Commentaries

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

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

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

The emerging roles of exosomes in the modulation of immune responses in cancer

Exosomes are promising tools for improving cancer care, but conversely may also contribute to tumor progression. Here, we highlight recently discovered roles of exosomes in modulating immune responses in cance...

Authors: Paul Kurywchak, Jena Tavormina and Raghu Kalluri

Detection of Creutzfeldt-Jakob disease prions in skin: implications for healthcare

Evidence has recently been reported of prion seeding activity in skin tissue from patients with sporadic Creutzfeldt-Jakob disease (sCJD). This is relevant information for infection control measures during sur...

Authors: Akin Nihat and Simon Mead

Advances in liquid biopsy approaches for early detection and monitoring of cancer

Progress in sensitive analytical approaches has opened new avenues for the detection of cells or products such as circulating cell-free DNA released by tumors. These ‘liquid biopsies’ are being explored in cli...

Authors: Anna Babayan and Klaus Pantel

The microbiome in precision medicine: the way forward

Novel associations between the human microbiome and health and disease are routinely emerging, and important host–microbiome interactions are targets for new diagnostics and therapeutics. Understanding how bro...

Authors: Joseph F. Petrosino

Endophenotypes in psychiatric disease: prospects and challenges

Endophenotypes, quantitative neurobehavioral traits that index genetic susceptibility for a psychiatric disorder, have been examined in thousands of studies. Nevertheless, they have underexploited potential to...

Authors: William G. Iacono

Calcitonin gene-related peptide (receptor) antibodies: an exciting avenue for migraine treatment

Specific prophylactic migraine treatments are urgently needed because of the unmet needs of many migraine patients. Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have recently sho...

Authors: Antoinette MaassenVanDenBrink, Gisela M. Terwindt and Arn M. J. M. van den Maagdenberg

Synaptic dysfunction in complex psychiatric disorders: from genetics to mechanisms

Breakthroughs on many fronts have provided strong evidence to support synaptic dysfunction as a causal factor for neuropsychiatric diseases. Genetic studies have identified variants implicated in novel biologi...

Authors: Xinyuan Wang, Kimberly M. Christian, Hongjun Song and Guo-li Ming

Modeling psychiatric disorders using patient stem cell-derived neurons: a way forward

Our understanding of the neurobiology of psychiatric disorders remains limited, and biomarker-based clinical management is yet to be developed. Induced pluripotent stem cell (iPSC) technology has revolutionize...

Authors: Krishna C. Vadodaria, Debha N. Amatya, Maria C. Marchetto and Fred H. Gage

Mapping genetic variations to three-dimensional protein structures to enhance variant interpretation: a proposed framework

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are pred...

Authors: Gustavo Glusman, Peter W. Rose, Andreas Prlić, Jennifer Dougherty, José M. Duarte, Andrew S. Hoffman, Geoffrey J. Barton, Emøke Bendixen, Timothy Bergquist, Christian Bock, Elizabeth Brunk, Marija Buljan, Stephen K. Burley, Binghuang Cai, Hannah Carter, JianJiong Gao…

Narrowing the spectrum: the new frontier of precision antimicrobials

Antibiotics have become the standard of care for bacterial infections. However, rising rates of antibiotic-resistant infections are outpacing the development of new antimicrobials. Broad-spectrum antibiotics a...

Authors: Alexandra E. Paharik, Henry L. Schreiber IV, Caitlin N. Spaulding, Karen W. Dodson and Scott J. Hultgren

Emerging mechanisms and novel targets in allergic inflammation and asthma

Airway inflammation is key to the severity and persistence of asthma. Recent studies have revealed novel immune mechanisms that target dendritic cells, T helper 2 cytokines, regulatory T cells, and type 2 inna...

Authors: Scott T. Weiss

Prospects for using risk scores in polygenic medicine

Genome-wide association studies have made strides in identifying common variation associated with disease. The modest effect sizes preclude risk prediction based on single genetic variants, but polygenic risk ...

Authors: Cathryn M. Lewis and Evangelos Vassos

Key challenges in bringing CRISPR-mediated somatic cell therapy into the clinic

Genome editing using clustered regularly interspersed short palindromic repeats (CRISPR) and CRISPR-associated proteins offers the potential to facilitate safe and effective treatment of genetic diseases refra...

Authors: Dianne Nicol, Lisa Eckstein, Michael Morrison, Jacob S. Sherkow, Margaret Otlowski, Tess Whitton, Tania Bubela, Kathryn P. Burdon, Don Chalmers, Sarah Chan, Jac Charlesworth, Christine Critchley, Merlin Crossley, Sheryl de Lacey, Joanne L. Dickinson, Alex W. Hewitt…

Genetic and epigenetic studies of adiposity and cardiometabolic disease

Over 300 million adults are obese, but little is known about the impact of obesity on cardiovascular health. We discuss recent genetic and epigenetic studies of adiposity that indicate a causal role for genera...

Authors: Michael V. Holmes, Sara L. Pulit and Cecilia M. Lindgren

Bugs, drugs, and HIV: the role of the vaginal microbiome in HIV risk and antiretroviral efficacy for HIV prevention

Advances in molecular tools to characterize the microbiome have led to the discovery of unique roles for microbes in human disease. Findings that the female genital microbiome can influence HIV acquisition and...

Authors: Lenine J. P. Liebenberg, Derseree Archary, Aida Sivro and Douglas S. Kwon

Host gene–microbiome interactions: molecular mechanisms in inflammatory bowel disease

Recent studies have identified links between host genetic variants and microbial recognition of the microbiome. Defects in host–microbiome interactions in individuals harboring inflammatory bowel disease risk ...

Authors: Hiutung Chu

Defining the role of Lgr5⁺ stem cells in colorectal cancer: from basic research to clinical applications

Intestinal epithelium is structured by two distinct components: the villi and the crypts. The crypts harbor stem cells expressing Lgr5 and thus have been a representative model to study tissue stem cell functi...

Authors: Masayuki Fujii and Toshiro Sato

Computing patient data in the cloud: practical and legal considerations for genetics and genomics research in Europe and internationally

Biomedical research is becoming increasingly large-scale and international. Cloud computing enables the comprehensive integration of genomic and clinical data, and the global sharing and collaborative processi...

Authors: Fruzsina Molnár-Gábor, Rupert Lueck, Sergei Yakneen and Jan O. Korbel

Dissecting the human microbiome with single-cell genomics

Recent advances in genome sequencing of single microbial cells enable the assignment of functional roles to members of the human microbiome that cannot currently be cultured. This approach can reveal the genom...

Authors: Andrew C. Tolonen and Ramnik J. Xavier

Novel insights into the HLA class I immunopeptidome and T-cell immunosurveillance

Advances in mass spectrometry have allowed the high-throughput quantitative identification of human leukocyte antigen (HLA) class I ligands, and recent studies have reported on the breadth and diversity of the...

Authors: Cornelis J. M. Melief and Jan H. Kessler

Pancreatic β-cell regeneration: advances in understanding the genes and signaling pathways involved

Recent advances in β-cell regeneration in vivo are providing insights into the mechanisms involved in the conversion of distinct pancreatic cell lineages into β cells. These mechanisms mostly involve reactivat...

Authors: Solomon Afelik and Meritxell Rovira

Schizophrenia and substance use comorbidity: a genome-wide perspective

Dual diagnosis with substance use disorders (SUDs) consistently contributes to the premature mortality and increased disability observed in schizophrenia. Large genome-wide association studies are providing th...

Authors: Renato Polimanti, Arpana Agrawal and Joel Gelernter

Schizophrenia and the dynamic genome

Authors: Patrick F. Sullivan

MeCP2 mutations: progress towards understanding and treating Rett syndrome

Rett syndrome is a profound neurological disorder caused by mutations in the MECP2 gene, but preclinical research has indicated that it is potentially treatable. Progress towards this goal depends on the developm...

Authors: Ruth R. Shah and Adrian P. Bird

Emerging links between m⁶A and misregulated mRNA methylation in cancer

N ⁶-methyladenosine (m⁶A) in mRNA has emerged as a crucial epitranscriptomic modification that controls cellular differentiation and pluripotency. Recent studies a...

Authors: Samie R. Jaffrey and Michael G. Kharas

Reconciling evidence-based medicine and precision medicine in the era of big data: challenges and opportunities

This era of groundbreaking scientific developments in high-resolution, high-throughput technologies is allowing the cost-effective collection and analysis of huge, disparate datasets on individual health. Prop...

Authors: Jacques S. Beckmann and Daniel Lew

Mitochondrial replacement approaches: challenges for clinical implementation

The advent of mitochondrial replacement techniques poses many scientific, regulatory, and ethical questions. Previous studies suggest good safety and efficacy profiles of these techniques, but challenges remai...

Authors: Thomas Klopstock, Barbara Klopstock and Holger Prokisch

Looking beyond the cancer cell for effective drug combinations

Combinations of therapies are being actively pursued to expand therapeutic options and deal with cancer’s pervasive resistance to treatment. Research efforts to discover effective combination treatments have f...

Authors: Jonathan R. Dry, Mi Yang and Julio Saez-Rodriguez

Genome editing: progress and challenges for medical applications

The development of the CRISPR-Cas platform for genome editing has greatly simplified the process of making targeted genetic modifications. Applications of genome editing are expected to have a substantial impa...

Authors: Dana Carroll

Acquired resistance to anti-PD1 therapy: checkmate to checkpoint blockade?

Anti-programmed cell death 1 (PD1) immunotherapies are among the most effective anti-cancer immunotherapies available; however, a large number of patients present with or develop resistance to them. Unfortunat...

Authors: Jake S. O’Donnell, Mark J. Smyth and Michele W. L. Teng

Integrating precision cancer medicine into healthcare—policy, practice, and research challenges

Precision medicine (PM) can be defined as a predictive, preventive, personalized, and participatory healthcare service delivery model. Recent developments in molecular biology and information technology make P...

Authors: Gabrielle Bertier, Jian Carrot-Zhang, Vassilis Ragoussis and Yann Joly

Germline, hematopoietic, mosaic, and somatic variation: interplay between inherited and acquired genetic alterations in disease assessment

Advances in genetic analysis have revealed new complexities in the interpretation of genetic variants. Correct assessment of a genetic variant relies on the clinical context and knowledge of the underlying bio...

Authors: Eric Q. Konnick and Colin C. Pritchard

Mobile real-time surveillance of Zika virus in Brazil

The World Health Organization has declared Zika virus an international public health emergency. Knowledge of Zika virus genomic epidemiology is currently limited due to challenges in obtaining and processing s...

Authors: Nuno Rodrigues Faria, Ester C. Sabino, Marcio R. T. Nunes, Luiz Carlos Junior Alcantara, Nicholas J. Loman and Oliver G. Pybus

Genetic and epigenetic analysis of schizophrenia in blood—a no-brainer?

Several recent studies have investigated either genetic or epigenetic variation in schizophrenia. A recent study presents comprehensive analyses of blood samples to better characterize the combined role of gen...

Authors: Andrew E. Jaffe and Joel E. Kleinman

A missing link in the bench-to-bedside paradigm: engaging regulatory stakeholders in clinical genomics research

For genomic medicine research to be fully translated into clinical care, it is critical for researchers to engage stakeholders who ultimately regulate the use of genomic technologies and therapeutics within he...

Authors: Julianne M. O’Daniel and Jonathan S. Berg

Migraine genetics: from genome-wide association studies to translational insights

Authors: Padhraig Gormley, Bendik S. Winsvold, Dale R. Nyholt, Mikko Kallela, Daniel I. Chasman and Aarno Palotie

Genetic pleiotropy in complex traits and diseases: implications for genomic medicine

Authors: Jacob Gratten and Peter M. Visscher

Making sense of big data in health research: Towards an EU action plan

Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation comb...

Authors: Charles Auffray, Rudi Balling, Inês Barroso, László Bencze, Mikael Benson, Jay Bergeron, Enrique Bernal-Delgado, Niklas Blomberg, Christoph Bock, Ana Conesa, Susanna Del Signore, Christophe Delogne, Peter Devilee, Alberto Di Meglio, Marinus Eijkemans, Paul Flicek…

Taming the genome: towards better genetic test interpretation

Advances in sequencing technology have taught us much about the human genome, including how difficult it is to interpret rare variation. Improvements in genetic test interpretation are likely to come through d...

Authors: Colleen Caleshu and Euan A. Ashley

Environment-driven somatic mosaicism in brain disorders

The identification of somatic mosaicism in the brain lends a new perspective to our understanding of the role of gene and environment interactions in psychiatric disease risk. Somatic mutations, such as retrot...

Authors: Tracy A. Bedrosian, Sara Linker and Fred H. Gage

Strain-level dissection of the contribution of the gut microbiome to human metabolic disease

The gut microbiota has been linked with metabolic diseases in humans, but demonstration of causality remains a challenge. The gut microbiota, as a complex microbial ecosystem, consists of hundreds of individua...

Authors: Chenhong Zhang and Liping Zhao

Mood by microbe: towards clinical translation

There is a growing realization that the gut–brain axis plays a key role in maintaining brain health and the stress response. Recently, the gut microbiota has emerged as a master regulator of this axis. Thus, o...

Authors: Timothy G. Dinan and John F. Cryan

Translating the vaginal microbiome: gaps and challenges

Management, manipulation, and restoration of a robust vaginal microbiota has the potential to vastly improve women’s health and disease prevention. However, a systems level understanding of how the vaginal mic...

Authors: Jacques Ravel and Rebecca M. Brotman

The virome: a missing component of biological interaction networks in health and disease

Host-associated viral populations, viromes, have been understudied relative to their contribution to human physiology. Viruses interact with host gene networks, influencing both health and disease. Analysis of...

Authors: Scott A. Handley

Exploring the implications of distinct mutational signatures and mutation rates in aging and cancer

Signatures of mutagenesis provide a powerful tool for dissecting the role of somatic mutations in both normal and pathological processes. Significantly, cancer genomes are dominated by mutation signatures dist...

Authors: Edward J. Fox, Jesse J. Salk and Lawrence A. Loeb

The miR-143/miR-145 cluster and the tumor microenvironment: unexpected roles

miR-143 and miR-145 have been widely described as tumor suppressors. Recent findings suggest these microRNAs (miRNAs) have a critical role that affects the stroma rather than epithelial cells. Understanding th...

Authors: Maria Inês Almeida and George Adrian Calin

Molecular subtyping and improved treatment of neurodevelopmental disease

The next-generation sequencing revolution has substantially increased our understanding of the mutated genes that underlie complex neurodevelopmental disease. Exome sequencing has enabled us to estimate the nu...

Authors: Holly A. F. Stessman, Tychele N. Turner and Evan E. Eichler