner
  • Article | | open

    Abnormal levels of Aβ42 in the cerebrospinal fluid occur prior to a positive amyloid PET scan in the brain of individuals with Alzheimer’s disease and here the authors use this temporal pattern to identify individuals with very early stage AD. They show that Aβ fibrils start to accumulate in some of the regions of the default mode network and affect brain connectivity before neurodegeneration occurs.

    • Sebastian Palmqvist
    • , Michael Schöll
    • , Olof Strandberg
    • , Niklas Mattsson
    • , Erik Stomrud
    • , Henrik Zetterberg
    • , Kaj Blennow
    • , Susan Landau
    • , William Jagust
    •  & Oskar Hansson
  • Article | | open

    Liver mitochondrial metabolism plays an important role for glucose and lipid homeostasis and its alterations contribute to metabolic disorders, including fatty liver and diabetes. Here Perry et al. develop a method for the measurement of hepatic fluxes by using lactate and glucose tracers in combination with NMR spectroscopy.

    • Rachel J. Perry
    • , Liang Peng
    • , Gary W. Cline
    • , Gina M. Butrico
    • , Yongliang Wang
    • , Xian-Man Zhang
    • , Douglas L. Rothman
    • , Kitt Falk Petersen
    •  & Gerald I. Shulman
  • Article | | open

    In prostate cancer, the role of mutations in the maternally-inherited mitochondrial genome are not well known. Here, the authors demonstrate frequent, age-dependent mitochondrial mutation in prostate cancer. Strong links between mitochondrial and nuclear mutational profiles are associated with clinical aggressivity.

    • Julia F. Hopkins
    • , Veronica Y. Sabelnykova
    • , Joachim Weischenfeldt
    • , Ronald Simon
    • , Jennifer A. Aguiar
    • , Rached Alkallas
    • , Lawrence E. Heisler
    • , Junyan Zhang
    • , John D. Watson
    • , Melvin L. K. Chua
    • , Michael Fraser
    • , Francesco Favero
    • , Chris Lawerenz
    • , Christoph Plass
    • , Guido Sauter
    • , John D. McPherson
    • , Theodorus van der Kwast
    • , Jan Korbel
    • , Thorsten Schlomm
    • , Robert G. Bristow
    •  & Paul C. Boutros
  • Article | | open

    Caloric restriction has been shown to increase lifespan in mammals. Here, the authors provide evidence that age-related methylation drift correlates with lifespan and that caloric restriction in mice and rhesus monkeys results in attenuation of age-related methylation drift.

    • Shinji Maegawa
    • , Yue Lu
    • , Tomomitsu Tahara
    • , Justin T. Lee
    • , Jozef Madzo
    • , Shoudan Liang
    • , Jaroslav Jelinek
    • , Ricki J. Colman
    •  & Jean-Pierre J. Issa
  • Article | | open

    Oral squamous cell carcinoma is a prevalent malignancy in Taiwan. Here, the authors show that OSCC in Taiwanese show a frequent deletion polymorphism in the cytidine deaminases gene cluster APOBEC3 resulting in increased expression of A3A, which is shown to be of clinical prognostic relevance.

    • Ting-Wen Chen
    • , Chi-Ching Lee
    • , Hsuan Liu
    • , Chi-Sheng Wu
    • , Curtis R. Pickering
    • , Po-Jung Huang
    • , Jing Wang
    • , Ian Yi-Feng Chang
    • , Yuan-Ming Yeh
    • , Chih-De Chen
    • , Hsin-Pai Li
    • , Ji-Dung Luo
    • , Bertrand Chin-Ming Tan
    • , Timothy En Haw Chan
    • , Chuen Hsueh
    • , Lichieh Julie Chu
    • , Yi-Ting Chen
    • , Bing Zhang
    • , Chia-Yu Yang
    • , Chih-Ching Wu
    • , Chia-Wei Hsu
    • , Lai-Chu See
    • , Petrus Tang
    • , Jau-Song Yu
    • , Wei-Chao Liao
    • , Wei-Fan Chiang
    • , Henry Rodriguez
    • , Jeffrey N. Myers
    • , Kai-Ping Chang
    •  & Yu-Sun Chang
  • Article | | open

    Real-time monitoring of phosphate metabolism and distribution in the live body without ionizing radiation is highly desirable. Here, the authors show dissolution-dynamic nuclear polarization technology can enable nuclear magnetic resonance detection of hyperpolarized 31P of important biological phosphates in aqueous solutions.

    • Atara Nardi-Schreiber
    • , Ayelet Gamliel
    • , Talia Harris
    • , Gal Sapir
    • , Jacob Sosna
    • , J. Moshe Gomori
    •  & Rachel Katz-Brull
  • Article | | open

    Early detection of gum inflammation caused by dental implants helps prevent tissue damage. Here, the authors present a peptide sensor that generates a bitter taste when cleaved by proteases present in peri-implant disease, embed it in a chewing gum, and compare the probe to existing sensors using patient saliva.

    • J. Ritzer
    • , T. Lühmann
    • , C. Rode
    • , M. Pein-Hackelbusch
    • , I. Immohr
    • , U. Schedler
    • , T. Thiele
    • , S. Stübinger
    • , B. v. Rechenberg
    • , J. Waser-Althaus
    • , F. Schlottig
    • , M. Merli
    • , H. Dawe
    • , M. Karpíšek
    • , R. Wyrwa
    • , M. Schnabelrauch
    •  & L. Meinel
  • Article | | open

    Preparation of samples for diagnosis can affect the detection of biomarkers and metabolites. Here, the authors use a silver nanoparticle plasmonics approach for the detection of biomarkers in patients as well as investigate the distribution of drugs in serum and cerebral spinal fluid.

    • Lin Huang
    • , Jingjing Wan
    • , Xiang Wei
    • , Yu Liu
    • , Jingyi Huang
    • , Xuming Sun
    • , Ru Zhang
    • , Deepanjali D. Gurav
    • , Vadanasundari Vedarethinam
    • , Yan Li
    • , Ruoping Chen
    •  & Kun Qian
  • Article | | open

    Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

    • M. Carola Zillikens
    • , Serkalem Demissie
    • , Yi-Hsiang Hsu
    • , Laura M. Yerges-Armstrong
    • , Wen-Chi Chou
    • , Lisette Stolk
    • , Gregory Livshits
    • , Linda Broer
    • , Toby Johnson
    • , Daniel L. Koller
    • , Zoltán Kutalik
    • , Jian’an Luan
    • , Ida Malkin
    • , Janina S. Ried
    • , Albert V. Smith
    • , Gudmar Thorleifsson
    • , Liesbeth Vandenput
    • , Jing Hua Zhao
    • , Weihua Zhang
    • , Ali Aghdassi
    • , Kristina Åkesson
    • , Najaf Amin
    • , Leslie J. Baier
    • , Inês Barroso
    • , David A. Bennett
    • , Lars Bertram
    • , Rainer Biffar
    • , Murielle Bochud
    • , Michael Boehnke
    • , Ingrid B. Borecki
    • , Aron S. Buchman
    • , Liisa Byberg
    • , Harry Campbell
    • , Natalia Campos Obanda
    • , Jane A. Cauley
    • , Peggy M. Cawthon
    • , Henna Cederberg
    • , Zhao Chen
    • , Nam H. Cho
    • , Hyung Jin Choi
    • , Melina Claussnitzer
    • , Francis Collins
    • , Steven R. Cummings
    • , Philip L. De Jager
    • , Ilja Demuth
    • , Rosalie A. M. Dhonukshe-Rutten
    • , Luda Diatchenko
    • , Gudny Eiriksdottir
    • , Anke W. Enneman
    • , Mike Erdos
    • , Johan G. Eriksson
    • , Joel Eriksson
    • , Karol Estrada
    • , Daniel S. Evans
    • , Mary F. Feitosa
    • , Mao Fu
    • , Melissa Garcia
    • , Christian Gieger
    • , Thomas Girke
    • , Nicole L. Glazer
    • , Harald Grallert
    • , Jagvir Grewal
    • , Bok-Ghee Han
    • , Robert L. Hanson
    • , Caroline Hayward
    • , Albert Hofman
    • , Eric P. Hoffman
    • , Georg Homuth
    • , Wen-Chi Hsueh
    • , Monica J. Hubal
    • , Alan Hubbard
    • , Kim M. Huffman
    • , Lise B. Husted
    • , Thomas Illig
    • , Erik Ingelsson
    • , Till Ittermann
    • , John-Olov Jansson
    • , Joanne M. Jordan
    • , Antti Jula
    • , Magnus Karlsson
    • , Kay-Tee Khaw
    • , Tuomas O. Kilpeläinen
    • , Norman Klopp
    • , Jacqueline S. L. Kloth
    • , Heikki A. Koistinen
    • , William E. Kraus
    • , Stephen Kritchevsky
    • , Teemu Kuulasmaa
    • , Johanna Kuusisto
    • , Markku Laakso
    • , Jari Lahti
    • , Thomas Lang
    • , Bente L. Langdahl
    • , Lenore J. Launer
    • , Jong-Young Lee
    • , Markus M. Lerch
    • , Joshua R. Lewis
    • , Lars Lind
    • , Cecilia Lindgren
    • , Yongmei Liu
    • , Tian Liu
    • , Youfang Liu
    • , Östen Ljunggren
    • , Mattias Lorentzon
    • , Robert N. Luben
    • , William Maixner
    • , Fiona E. McGuigan
    • , Carolina Medina-Gomez
    • , Thomas Meitinger
    • , Håkan Melhus
    • , Dan Mellström
    • , Simon Melov
    • , Karl Michaëlsson
    • , Braxton D. Mitchell
    • , Andrew P. Morris
    • , Leif Mosekilde
    • , Anne Newman
    • , Carrie M. Nielson
    • , Jeffrey R. O’Connell
    • , Ben A. Oostra
    • , Eric S. Orwoll
    • , Aarno Palotie
    • , Stephen C. J. Parker
    • , Munro Peacock
    • , Markus Perola
    • , Annette Peters
    • , Ozren Polasek
    • , Richard L. Prince
    • , Katri Räikkönen
    • , Stuart H. Ralston
    • , Samuli Ripatti
    • , John A. Robbins
    • , Jerome I. Rotter
    • , Igor Rudan
    • , Veikko Salomaa
    • , Suzanne Satterfield
    • , Eric E. Schadt
    • , Sabine Schipf
    • , Laura Scott
    • , Joban Sehmi
    • , Jian Shen
    • , Chan Soo Shin
    • , Gunnar Sigurdsson
    • , Shad Smith
    • , Nicole Soranzo
    • , Alena Stančáková
    • , Elisabeth Steinhagen-Thiessen
    • , Elizabeth A. Streeten
    • , Unnur Styrkarsdottir
    • , Karin M. A. Swart
    • , Sian-Tsung Tan
    • , Mark A. Tarnopolsky
    • , Patricia Thompson
    • , Cynthia A. Thomson
    • , Unnur Thorsteinsdottir
    • , Emmi Tikkanen
    • , Gregory J. Tranah
    • , Jaakko Tuomilehto
    • , Natasja M. van Schoor
    • , Arjun Verma
    • , Peter Vollenweider
    • , Henry Völzke
    • , Jean Wactawski-Wende
    • , Mark Walker
    • , Michael N. Weedon
    • , Ryan Welch
    • , H.-Erich Wichmann
    • , Elisabeth Widen
    • , Frances M. K. Williams
    • , James F. Wilson
    • , Nicole C. Wright
    • , Weijia Xie
    • , Lei Yu
    • , Yanhua Zhou
    • , John C. Chambers
    • , Angela Döring
    • , Cornelia M. van Duijn
    • , Michael J. Econs
    • , Vilmundur Gudnason
    • , Jaspal S. Kooner
    • , Bruce M. Psaty
    • , Timothy D. Spector
    • , Kari Stefansson
    • , Fernando Rivadeneira
    • , André G. Uitterlinden
    • , Nicholas J. Wareham
    • , Vicky Ossowski
    • , Dawn Waterworth
    • , Ruth J. F. Loos
    • , David Karasik
    • , Tamara B. Harris
    • , Claes Ohlsson
    •  & Douglas P. Kiel
  • Article | | open

    Predicting the hepatotoxic effects of new drugs is still a challenge. Using toxicogenomics data, the authors here define a predictive toxicogenomic space (PTGS), the component gene space capturing dose-dependent cytotoxicity, and demonstrate that it can be used to accurately predict drug-induced liver pathology, including human drug-induced liver injury from in vitro data.

    • Pekka Kohonen
    • , Juuso A. Parkkinen
    • , Egon L. Willighagen
    • , Rebecca Ceder
    • , Krister Wennerberg
    • , Samuel Kaski
    •  & Roland C. Grafström
  • Article | | open

    Sleep patterns vary and are associated with health and disease. Here Purcell et al characterize sleep spindle activity in 11,630 individuals and describe age-related changes, genetic influences, and possible confounding effects, serving as a resource for further understanding the physiology of sleep.

    • S. M. Purcell
    • , D. S. Manoach
    • , C. Demanuele
    • , B. E. Cade
    • , S. Mariani
    • , R. Cox
    • , G. Panagiotaropoulou
    • , R. Saxena
    • , J. Q. Pan
    • , J. W. Smoller
    • , S. Redline
    •  & R. Stickgold
  • Article | | open

    Cancer cells adapt to the changing microenvironment by activating different pathways through multiple mechanisms. Here the authors identify long noncoding RNA MIR31HG as a HIF-1α co-activator required for the induction of the hypoxic response and show its oncogenic role in oral carcinogenesis.

    • Jing-Wen Shih
    • , Wei-Fan Chiang
    • , Alexander T. H. Wu
    • , Ming-Heng Wu
    • , Ling-Yu Wang
    • , Yen-Ling Yu
    • , Yu-Wen Hung
    • , Wen-Chang Wang
    • , Cheng-Ying Chu
    • , Chiu-Lien Hung
    • , Chun A. Changou
    • , Yun Yen
    •  & Hsing-Jien Kung