Lean Big Data integration in systems biology and systems pharmacology.


:Data sets from recent large-scale projects can be integrated into one unified puzzle that can provide new insights into how drugs and genetic perturbations applied to human cells are linked to whole-organism phenotypes. Data that report how drugs affect the phenotype of human cell lines and how drugs induce changes in gene and protein expression in human cell lines can be combined with knowledge about human disease, side effects induced by drugs, and mouse phenotypes. Such data integration efforts can be achieved through the conversion of data from the various resources into single-node-type networks, gene-set libraries, or multipartite graphs. This approach can lead us to the identification of more relationships between genes, drugs, and phenotypes as well as benchmark computational and experimental methods. Overall, this lean 'Big Data' integration strategy will bring us closer toward the goal of realizing personalized medicine.


Trends Pharmacol Sci


Ma'ayan A,Rouillard AD,Clark NR,Wang Z,Duan Q,Kou Y




Has Abstract


2014-09-01 00:00:00














  • Pharmacological strategies in CNS trauma.

    abstract::Delayed biochemical changes play an important role in tissue damage resulting from traumatic injuries to the central nervous system. Identification of such 'secondary' injury factors has led to the development of various pharmacological strategies aimed at limiting this progressive tissue destruction. In this review, ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Faden AI,Salzman S

    更新日期:1992-01-01 00:00:00

  • Biological and clinical implications of the MTHFR C677T polymorphism.

    abstract::The enzyme methylenetetrahydrofolate reductase (MTHFR) directs folate species either to DNA synthesis or to homocysteine (Hcy) remethylation. The common MTHFR C677T polymorphism affects the activity of the enzyme and hence folate distribution. Under conditions of impaired folate status, the homozygous TT genotype has ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Ueland PM,Hustad S,Schneede J,Refsum H,Vollset SE

    更新日期:2001-04-01 00:00:00

  • Nicotine addiction: the possible role of functional upregulation.

    abstract::Upregulation of binding to nicotinic acetylcholine receptors (nAChRs) is observed in the brains of both smokers and animals chronically exposed to nicotine, although whether this in vivo change is accompanied by an increase in receptor function is unknown. In vitro recordings indicate that alpha4beta2- and alpha7-subt...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Buisson B,Bertrand D

    更新日期:2002-03-01 00:00:00

  • Size matters in activation/inhibition of ligand-gated ion channels.

    abstract::Cys loop, glutamate, and P2X receptors are ligand-gated ion channels (LGICs) with 5, 4, and 3 protomers, respectively. There is now growing atomic level understanding of their gating mechanisms. Although each family is unique in the architecture of the ligand-binding pocket, the pathway for motions to propagate from l...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Du J,Dong H,Zhou HX

    更新日期:2012-09-01 00:00:00

  • Deep Learning to Therapeutically Target Unreported Complexes.

    abstract::The disruption of large protein-protein (PP) interfaces remains a challenge in targeted therapy. Designing drugs that compete with binding partners is daunting, especially when the structure of the protein complex is unknown. To address the problem we propose a deep protein databank (PDB) learning platform to discover...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章


    authors: Fernández A

    更新日期:2019-08-01 00:00:00

  • Techniques: reporter mice - a new way to look at drug action.

    abstract::During the past decade remarkable progress in molecular genetics and the possibility of manipulating cells so that the expression of genes can directly 'report' on drug activity has produced major changes in drug development strategies. The recent description and pharmacological validation of reporter mice for in vivo...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Maggi A,Ottobrini L,Biserni A,Lucignani G,Ciana P

    更新日期:2004-06-01 00:00:00

  • Excitatory amino acid receptors, second messengers and regulation of intracellular Ca2+ in mammalian neurons.

    abstract::As we have learnt from earlier articles in our series on the pharmacology of excitatory amino acids, neurons and glia express several subtypes of excitatory amino acid receptor, the activation of which increases intracellular free calcium ion concentration. In this sixth article, Mark Mayer and Richard Miller detail t...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Mayer ML,Miller RJ

    更新日期:1990-06-01 00:00:00

  • Toxicology of simple and complex mixtures.

    abstract::Humans are exposed to mixtures of chemicals, rather than to individual chemicals. From a public health point of view, it is most relevant to answer the question of whether or not the components in a mixture interact in a way that results in an increase in their overall effect compared with the sum of the effects of th...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Groten JP,Feron VJ,Sühnel J

    更新日期:2001-06-01 00:00:00

  • Gene targeting--homing in on alpha 2-adrenoceptor-subtype function.

    abstract::The alpha-adrenoceptor was subdivided into three subtypes: alpha 2A-, alpha 2B- and alpha 2C-adrenoceptors almost ten years ago. Since then, the search has been on to discover and develop subtype-selective agonists and antagonists, but as yet no major breakthrough has been made. In the past year, several strains of ge...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: MacDonald E,Kobilka BK,Scheinin M

    更新日期:1997-06-01 00:00:00

  • An escort for GPCRs: implications for regulation of receptor density at the cell surface.

    abstract::G-protein-coupled receptors (GPCRs) are dynamically regulated by various mechanisms that tune their response to external stimuli. Modulation of their plasma membrane density, via trafficking between subcellular compartments, constitutes an important process in this context. Substantial information has been accumulated...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Achour L,Labbé-Jullié C,Scott MG,Marullo S

    更新日期:2008-10-01 00:00:00

  • The schizophrenic faces of PICK1.

    abstract::Schizophrenia is a grave psychiatric disorder with psychotic symptoms and an enigmatic etiology. Family studies have strongly indicated that genetic risk factors have a role in this disease. Recent findings, together with previously established evidence, highlight the PDZ-domain-containing protein interacting with C-k...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Dev KK,Henley JM

    更新日期:2006-11-01 00:00:00

  • What's all the FLAP about?: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases.

    abstract::Leukotrienes have physiological roles in innate immune responses and pathological roles in inflammatory diseases, such as asthma, allergic rhinitis and atherosclerosis. Anti-leukotriene therapy has proven benefits in the treatment of respiratory disease, either through the inhibition of leukotriene synthesis or the se...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Evans JF,Ferguson AD,Mosley RT,Hutchinson JH

    更新日期:2008-02-01 00:00:00

  • Endocannabinoid signaling at the periphery: 50 years after THC.

    abstract::In 1964, the psychoactive ingredient of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide) (AEA) in 1992 and 2-arachidonoylglycerol (2-AG) in 1995...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Maccarrone M,Bab I,Bíró T,Cabral GA,Dey SK,Di Marzo V,Konje JC,Kunos G,Mechoulam R,Pacher P,Sharkey KA,Zimmer A

    更新日期:2015-05-01 00:00:00

  • The troubled story of tachykinins and neurokinins.

    abstract::A family of peptides that shares a common C-terminal sequence (Phe-X-Gly-Leu-MetNH2) exists in mammalian and non-mammalian species. In mammals, three of these peptides (substance P, neurokinin A and neurokinin B) satisfy the criteria to be considered as neurotransmitters either in the central, peripheral or enteric ne...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章


    authors: Maggi CA

    更新日期:2000-05-01 00:00:00

  • Rho kinase: a target for treating urinary bladder dysfunction?

    abstract::Urinary incontinence and other urinary storage symptoms are frequent in the general population but available treatments have limited efficacy and tolerability. Rho kinase (ROCK) has a central role in the regulation of smooth muscle contraction, including that of the urinary bladder. Recent experimental evidence indica...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Peters SL,Schmidt M,Michel MC

    更新日期:2006-09-01 00:00:00

  • Does the pharmacology of oxycodone justify its increasing use as an analgesic?

    abstract::Oxycodone is a semisynthetic opioid analgesic that is increasingly used for the treatment of acute, cancer, and chronic non-malignant pain. Oxycodone was synthesized in 1917 but its pharmacological properties were not thoroughly studied until recently. Oxycodone is a fairly selective μ-opioid receptor agonist, but the...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Olkkola KT,Kontinen VK,Saari TI,Kalso EA

    更新日期:2013-04-01 00:00:00

  • Small molecule SIRT1 activators for the treatment of aging and age-related diseases.

    abstract::Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and ch...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Hubbard BP,Sinclair DA

    更新日期:2014-03-01 00:00:00

  • Diverse functions of muscarinic acetylcholine receptor subtypes.

    abstract::Muscarinic acetylcholine receptor subtypes m1, m3 and m5 couple strongly to phosphatidylinositol turnover and hence to intracellular Ca2+ concentration via pertussis toxin (PTX) sensitive and insensitive G proteins. The m2 and m4 muscarinic receptor subtypes strongly inhibit adenylyl cyclase production via PTX sensiti...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Lechleiter J,Peralta E,Clapham D

    更新日期:1989-12-01 00:00:00

  • In-vivo brain dialysis of neurotransmitters.

    abstract::Centrally acting drugs interfere with the function of central neurotransmitter systems. This often requires intact neuronal connections and is therefore best studied in vivo. Here, Gaetano Di Chiara describes the technique of brain dialysis, which permits direct in-vivo sampling of neurotransmitters and their metaboli...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Di Chiara G

    更新日期:1990-03-01 00:00:00

  • The developing use of heterozygous mutant mouse models in brain monoamine transporter research.

    abstract::5-Hydroxytryptamine (5-HT), dopamine and norepinephrine are important monoamine neurotransmitters implicated in multiple brain mechanisms and regulated by high-affinity transmembrane monoamine transporters. Although knockout mice lacking 5-HT, dopamine or norepinephrine transporters are widely used to assess brain mon...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Kalueff AV,Ren-Patterson RF,Murphy DL

    更新日期:2007-03-01 00:00:00

  • FAAH and anandamide: is 2-AG really the odd one out?

    abstract::Fatty acid amide hydrolase (FAAH) is a hydrolytic enzyme that recognizes as substrates and inactivates the two most studied endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG). Following the observation that endocannabinoids produced by tissues during pathological conditions often have protective roles, FAA...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章


    authors: Di Marzo V,Maccarrone M

    更新日期:2008-05-01 00:00:00

  • Pilot the pulse: controlling the multiplicity of receptor dynamics.

    abstract::G protein-coupled receptors (GPCRs) are involved in almost every (patho)physiological process, which explains their importance as drug targets. GPCRs have long been regarded as on/off-switches, which is reflected by direct activation or blockade of these receptors through the majority of marketed GPCR drugs. In recent...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章


    authors: Bock A,Kostenis E,Tränkle C,Lohse MJ,Mohr K

    更新日期:2014-12-01 00:00:00

  • A brief history of British Pharmacological Society meetings.

    abstract::The British Pharmacological Society (BPS) is currently celebrating its 75th anniversary. It is therefore a young society compared with some other biomedical societies and particularly when compared with the origins of the oldest learned societies. In this article, I briefly review the origins of learned societies and ...

    journal_title:Trends in pharmacological sciences

    pub_type: 历史文章,杂志文章


    authors: Green AR

    更新日期:2006-03-01 00:00:00

  • Adenosine A2B receptors: a novel therapeutic target in asthma?

    abstract::Adenosine is an endogenous nucleoside that modulates many physiological processes. Its actions are mediated by interaction with specific cell membrane receptors. Four subtypes of adenosine receptor have been cloned: A1, A2A, A2B and A3. Significant advancement has been made in our understanding of the molecular pharma...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Feoktistov I,Polosa R,Holgate ST,Biaggioni I

    更新日期:1998-04-01 00:00:00

  • Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells.

    abstract::Hypercontraction or abnormal contraction of vascular smooth muscle is a major cause of diseases such as hypertension and vasospasm of the coronary and cerebral arteries. A better understanding of the mechanism of regulation of smooth muscle contraction should lead to improved treatments for such diseases. Recent studi...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Fukata Y,Amano M,Kaibuchi K

    更新日期:2001-01-01 00:00:00

  • Stimulants and the developing brain.

    abstract::For almost 70 years, children have received stimulants for the treatment of attention deficit hyperactivity disorder [ADHD (initially called hyperkinetic syndrome)], with little understanding of the long-term effects of these drugs on brain development. The maturation and refinement of the brain during childhood and a...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Andersen SL

    更新日期:2005-05-01 00:00:00

  • Drugging unconventional targets: insights from Huntington's disease.

    abstract::Classical targeted drug discovery is based on targeting druggable targets, typically kinases and receptors of which the function can be agonized or antagonized. This strategy meets difficulties in cases such as Huntington's disease (HD) and similar neurodegenerative disorders, where the pathological function of the pr...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Yu S,Liang Y,Palacino J,Difiglia M,Lu B

    更新日期:2014-02-01 00:00:00

  • Muscarinic activation of potassium channels in cardiac myocytes: kinetic aspects of G protein function in vivo.

    abstract::Muscarinic agonists open potassium-selective K(ACh) channels in cardiac myocytes of pacemaker or atrial origin. Receptor activation is coupled to channel opening by a membrane bound guanine nucleotide-binding protein (GK) through a process that does not require cytoplasmic intermediates. We have used the muscarinic po...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Szabo G,Otero AS

    更新日期:1989-12-01 00:00:00

  • Tumour necrosis factor alpha and interleukin 1 signalling: do MAPKK kinases connect it all?

    abstract::The potent pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1) are capable of triggering biologically similar effects through activation of the same set of transcription factors. Based on recent findings it is now becoming evident that certain members of the mitogen-activated p...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Eder J

    更新日期:1997-09-01 00:00:00

  • Allosteric modulation of muscarinic acetylcholine receptors.

    abstract::Five subtypes of muscarinic acetylcholine receptors have been identified in mammalian tissues, but the selectivity of ligands that are active at these receptors is low. It is possible, however, that selective compounds may be developed by targeting their allosteric site(s). Important new insights into the mechanism of...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Tucek S,Proska J

    更新日期:1995-06-01 00:00:00