Abstract:
:Here, we explore the potential of single-cell genomic analysis in blood for early detection of cancer; we consider a method that screens the presence of recurrent patterns of copy number (CN) alterations using sparse single-cell sequencing. We argue for feasibility, based on in silico analysis of existing single-cell data and cancer CN profiles. Sampling procedures from existing diploid single cells can render data for a cell with any given profile. Sampling from multiple published tumor profiles can interrogate cancer clonality via an algorithm that tests the multiplicity of close pairwise similarities among single-cell cancer genomes. The majority of common solid cancers would be detectable in this manner. As any early detection method must be verifiable and actionable, we describe how further analysis of suspect cells can aid in determining risk and anatomic origin. Future affordability rests on currently available procedures for tumor cell enrichment and inexpensive methods for single-cell analysis.
journal_name
Trends Mol Medjournal_title
Trends in molecular medicineauthors
Krasnitz A,Kendall J,Alexander J,Levy D,Wigler Mdoi
10.1016/j.molmed.2017.05.005subject
Has Abstractpub_date
2017-07-01 00:00:00pages
594-603issue
7eissn
1471-4914issn
1471-499Xpii
S1471-4914(17)30083-7journal_volume
23pub_type
杂志文章,评审abstract::Mechanisms underlying antipsychotic cardiometabolic adverse effects are incompletely understood. This hampers the identification of high-risk patients, low-risk antipsychotics and preventive/ameliorative treatments. Recent clinical, molecular and genetic data suggest that: (i) antipsychotic-naïve samples provide the g...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2010.10.010
更新日期:2011-02-01 00:00:00
abstract::When diabetes is diagnosed, the majority of insulin-secreting pancreatic β cells are already dysfunctional or destroyed. This β cell dysfunction/destruction usually takes place over many years, making timely detection and clinical intervention difficult. For this reason, there is immense interest in developing tools t...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2019.05.004
更新日期:2019-08-01 00:00:00
abstract::It is now widely accepted that the classic environmental risk factors for atherosclerosis only partly explain the incidence of coronary artery disease and the development of acute coronary syndromes. Therefore, genetic factors that vary among human populations seem to be involved in the clinical manifestations of such...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2008.08.004
更新日期:2008-10-01 00:00:00
abstract::Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The inflammatory and neurodegenerative pathways driving MS are modulated by DNA, lysine, and arginine methylation, as evidenced by studies made possible by novel tools for methylation detection or loss of function. We present evid...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2017.04.004
更新日期:2017-06-01 00:00:00
abstract::Over recent decades anti-angiogenic therapies (AATs) have produced promising results in the treatment of different malignancies. Unfortunately, resistance often develops and patients ultimately relapse. In an attempt to elucidate the causes of recurrence, most studies have focused on tumor responses to hypoxic conditi...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2017.01.002
更新日期:2017-03-01 00:00:00
abstract::Human natural killer (NK) and gamma delta (gammadelta) T cells are potent effectors involved in the destruction of abnormal cells. Accumulating clinical and experimental data point towards a key role for NK cells and gammadelta T cells in the control of most, if not all, haematological malignancies. This review focuse...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2009.04.005
更新日期:2009-06-01 00:00:00
abstract::Microglia are the resident macrophages of the central nervous system (CNS). They have important physiological functions in maintaining tissue homeostasis but also contribute to CNS pathology. Microglia respond to changes in the microenvironment, and the resulting reactive phenotype can be very diverse, with both neuro...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2018.11.005
更新日期:2019-02-01 00:00:00
abstract::Vascular calcification or ectopic mineralization in blood vessels is an active, cell-regulated process, increasingly recognized as a general cardiovascular risk factor. Remarkably, ectopic artery mineralization is frequently accompanied by decreased bone mineral density or disturbed bone turnover. This contradictory a...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2009.07.001
更新日期:2009-09-01 00:00:00
abstract::Targeting pathological tau protein in Alzheimer's disease (AD) and related tauopathies has shown great potential in animal models. Given that tau lesions correlate better with the degree of dementia than do amyloid-β (Aβ) plaques, their clearance may be clinically more efficacious than removing Aβ when cognitive defic...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2015.03.003
更新日期:2015-06-01 00:00:00
abstract::Innate immunity is the first line of defense against invading pathogens. A family of Toll-like receptors (TLRs) acts as primary sensors that detect a wide variety of microbial components and elicit innate immune responses. All TLR signaling pathways culminate in activation of the transcription factor nuclear factor-ka...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2007.09.002
更新日期:2007-11-01 00:00:00
abstract::T-cell-mediated autoimmunity participates in physiological defense, maintenance and repair of the adult brain. However, unless such autoimmune responses to insults are rigorously controlled, they might lead to an autoimmune disease or other immune-related defects, where destructive activity outweighs the beneficial ef...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2006.01.003
更新日期:2006-03-01 00:00:00
abstract::Rheumatoid arthritis (RA) is a multifactorial immune disease exhibiting diverse clinical responses to specific therapeutic agents. Such heterogeneity reflects variable activation of signaling pathways. Consequently, RA physiopathology has been linked to many immune cells and factors, with controversial observations fo...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2018.02.001
更新日期:2018-04-01 00:00:00
abstract::Induced pluripotent stem cells (iPSCs) are cutting edge biotechnology that may revolutionize medicine, and creating iPSCs from ethnically diverse individuals would generate valuable therapeutic and drug development tools. However, challenges must be overcome in creating the infrastructure and scientific capacity neede...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2012.10.005
更新日期:2012-12-01 00:00:00
abstract::Sphingosine kinase 1 (SphK1) knockout mice are protected against pulmonary hypertension and expression levels of the enzyme are increased in the lungs of pulmonary arterial hypertensive (PAH) patients. Moreover, sphingosine 1-phosphate can promote vascular remodeling/vasoconstriction in rodent and human pulmonary arte...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2017.07.001
更新日期:2017-09-01 00:00:00
abstract::There is much evidence suggesting that there is a strong relationship between the deterioration of brain lipid homeostasis, vascular changes and the pathogenesis of Alzheimer's disease (AD). These associations include: (1). recognition that a key cholesterol transporter, apolipoprotein E type 4, acts a major genetic r...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(03)00007-8
更新日期:2003-03-01 00:00:00
abstract::There is already considerable evidence from epidemiological, pathological and clinical reports that vascular factors are crucial in the pathogenesis of Alzheimer's disease (AD). Cerebral hypoperfusion has been shown to be a preclinical condition and a most accurate indicator for predicting whether people will develop ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.10.008
更新日期:2005-12-01 00:00:00
abstract::Recent reports on the impressive efficacy of adoptively transferred T cells to challenge cancer in early phase clinical trials have significantly raised the profile of T cell therapy. Concomitantly, general expectations are also raised by these reports, with the natural aspiration to deliver this therapy over a wide r...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2012.04.009
更新日期:2012-07-01 00:00:00
abstract::While the hippocampus has long been recognized as a brain structure specialized in mapping 'space' in rodents, human studies and now recent data from rodents have shown that its function extends well beyond spatial coding. Recently, an overlooked area of the hippocampus, CA2, has emerged as a critical region for socia...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2016.06.007
更新日期:2016-08-01 00:00:00
abstract::Medical diagnosis and phenotyping increasingly incorporate information from complex biological samples. This has promoted the development and clinical application of non-invasive metabolomics in exhaled air (breathomics). In respiratory medicine, expired volatile organic compounds (VOCs) are associated with inflammato...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2015.08.001
更新日期:2015-10-01 00:00:00
abstract::Non-alcoholic steatohepatitis (NASH), a cause of cirrhosis and hepatocellular carcinoma, is characterized by fatty infiltration of the liver, inflammation, hepatocellular damage and fibrosis. Progress has been made in understanding the molecular and cellular mechanisms implicated in the pathogenesis of this condition,...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2007.12.003
更新日期:2008-02-01 00:00:00
abstract::Ten percent of inherited diseases are caused by premature termination codon (PTC) mutations that lead to degradation of the mRNA template and to the production of a non-functional, truncated polypeptide. In addition, many acquired mutations in cancer introduce similar PTCs. In 1999, proof-of-concept for treating these...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2012.09.008
更新日期:2012-11-01 00:00:00
abstract::Alterations in histone lysine methylation and other epigenetic regulators of gene expression contribute to changes in brain transcriptomes in mood and psychosis spectrum disorders, including depression and schizophrenia. Genetic association studies and animal models implicate multiple lysine methyltransferases and dem...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2011.02.003
更新日期:2011-07-01 00:00:00
abstract::The social amoeba Dictyostelium discoideum is increasingly being used as a simple model for the investigation of problems that are relevant to human health. This article focuses on several recent examples of Dictyostelium-based biomedical research, including the analysis of immune-cell disease and chemotaxis, centroso...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2006.07.003
更新日期:2006-09-01 00:00:00
abstract::The programmed death 1 (PD-1) receptor and its ligands programmed death ligand 1 (PD-L1) and PD-L2, members of the CD28 and B7 families, play critical roles in T cell coinhibition and exhaustion. Overexpression of PD-L1 and PD-1 on tumor cells and tumor-infiltrating lymphocytes, respectively, correlates with poor dise...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2014.10.009
更新日期:2015-01-01 00:00:00
abstract::In the coming years, molecular diagnostics will continue to be of critical importance to public health worldwide. It will facilitate the detection and characterization of disease, as well as monitoring of the drug response, and will assist in the identification of genetic modifiers and disease susceptibility. A wide r...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/s1471-4914(02)02331-6
更新日期:2002-06-01 00:00:00
abstract::Many infectious agents elicit a type I interferon response but, until recently, the molecular details that coordinate interferon (IFN)-alpha and -beta expression during infection were unknown. Innate immune pattern recognition receptors, including Toll-like receptors and cytoplasmic RNA helicases such as retinoic acid...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.07.006
更新日期:2005-09-01 00:00:00
abstract::Theoretical, desirable features of second-generation metal-on-metal (MoM) hip prostheses have led to their widespread use. However, the bearing surfaces, consisting of complex cobalt-chromium alloys, are subject to wear and the release of cobalt and chromium (CoCr) nanoparticles. These nanoparticles can reduce cellula...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2011.12.002
更新日期:2012-03-01 00:00:00
abstract::The vanilloid receptor TRPV1 is now recognized as a molecular integrator of painful stimuli ranging from noxious heat to endovanilloids in inflammation. Pharmacological blockade of TRPV1 represents a new strategy in pain relief. TRPV1 antagonists are expected to prevent pain by silencing receptors where pain is genera...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2006.09.001
更新日期:2006-11-01 00:00:00
abstract::The systemic inflammatory response is biologically complex, redundant, and activated by both infectious and noninfectious triggers. Its manipulation can cause both benefit and harm. More than 100 randomized clinical trials have tested the hypothesis that modulating the septic response to infection can improve survival...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2014.01.007
更新日期:2014-04-01 00:00:00
abstract::Defects in the regulation of apoptosis (programmed cell death) contribute to many diseases, including pathologies associated with cell loss (e.g. stroke, heart failure, neurodegeneration and AIDS), and disorders characterized by a failure to eliminate harmful cells (e.g. cancer, autoimmunity). Apoptosis is caused by a...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(01)02026-3
更新日期:2001-07-01 00:00:00