Articles

T cell dynamics and response of the microbiota after gene therapy to treat X-linked severe combined immunodeficiency

Mutation of the IL2RG gene results in a form of severe combined immune deficiency (SCID-X1), which has been treated successfully with hematopoietic stem cell gene therapy. SCID-X1 gene therapy results in reconsti...

Authors: Erik L. Clarke, A. Jesse Connell, Emmanuelle Six, Nadia A. Kadry, Arwa A. Abbas, Young Hwang, John K. Everett, Casey E. Hofstaedter, Rebecca Marsh, Myriam Armant, Judith Kelsen, Luigi D. Notarangelo, Ronald G. Collman, Salima Hacein-Bey-Abina, Donald B. Kohn, Marina Cavazzana…

Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder

Exome sequencing is now being incorporated into clinical care for pediatric and adult populations, but its integration into prenatal diagnosis has been more limited. One reason for this is the paucity of infor...

Authors: Elizabeth A. Normand, Alicia Braxton, Salma Nassef, Patricia A. Ward, Francesco Vetrini, Weimin He, Vipulkumar Patel, Chunjing Qu, Lauren E. Westerfield, Samantha Stover, Avinash V. Dharmadhikari, Donna M. Muzny, Richard A. Gibbs, Hongzheng Dai, Linyan Meng, Xia Wang…

Advanced model systems and tools for basic and translational human immunology

There are fundamental differences between humans and the animals we typically use to study the immune system. We have learned much from genetically manipulated and inbred animal models, but instances in which ...

Authors: Lisa E. Wagar, Robert M. DiFazio and Mark M. Davis

Infection and immunity: insights and therapeutic strategies through genomic analysis of the host, pathogen, and host–pathogen interaction

Authors: Julia Simundza

Single-cell transcriptomics reveal that PD-1 mediates immune tolerance by regulating proliferation of regulatory T cells

We have previously reported an antigen-specific protocol to induce transplant tolerance and linked suppression to human embryonic stem cell (hESC)-derived tissues in immunocompetent mice through coreceptor and...

Authors: Cherry S. Leung, Kevin Y. Yang, Xisheng Li, Vicken W. Chan, Manching Ku, Herman Waldmann, Shohei Hori, Jason C. H. Tsang, Yuk Ming Dennis Lo and Kathy O. Lui

Exome-wide analysis of bi-allelic alterations identifies a Lynch phenotype in The Cancer Genome Atlas

Cancer susceptibility germline variants generally require somatic alteration of the remaining allele to drive oncogenesis and, in some cases, tumor mutational profiles. Whether combined germline and somatic bi...

Authors: Alexandra R. Buckley, Trey Ideker, Hannah Carter, Olivier Harismendy and Nicholas J. Schork

Increased DNA methylation variability in rheumatoid arthritis-discordant monozygotic twins

Rheumatoid arthritis is a common autoimmune disorder influenced by both genetic and environmental factors. Epigenome-wide association studies can identify environmentally mediated epigenetic changes such as al...

Authors: Amy P. Webster, Darren Plant, Simone Ecker, Flore Zufferey, Jordana T. Bell, Andrew Feber, Dirk S. Paul, Stephan Beck, Anne Barton, Frances M. K. Williams and Jane Worthington

Comprehensive antibiotic-linked mutation assessment by resistance mutation sequencing (RM-seq)

Mutation acquisition is a major mechanism of bacterial antibiotic resistance that remains insufficiently characterised. Here we present RM-seq, a new amplicon-based deep sequencing workflow based on a molecula...

Authors: Romain Guérillot, Lucy Li, Sarah Baines, Brian Howden, Mark B. Schultz, Torsten Seemann, Ian Monk, Sacha J. Pidot, Wei Gao, Stefano Giulieri, Anders Gonçalves da Silva, Anthony D’Agata, Takehiro Tomita, Anton Y. Peleg, Timothy P. Stinear and Benjamin P. Howden

Exploring the pre-immune landscape of antigen-specific T cells

Adaptive immune responses to newly encountered pathogens depend on the mobilization of antigen-specific clonotypes from a vastly diverse pool of naive T cells. Using recent advances in immune repertoire sequen...

Authors: Mikhail V. Pogorelyy, Alla D. Fedorova, James E. McLaren, Kristin Ladell, Dmitri V. Bagaev, Alexey V. Eliseev, Artem I. Mikelov, Anna E. Koneva, Ivan V. Zvyagin, David A. Price, Dmitry M. Chudakov and Mikhail Shugay

Genomic exploration of sequential clinical isolates reveals a distinctive molecular signature of persistent Staphylococcus aureus bacteraemia

Large-scale genomic studies of within-host diversity in Staphylococcus aureus bacteraemia (SAB) are needed to understanding bacterial adaptation underlying persistence and thus refining the role of genomics in ma...

Authors: Stefano G. Giulieri, Sarah L. Baines, Romain Guerillot, Torsten Seemann, Anders Gonçalves da Silva, Mark Schultz, Ruth C. Massey, Natasha E. Holmes, Timothy P. Stinear and Benjamin P. Howden

Cross-genetic determination of maternal and neonatal immune mediators during pregnancy

The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as...

Authors: Michela Traglia, Lisa A. Croen, Karen L. Jones, Luke S. Heuer, Robert Yolken, Martin Kharrazi, Gerald N. DeLorenze, Paul Ashwood, Judy Van de Water and Lauren A. Weiss

p53 activation: a checkpoint for precision genome editing?

Recent work has reported that the activation of the p53 pathway in primary cells hampers the efficiency of genome editing by CRISPR/Cas9 via induction of apoptosis or cell cycle arrest. These findings highligh...

Authors: Anastasia Conti and Raffaella Di Micco

A genome-wide siRNA screen identifies a druggable host pathway essential for the Ebola virus life cycle

The 2014–2016 Ebola virus (EBOV) outbreak in West Africa highlighted the need for improved therapeutic options against this virus. Approaches targeting host factors/pathways essential for the virus are advanta...

Authors: Scott Martin, Abhilash I. Chiramel, Marie Luisa Schmidt, Yu-Chi Chen, Nadia Whitt, Ari Watt, Eric C. Dunham, Kyle Shifflett, Shelby Traeger, Anne Leske, Eugen Buehler, Cynthia Martellaro, Janine Brandt, Lisa Wendt, Andreas Müller, Stephanie Peitsch…

Exploring the OncoGenomic Landscape of cancer

The widespread incorporation of next-generation sequencing into clinical oncology has yielded an unprecedented amount of molecular data from thousands of patients. A main current challenge is to find out relia...

Authors: Lidia Mateo, Oriol Guitart-Pla, Miquel Duran-Frigola and Patrick Aloy

Causality in dietary interventions—building a case for gut microbiota

We provide a conceptual framework to establish a causal link between diet, gut microbiota, and health. Identifying the key strains that mediate microbe–host interactions and understanding the mechanisms involv...

Authors: Yan Y. Lam, Chenhong Zhang and Liping Zhao

Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines

Humoral immune responses to infectious agents or vaccination vary substantially among individuals, and many of the factors responsible for this variability remain to be defined. Current evidence suggests that ...

Authors: Petar Scepanovic, Cécile Alanio, Christian Hammer, Flavia Hodel, Jacob Bergstedt, Etienne Patin, Christian W. Thorball, Nimisha Chaturvedi, Bruno Charbit, Laurent Abel, Lluis Quintana-Murci, Darragh Duffy, Matthew L. Albert and Jacques Fellay

Integrative omics analyses broaden treatment targets in human cancer

Although large-scale, next-generation sequencing (NGS) studies of cancers hold promise for enabling precision oncology, challenges remain in integrating NGS with clinically validated biomarkers.

Authors: Sohini Sengupta, Sam Q. Sun, Kuan-lin Huang, Clara Oh, Matthew H. Bailey, Rajees Varghese, Matthew A. Wyczalkowski, Jie Ning, Piyush Tripathi, Joshua F. McMichael, Kimberly J. Johnson, Cyriac Kandoth, John Welch, Cynthia Ma, Michael C. Wendl, Samuel H. Payne…

Single-cell transcriptome analysis of lineage diversity in high-grade glioma

Despite extensive molecular characterization, we lack a comprehensive understanding of lineage identity, differentiation, and proliferation in high-grade gliomas (HGGs).

Authors: Jinzhou Yuan, Hanna Mendes Levitin, Veronique Frattini, Erin C. Bush, Deborah M. Boyett, Jorge Samanamud, Michele Ceccarelli, Athanassios Dovas, George Zanazzi, Peter Canoll, Jeffrey N. Bruce, Anna Lasorella, Antonio Iavarone and Peter A. Sims

Rare variants in SOX17 are associated with pulmonary arterial hypertension with congenital heart disease

Pulmonary arterial hypertension (PAH) is a rare disease characterized by distinctive changes in pulmonary arterioles that lead to progressive pulmonary arterial pressures, right-sided heart failure, and a high...

Authors: Na Zhu, Carrie L. Welch, Jiayao Wang, Philip M. Allen, Claudia Gonzaga-Jauregui, Lijiang Ma, Alejandra K. King, Usha Krishnan, Erika B. Rosenzweig, D. Dunbar Ivy, Eric D. Austin, Rizwan Hamid, Michael W. Pauciulo, Katie A. Lutz, William C. Nichols, Jeffrey G. Reid…

Functional and genomic analyses reveal therapeutic potential of targeting β-catenin/CBP activity in head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy characterized by tumor heterogeneity, locoregional metastases, and resistance to existing treatments. Although a number of genomic and ...

Authors: Vinay K. Kartha, Khalid A. Alamoud, Khikmet Sadykov, Bach-Cuc Nguyen, Fabrice Laroche, Hui Feng, Jina Lee, Sara I. Pai, Xaralabos Varelas, Ann Marie Egloff, Jennifer E. Snyder-Cappione, Anna C. Belkina, Manish V. Bais, Stefano Monti and Maria A. Kukuruzinska

Epigenomic profiling of non-small cell lung cancer xenografts uncover LRP12 DNA methylation as predictive biomarker for carboplatin resistance

Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related deaths worldwide and is primarily treated with radiation, surgery, and platinum-based drugs like cisplatin and carboplatin. The maj...

Authors: Sabrina Grasse, Matthias Lienhard, Steffen Frese, Martin Kerick, Anne Steinbach, Christina Grimm, Michelle Hussong, Jana Rolff, Michael Becker, Felix Dreher, Uwe Schirmer, Stefan Boerno, Anna Ramisch, Gunda Leschber, Bernd Timmermann, Christian Grohé…

Prioritization and functional assessment of noncoding variants associated with complex diseases

Unraveling functional noncoding variants associated with complex diseases is still a great challenge. We present a novel algorithm, Prioritization And Functional Assessment (PAFA), that prioritizes and assesse...

Authors: Lin Zhou and Fangqing Zhao

Exploration of Plasmodium vivax transmission dynamics and recurrent infections in the Peruvian Amazon using whole genome sequencing

Plasmodium vivax poses a significant challenge to malaria elimination due to its ability to cause relapsed infections from reactivation of dormant liver parasites called hypnozoites. We analyzed 69 P. vivax whole...

Authors: Annie N. Cowell, Hugo O. Valdivia, Danett K. Bishop and Elizabeth A. Winzeler

INSaFLU: an automated open web-based bioinformatics suite “from-reads” for influenza whole-genome-sequencing-based surveillance

A new era of flu surveillance has already started based on the genetic characterization and exploration of influenza virus evolution at whole-genome scale. Although this has been prioritized by national and in...

Authors: Vítor Borges, Miguel Pinheiro, Pedro Pechirra, Raquel Guiomar and João Paulo Gomes

Red blood cell indices and anaemia as causative factors for cognitive function deficits and for Alzheimer’s disease

Studies have shown that low haemoglobin and anaemia are associated with poor cognition, and anaemia is known to be associated with Alzheimer’s disease (AD), but the mechanism of this risk is unknown. Here, we ...

Authors: Laura M. Winchester, John Powell, Simon Lovestone and Alejo J. Nevado-Holgado

Disease-specific regulation of gene expression in a comparative analysis of juvenile idiopathic arthritis and inflammatory bowel disease

The genetic and immunological factors that contribute to differences in susceptibility and progression between sub-types of inflammatory and autoimmune diseases continue to be elucidated. Inflammatory bowel di...

Authors: Angela Mo, Urko M. Marigorta, Dalia Arafat, Lai Hin Kimi Chan, Lori Ponder, Se Ryeong Jang, Jarod Prince, Subra Kugathasan, Sampath Prahalad and Greg Gibson

Therapy-induced stress response is associated with downregulation of pre-mRNA splicing in cancer cells

Abnormal pre-mRNA splicing regulation is common in cancer, but the effects of chemotherapy on this process remain unclear.

Authors: Ksenia S. Anufrieva, Victoria О. Shender, Georgij P. Arapidi, Marat S. Pavlyukov, Michail I. Shakhparonov, Polina V. Shnaider, Ivan O. Butenko, Maria A. Lagarkova and Vadim M. Govorun

Genomic surveillance of avian-origin influenza A viruses causing human disease

Avian influenza A viruses (AIVs) pose a threat to global health because of their sporadic zoonotic transmission and potential to cause pandemics. Genomic surveillance of AIVs has become a powerful, cost-effect...

Authors: Tommy T. Lam and Oliver G. Pybus

Developing Zika vaccines: the lessons for disease X

There is an urgent need to develop vaccines against emerging diseases, including those caused by pathogens that are currently unknown to cause human disease, termed ‘disease X’. Here, Zika virus infection is c...

Authors: Alan D. T. Barrett

KLRD1-expressing natural killer cells predict influenza susceptibility

Influenza infects tens of millions of people every year in the USA. Other than notable risk groups, such as children and the elderly, it is difficult to predict what subpopulations are at higher risk of infect...

Authors: Erika Bongen, Francesco Vallania, Paul J. Utz and Purvesh Khatri

Genetic variants associated with Alzheimer’s disease confer different cerebral cortex cell-type population structure

Alzheimer’s disease (AD) is characterized by neuronal loss and astrocytosis in the cerebral cortex. However, the specific effects that pathological mutations and coding variants associated with AD have on the ...

Authors: Zeran Li, Jorge L. Del-Aguila, Umber Dube, John Budde, Rita Martinez, Kathleen Black, Qingli Xiao, Nigel J. Cairns, Joseph D. Dougherty, Jin-Moo Lee, John C. Morris, Randall J. Bateman, Celeste M. Karch, Carlos Cruchaga and Oscar Harari

A computational tool to detect DNA alterations tailored to formalin-fixed paraffin-embedded samples in cancer clinical sequencing

Advanced cancer genomics technologies are now being employed in clinical sequencing, where next-generation sequencers are used to simultaneously identify multiple types of DNA alterations for prescription of m...

Authors: Mamoru Kato, Hiromi Nakamura, Momoko Nagai, Takashi Kubo, Asmaa Elzawahry, Yasushi Totoki, Yuko Tanabe, Eisaku Furukawa, Joe Miyamoto, Hiromi Sakamoto, Shingo Matsumoto, Kuniko Sunami, Yasuhito Arai, Yutaka Suzuki, Teruhiko Yoshida, Katsuya Tsuchihara…

PanDrugs: a novel method to prioritize anticancer drug treatments according to individual genomic data

Large-sequencing cancer genome projects have shown that tumors have thousands of molecular alterations and their frequency is highly heterogeneous. In such scenarios, physicians and oncologists routinely face ...

Authors: Elena Piñeiro-Yáñez, Miguel Reboiro-Jato, Gonzalo Gómez-López, Javier Perales-Patón, Kevin Troulé, José Manuel Rodríguez, Héctor Tejero, Takeshi Shimamura, Pedro Pablo López-Casas, Julián Carretero, Alfonso Valencia, Manuel Hidalgo, Daniel Glez-Peña and Fátima Al-Shahrour

Rare copy number variants analysis identifies novel candidate genes in heterotaxy syndrome patients with congenital heart defects

Heterotaxy (Htx) syndrome comprises a class of congenital disorders resulting from malformations in left-right body patterning. Approximately 90% of patients with heterotaxy have serious congenital heart disea...

Authors: Chunjie Liu, Ruixue Cao, Yuejuan Xu, Tingting Li, Fen Li, Sun Chen, Rang Xu and Kun Sun

Integrative analysis of DNA methylation and gene expression reveals hepatocellular carcinoma-specific diagnostic biomarkers

Hepatocellular carcinoma (HCC) is the one of the most common cancers and lethal diseases in the world. DNA methylation alteration is frequently observed in HCC and may play important roles in carcinogenesis an...

Authors: Jinming Cheng, Dongkai Wei, Yuan Ji, Lingli Chen, Liguang Yang, Guang Li, Leilei Wu, Ting Hou, Lu Xie, Guohui Ding, Hong Li and Yixue Li

Antifungal immune responses: emerging host–pathogen interactions and translational implications

Understanding the complex and highly dynamic interactions between fungi and host cells in a tissue-specific manner is crucial to facilitate the development of new therapeutic approaches to infections. Here, we...

Authors: Vinod Kumar, Frank L. van de Veerdonk and Mihai G. Netea

Getting up close and personal with UK genomics and beyond

Stephan Beck discusses recent developments in sharing personal genomes as part of the Personal Genome Project in the UK and globally, and how these efforts are advancing research.

Authors: Stephan Beck

Integrated time course omics analysis distinguishes immediate therapeutic response from acquired resistance

Targeted therapies specifically act by blocking the activity of proteins that are encoded by genes critical for tumorigenesis. However, most cancers acquire resistance and long-term disease remission is rarely...

Authors: Genevieve Stein-O’Brien, Luciane T. Kagohara, Sijia Li, Manjusha Thakar, Ruchira Ranaweera, Hiroyuki Ozawa, Haixia Cheng, Michael Considine, Sandra Schmitz, Alexander V. Favorov, Ludmila V. Danilova, Joseph A. Califano, Evgeny Izumchenko, Daria A. Gaykalova, Christine H. Chung and Elana J. Fertig

Beating the odds: programming proliferation in the mammalian heart

The heart is one of the least regenerative organs in the human body; adult cardiac myocytes divide at extremely low frequency. Therefore, meaningful induction of cardiac regeneration requires in-depth understa...

Authors: Rajan Jain, Andrey Poleshko and Jonathan A. Epstein

Correction to: Differential analysis between somatic mutation and germline variation profiles reveals cancer-related genes

Due to an error introduced during copyediting of this article [1], reference [8] incorrectly reads

Authors: Pawel F. Przytycki and Mona Singh

Simple paired heavy- and light-chain antibody repertoire sequencing using endoplasmic reticulum microsomes

Existing methods for paired antibody heavy- and light-chain repertoire sequencing rely on specialized equipment and are limited by their commercial availability and high costs. Here, we report a novel simple a...

Authors: Praneeth Reddy Devulapally, Jörg Bürger, Thorsten Mielke, Zoltán Konthur, Hans Lehrach, Marie-Laure Yaspo, Jörn Glökler and Hans-Jörg Warnatz

MutationalPatterns: comprehensive genome-wide analysis of mutational processes

Base substitution catalogues represent historical records of mutational processes that have been active in a cell. Such processes can be distinguished by various characteristics, like mutation type, sequence c...

Authors: Francis Blokzijl, Roel Janssen, Ruben van Boxtel and Edwin Cuppen

Pathogen detection in the CRISPR–Cas era

CRISPR–Cas systems have provided revolutionary tools for genome editing. The discovery of Cas proteins with alternative activities has now enabled sensitive and robust tools for detecting nucleic acids. Recent...

Authors: Dipali G. Sashital

Enabling multiplexed testing of pooled donor cells through whole-genome sequencing

We describe a method that enables the multiplex screening of a pool of many different donor cell lines. Our method accurately predicts each donor proportion from the pool without requiring the use of unique DN...

Authors: Yingleong Chan, Ying Kai Chan, Daniel B. Goodman, Xiaoge Guo, Alejandro Chavez, Elaine T. Lim and George M. Church

Integrative analysis reveals functional and regulatory roles of H3K79me2 in mediating alternative splicing

Accumulating evidence suggests alternative splicing (AS) is a co-transcriptional splicing process not only controlled by RNA-binding splicing factors, but also mediated by epigenetic regulators, such as chroma...

Authors: Tianbao Li, Qi Liu, Nick Garza, Steven Kornblau and Victor X. Jin

Sensitivity to sequencing depth in single-cell cancer genomics

Querying cancer genomes at single-cell resolution is expected to provide a powerful framework to understand in detail the dynamics of cancer evolution. However, given the high costs currently associated with s...

Authors: João M. Alves and David Posada

Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development

The interplay of epigenetic processes and the intestinal microbiota may play an important role in intestinal development and homeostasis. Previous studies have established that the microbiota regulates a large...

Authors: Wei-Hung Pan, Felix Sommer, Maren Falk-Paulsen, Thomas Ulas, Philipp Best, Antonella Fazio, Priyadarshini Kachroo, Anne Luzius, Marlene Jentzsch, Ateequr Rehman, Fabian Müller, Thomas Lengauer, Jörn Walter, Sven Künzel, John F. Baines, Stefan Schreiber…

New additions to the cancer precision medicine toolkit

New computational and database-driven tools are emerging to aid in the interpretation of cancer genomic data as its use becomes more common in clinical evidence-based cancer medicine. Two such open source tool...

Authors: Elaine R. Mardis

Integrated biology approach reveals molecular and pathological interactions among Alzheimer’s Aβ42, Tau, TREM2, and TYROBP in Drosophila models

Cerebral amyloidosis, neuroinflammation, and tauopathy are key features of Alzheimer’s disease (AD), but interactions among these features remain poorly understood. Our previous multiscale molecular network mo...

Authors: Michiko Sekiya, Minghui Wang, Naoki Fujisaki, Yasufumi Sakakibara, Xiuming Quan, Michelle E. Ehrlich, Philip L. De Jager, David A. Bennett, Eric E. Schadt, Sam Gandy, Kanae Ando, Bin Zhang and Koichi M. Iijima

Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations

While tumor genome sequencing has become widely available in clinical and research settings, the interpretation of tumor somatic variants remains an important bottleneck. Here we present the Cancer Genome Inte...

Authors: David Tamborero, Carlota Rubio-Perez, Jordi Deu-Pons, Michael P. Schroeder, Ana Vivancos, Ana Rovira, Ignasi Tusquets, Joan Albanell, Jordi Rodon, Josep Tabernero, Carmen de Torres, Rodrigo Dienstmann, Abel Gonzalez-Perez and Nuria Lopez-Bigas