Visualizing patient journals by combining vital signs monitoring and natural language processing.

Conf Proc IEEE Eng Med Biol Soc. 2016 Aug;2016:2529-2532

Authors: Vilic A, Petersen JA, Hoppe K, Sorensen HB, Vilic A, Petersen JA, Hoppe K, Sorensen HB, Petersen JA, Vilic A, Hoppe K, Sorensen HB

Abstract
This paper presents a data-driven approach to graphically presenting text-based patient journals while still maintaining all textual information. The system first creates a timeline representation of a patients' physiological condition during an admission, which is assessed by electronically monitoring vital signs and then combining these into Early Warning Scores (EWS). Hereafter, techniques from Natural Language Processing (NLP) are applied on the existing patient journal to extract all entries. Finally, the two methods are combined into an interactive timeline featuring the ability to see drastic changes in the patients' health, and thereby enabling staff to see where in the journal critical events have taken place.

PMID: 28227035 [PubMed - in process]

S2NI: a mobile platform for nutrition monitoring from spoken data.

Conf Proc IEEE Eng Med Biol Soc. 2016 Aug;2016:1991-1994

Authors: Hezarjaribi N, Reynolds CA, Miller DT, Chaytor N, Ghasemzadeh H, Hezarjaribi N, Reynolds CA, Miller DT, Chaytor N, Ghasemzadeh H, Ghasemzadeh H, Reynolds CA, Chaytor N, Hezarjaribi N, Miller DT

Abstract
Diet and physical activity are important lifestyle and behavioral factors in self-management and prevention of many chronic diseases. Mobile sensors such as accelerometers have been used in the past to objectively measure physical activity or detect eating time. Diet monitoring, however, still relies on self-recorded data by end users where individuals use mobile devices for recording nutrition intake by either entering text or taking images. Such approaches have shown low adherence in technology adoption and achieve only moderate accuracy. In this paper, we propose development and validation of Speech-to-Nutrient-Information (S2NI), a comprehensive nutrition monitoring system that combines speech processing, natural language processing, and text mining in a unified platform to extract nutrient information such as calorie intake from spoken data. After converting the voice data to text, we identify food name and portion size information within the text. We then develop a tiered matching algorithm to search the food name in our nutrition database and to accurately compute calorie intake. Due to its pervasive nature and ease of use, S2NI enables users to report their diet routine more frequently and at anytime through their smartphone. We evaluate S2NI using real data collected with 10 participants. Our experimental results show that S2NI achieves 80.6% accuracy in computing calorie intake.

PMID: 28226908 [PubMed - in process]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"cystic fibrosis"

These pubmed results were generated on 2017/02/23

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Hidden Markov Models in Bioinformatics: SNV Inference from Next Generation Sequence.

Methods Mol Biol. 2017;1552:123-133

Authors: Bian J, Zhou X

Abstract
The rapid development of next generation sequencing (NGS) technology provides a novel avenue for genomic exploration and research. Hidden Markov models (HMMs) have wide applications in pattern recognition as well as Bioinformatics such as transcription factor binding sites and cis-regulatory modules detection. An application of HMM is introduced in this chapter with the in-deep developing of NGS. Single nucleotide variants (SNVs) inferred from NGS are expected to reveal gene mutations in cancer. However, NGS has lower sequence coverage and poor SNV detection capability in the regulatory regions of the genome. A specific HMM is developed for this purpose to infer the genotype for each position on the genome by incorporating the mapping quality of each read and the corresponding base quality on the reads into the emission probability of HMM. The procedure and the implementation of the algorithm is presented in detail for understanding and programming.

PMID: 28224495 [PubMed - in process]

Current Care and Investigational Therapies in Achondroplasia.

Curr Osteoporos Rep. 2017 Feb 21;:

Authors: Unger S, Bonafé L, Gouze E

Abstract
PURPOSE OF REVIEW: The goal of this review is to evaluate the management options for achondroplasia, the most common non-lethal skeletal dysplasia. This disease is characterized by short stature and a variety of complications, some of which can be quite severe.
RECENT FINDINGS: Despite several attempts to standardize care, there is still no widely accepted consensus. This is in part due to absence of concrete data on the incidence of sudden unexplained death in infants with achondroplasia and the best investigation for ascertaining which individuals could benefit from foramen magnum decompression surgery. In this review, we identify the different options of care and management for the various orthopedic, neurologic, and respiratory complications. In parallel, several innovative or drug repositioning therapies are being investigated that would restore bone growth but may also prevent complications. Achondroplasia is the most common non-lethal skeletal dysplasia. It is characterized by short stature and a variety of complications, some of which can be quite severe. Despite several attempts to standardize care, there is still no widely accepted consensus. This is in part due to absence of concrete data on the incidence of sudden unexplained death in infants with achondroplasia and the best investigation for ascertaining which individuals could benefit from foramen magnum decompression surgery. In this review, we identify the different options of care and management for the various orthopedic, neurologic, and respiratory complications. In parallel, several innovative or drug repositioning therapies are being investigated that would restore bone growth but may also prevent complications.

PMID: 28224446 [PubMed - as supplied by publisher]

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.

Lancet Oncol. 2017 Feb 17;:

Authors: Morris VK, Salem ME, Nimeiri H, Iqbal S, Singh P, Ciombor K, Polite B, Deming D, Chan E, Wade JL, Xiao L, Bekaii-Saab T, Vence L, Blando J, Mahvash A, Foo WC, Ohaji C, Pasia M, Bland G, Ohinata A, Rogers J, Mehdizadeh A, Banks K, Lanman R, Wolff RA, Streicher H, Allison J, Sharma P, Eng C

Abstract
BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA.
METHODS: We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169.
RESULTS: We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported.
INTERPRETATION: To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease.
FUNDING: National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor.

PMID: 28223062 [PubMed - as supplied by publisher]

Anal cancer: from an orphan disease to a curable malignancy?

Lancet Oncol. 2017 Feb 17;:

Authors: Cascinu S

PMID: 28223061 [PubMed - as supplied by publisher]

A rare case of rectal carcinoma and prostate carcinoma with coexistent Paget's disease mimicking bone metastases in both (18)F-FDG and (68)Ga PSMA PET/CT.

Eur J Nucl Med Mol Imaging. 2017 Jan;44(1):173

Authors: Sasikumar A, Joy A, Pillai MR, Raman V, Vasudevan A, Madhavan J

PMID: 27704192 [PubMed - indexed for MEDLINE]

An orphan disease: IgG4-related spinal pachymeningitis: report of 2 cases.

J Neurosurg Spine. 2016 Dec;25(6):790-794

Authors: Radotra BD, Aggarwal A, Kapoor A, Singla N, Chatterjee D

Abstract
IgG4-related disease is relatively new disease entity and a rare one, and our knowledge of this entity continues to evolve. It was first described in the pancreas and since then has been described in virtually every organ. Spinal involvement resulting in pachymeningitis is rare, and there are only 8 reported cases of the same to date, with the cervicothoracic spine being the most commonly affected region. The authors describe 2 cases in which the patients presented with spinal compression resulting in myeloradiculopathy (Case 1) and radiculopathy (Case 2). Imaging of spine in both cases revealed an ill-defined contrast-enhancing lesion at the lumbar level. Preoperatively, a diagnosis of spinal tumor was made, but intraoperatively no spinal tumor was found. The diagnosis was established histopathologically. The disease has no particular defining features clinically or radiologically and can mimic common spinal tumors. It is important to accurately diagnose this rare entity because of its multisystem involvement and progressive course. Strict treatment guidelines have yet to be formulated. Although histologically this disease can mimic other inflammatory conditions, the presence of storiform fibrosis and an increased number of IgG4-positive plasma cells can help in clarifying the diagnosis.

PMID: 27391401 [PubMed - indexed for MEDLINE]

Tashkeela: Novel corpus of Arabic vocalized texts, data for auto-diacritization systems.

Data Brief. 2017 Apr;11:147-151

Authors: Zerrouki T, Balla A

Abstract
Arabic diacritics are often missed in Arabic scripts. This feature is a handicap for new learner to read َArabic, text to speech conversion systems, reading and semantic analysis of Arabic texts. The automatic diacritization systems are the best solution to handle this issue. But such automation needs resources as diactritized texts to train and evaluate such systems. In this paper, we describe our corpus of Arabic diacritized texts. This corpus is called Tashkeela. It can be used as a linguistic resource tool for natural language processing such as automatic diacritics systems, dis-ambiguity mechanism, features and data extraction. The corpus is freely available, it contains 75 million of fully vocalized words mainly 97 books from classical and modern Arabic language. The corpus is collected from manually vocalized texts using web crawling process.

PMID: 28224131 [PubMed - in process]

Bottom-up and top-down computations in word- and face-selective cortex.

Elife. 2017 Feb 22;6:

Authors: Kay KN, Yeatman JD

Abstract
The ability to read a page of text or recognize a person's face depends on category-selective visual regions in ventral temporal cortex (VTC). To understand how these regions mediate word and face recognition, it is necessary to characterize how stimuli are represented and how this representation is used in the execution of a cognitive task. Here, we show that the response of a category-selective region in VTC can be computed as the degree to which the low-level properties of the stimulus match a category template. Moreover, we show that during execution of a task, the bottom-up representation is scaled by the intraparietal sulcus (IPS), and that the level of IPS engagement reflects the cognitive demands of the task. These results provide an account of neural processing in VTC in the form of a model that addresses both bottom-up and top-down effects and quantitatively predicts VTC responses.

PMID: 28226243 [PubMed - as supplied by publisher]

Cynomolgus macaques naturally infected with Trypanosoma cruzi-I exhibit an overall mixed pro-inflammatory/modulated cytokine signature characteristic of human Chagas disease.

PLoS Negl Trop Dis. 2017 Feb;11(2):e0005233

Authors: Vitelli-Avelar DM, Sathler-Avelar R, Mattoso-Barbosa AM, Gouin N, Perdigão-de-Oliveira M, Valério-Dos-Reis L, Costa RP, Elói-Santos SM, Gomes MS, Amaral LR, Teixeira-Carvalho A, Martins-Filho OA, Dick EJ, Hubbard GB, VandeBerg JF, VandeBerg JL

Abstract
BACKGROUND: Non-human primates have been shown to be useful models for Chagas disease. We previously reported that natural T. cruzi infection of cynomolgus macaques triggers clinical features and immunophenotypic changes of peripheral blood leukocytes resembling those observed in human Chagas disease. In the present study, we further characterize the cytokine-mediated microenvironment to provide supportive evidence of the utility of cynomolgus macaques as a model for drug development for human Chagas disease.
METHODS AND FINDINGS: In this cross-sectional study design, flow cytometry and systems biology approaches were used to characterize the ex vivo and in vitro T. cruzi-specific functional cytokine signature of circulating leukocytes from TcI-T. cruzi naturally infected cynomolgus macaques (CH). Results showed that CH presented an overall CD4+-derived IFN-γ pattern regulated by IL-10-derived from CD4+ T-cells and B-cells, contrasting with the baseline profile observed in non-infected hosts (NI). Homologous TcI-T. cruzi-antigen recall in vitro induced a broad pro-inflammatory cytokine response in CH, mediated by TNF from innate/adaptive cells, counterbalanced by monocyte/B-cell-derived IL-10. TcIV-antigen triggered a more selective cytokine signature mediated by NK and T-cell-derived IFN-γ with modest regulation by IL-10 from T-cells. While NI presented a cytokine network comprised of small number of neighborhood connections, CH displayed a complex cross-talk amongst network elements. Noteworthy, was the ability of TcI-antigen to drive a complex global pro-inflammatory network mediated by TNF and IFN-γ from NK-cells, CD4+ and CD8+ T-cells, regulated by IL-10+CD8+ T-cells, in contrast to the TcIV-antigens that trigger a modest network, with moderate connecting edges.
CONCLUSIONS: Altogether, our findings demonstrated that CH present a pro-inflammatory/regulatory cytokine signature similar to that observed in human Chagas disease. These data bring additional insights that further validate these non-human primates as experimental models for Chagas disease.

PMID: 28225764 [PubMed - in process]

IL-1β induced and p38(MAPK)-dependent activation of the mitogen-activated protein kinase (MAPK)-activated protein kinase (MK) 2 in hepatocytes: signal transduction with robust and concentration-independent signal amplification.

J Biol Chem. 2017 Feb 21;:

Authors: Kulawik A, Engesser R, Ehlting C, Raue A, Albrecht U, Hahn B, Lehmann WD, Gaestel M, Klingmüller U, Häussinger D, Timmer J, Bode JG

Abstract
The Interleukin (IL)-1β induced activation of the p38(MAPK)/MK2 pathway in hepatocytes is important for the control of acute phase response and regulation of liver regeneration. Many aspects of regulatory relevance of this pathway have been investigated in immune cells in the context of inflammation. However, very little is known about concentration-dependent activation kinetics and signal propagation in hepatocytes and the role of MK2. We established a mathematical model for IL-1β induced activation of the p38(MAPK)/MK2 pathway in hepatocytes that was calibrated to quantitative data on time- and IL-1β concentration-dependent phosphorylation of p38(MAPK) and MK2 in primary mouse hepatocytes. This analysis showed that in hepatocytes signal transduction from IL-1β via p38(MAPK) to MK2 is characterized by strong signal amplification. Quantification of p38(MAPK) and MK2 revealed that in hepatocytes at maximum 11.3 % of p38(MAPK) molecules and 36.5 % of MK2 molecules are activated in response to IL-1β. The mathematical model was experimentally validated employing phosphatase inhibitors and the p38(MAPK) inhibitor SB203580. Model simulations predicted an IC50 of 1 μM - 1.2 μM for SB203580 in hepatocytes. In silico analyses and experimental validation demonstrated that kinase activity of p38(MAPK) determines signal amplitude while phosphatase activity affects both signal amplitude and duration. p38(MAPK) and MK2 concentrations and responsiveness towards IL-1β was quantitatively compared between hepatocytes and macrophages. In macrophages the absolute p38(MAPK) and MK2 concentration was significantly higher. Finally, in line with experimental observations the mathematical model predicted a significantly higher EC50 for IL-1β induced pathway activation in macrophages compared to hepatoyces underscoring the importance of cell-type specific differences in pathway regulation.

PMID: 28223354 [PubMed - as supplied by publisher]

Biomechanical aspects of axonal damage in glaucoma: A brief review.

Exp Eye Res. 2017 Feb 18;:

Authors: Stowell C, Burgoyne C, Tamm ER, Ethier CR, Lasker/IRRF Initiative on Astrocytes and Glaucomatous Neurodegeneration Participants

Abstract
The biomechanical environment within the optic nerve head (ONH) is complex and is likely directly involved in the loss of retinal ganglion cells (RGCs) in glaucoma. Unfortunately, our understanding of this process is poor. Here we describe factors that influence ONH biomechanics, including ONH connective tissue microarchitecture and anatomy; intraocular pressure (IOP); and cerebrospinal fluid pressure (CSFp). We note that connective tissue factors can vary significantly from one individual to the next, as well as regionally within an eye, and that the understanding of ONH biomechanics is hindered by anatomical differences between small-animal models of glaucoma (rats and mice) and humans. Other challenges of using animal models of glaucoma to study the role of biomechanics include the complexity of assessing the degree of glaucomatous progression; and inadequate tools for monitoring and consistently elevating IOP in animal models. We conclude with a consideration of important open research questions/challenges in this area, including: (i) Creating a systems biology description of the ONH; (ii) addressing the role of astrocyte connective tissue remodeling and reactivity in glaucoma; (iii) providing a better characterization of ONH astrocytes and non-astrocytic constituent cells; (iv) better understanding the role of ONH astrocyte phagocytosis, proliferation and death; (v) collecting gene expression and phenotype data on a larger, more coordinated scale; and (vi) developing an implantable IOP sensor.

PMID: 28223180 [PubMed - as supplied by publisher]

compMS2Miner: an automatable metabolite identification, visualization and data-sharing R package for high-resolution LC-MS datasets.

Anal Chem. 2017 Feb 22;:

Authors: Edmands WM, Petrick LM, Barupal DK, Scalbert A, Wilson M, Wickliffe J, Rappaport SM

Abstract
A long-standing challenge of untargeted metabolomic profiling by ultrahigh performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) is efficient transition from unknown mass spectral features to confident metabolite annotations. The compMS2Miner (Comprehensive MS2 Miner) package was developed in the R language to facilitate rapid, comprehensive feature annotation using a peak-picker-output and MS2 data files as inputs. The number of MS2 spectra that can be collected during a metabolomic profiling experiment far outweigh the amount of time required for pain-staking manual interpretation, therefore a degree of software workflow autonomy is required for broad-scale metabolite annotation. CompMS2Miner integrates many useful tools in a single workflow for metabolite annotation and also a means to overview the MS2 data with a web application GUI compMS2Explorer (Comprehensive MS2 Explorer) that also facilitates data-sharing and transparency. The automatable compMS2Miner workflow consists of the following steps: i) matching unknown MS1 features to precursor MS2 scans, ii) filtration of spectral noise (dynamic noise filter), iii) generation of composite mass spectra by multiple similar spectrum signal summation and redundant/contaminant spectra removal iv) interpretation of possible fragment ion sub-structure using an internal database, v) annotation of unknowns with chemical and spectral databases with prediction of mammalian biotransformation metabolites, wrapper functions for in silico fragmentation software, nearest neighbor chemical similarity scoring, random forest based retention time prediction, text-mining based false positive removal/true positive ranking, chemical taxonomic prediction and differential evolution based global annotation score optimization and vi) network graph visualizations, data curation and sharing are made possible via the compMS2Explorer application. Metabolite identities and comments can also be recorded using an interactive table within compMS2Explorer. The utility of the package is illustrated with a dataset of blood serum samples from 7 diet induced obese (DIO) and 7 non-obese (NO) C57BL/6J mice, which were also treated with an antibiotic (streptomycin) to knockdown the gut microbiota. The results of fully autonomous and objective usage of compMS2Miner are presented here. All automatically annotated spectra output by the workflow are provided in the supporting information and can alternatively be explored as publically available compMS2Explorer applications for both positive and negative modes (https://wmbedmands.shinyapps.io/compMS2_mouseSera_POS&https://wmbedmands.shinyapps.io/compMS2_mouseSera_NEG). The workflow provided rapid annotation of a diversity of endogenous and gut microbially-derived metabolites affected by both diet and antibiotic treatment which conformed to previously published reports. Composite spectra (n=173) were autonomously matched to entries of the Massbank of North America (MoNA) spectral repository. These experimental and virtual (lipidBlast) spectra corresponded to 29 commonly endogenous compound classes (e.g. 51 lysophosphatidylcholines spectra) and were then used to calculate the ranking capability of 7 individual scoring metrics. It was found that an average of the 7 individual scoring metrics provided the most effective weighted average ranking ability of 3 for the MoNA matched spectra in spite of potential risk of false positive annotations emerging from automation. Minor structural differences such as relative carbon-carbon double bond positions were found in several cases to affect the correct rank of the MoNA annotated metabolite. The latest release and an example workflow is available in the package vignette (https://github.com/WMBEdmands/compMS2Miner) and a version of the published application is available on the shinyapps.io site (https://wmbedmands.shinyapps.io/compMS2Example).

PMID: 28225587 [PubMed - as supplied by publisher]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/02/22

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Integrating Pharmacoproteomics into Early-Phase Clinical Development: State-of-the-Art, Challenges, and Recommendations.

Int J Mol Sci. 2017 Feb 19;18(2):

Authors: Nandal S, Burt T

Abstract
Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating. We review the history, technologies, current usage, challenges, and potential for future use, and conclude with recommendations for integration of pharmacoproteomic in early-phase drug development.

PMID: 28218733 [PubMed - in process]

Novel plasma biomarker of atenolol-induced hyperglycemia identified through a metabolomics-genomics integrative approach.

Metabolomics (Los Angel). 2016 Aug;12:

Authors: de Oliveira FA, Shahin MH, Gong Y, McDonough CW, Beitelshees AL, Gums JG, Chapman AB, Boerwinkle E, Turner ST, Frye RF, Fiehn O, Kaddurah-Daouk R, Johnson JA, Cooper-DeHoff RM

Abstract
INTRODUCTION: While atenolol is an effective antihypertensive agent, its use is also associated with adverse events including hyperglycemia and incident diabetes that may offset the benefits of blood pressure lowering. By combining metabolomic and genomic data acquired from hypertensive individuals treated with atenolol, it may be possible to better understand the pathways that most impact the development of an adverse glycemic state.
OBJECTIVE: To identify biomarkers that can help predict susceptibility to blood glucose excursions during exposure to atenolol.
METHODS: Plasma samples acquired from 234 Caucasian participants treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses trial were analyzed by gas chromatography Time-Of-Flight Mass Spectroscopy. Metabolomics and genomics data were integrated by first correlating participant's metabolomic profiles to change in glucose after treatment with atenolol, and then incorporating genotype information from genes involved in metabolite pathways associated with glucose response.
RESULTS: Our findings indicate that the baseline level of β-alanine was associated with glucose change after treatment with atenolol (Q = 0.007, β = 2.97 mg/dL). Analysis of genomic data revealed that carriers of the G allele for SNP rs2669429 in gene DPYS, which codes for dihydropyrimidinase, an enzyme involved in β-alanine formation, had significantly higher glucose levels after treatment with atenolol when compared with non-carriers (Q = 0.05, β = 2.76 mg/dL). This finding was replicated in participants who received atenolol as an add-on therapy (P = 0.04, β = 1.86 mg/dL).
CONCLUSION: These results suggest that β-alanine and rs2669429 may be predictors of atenolol-induced hyperglycemia in Caucasian individuals and further investigation is warranted.

PMID: 28217400 [PubMed - in process]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"cystic fibrosis"

These pubmed results were generated on 2017/02/22

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Human enterovirus 71 protein interaction network prompts antiviral drug repositioning.

Sci Rep. 2017 Feb 21;7:43143

Authors: Han L, Li K, Jin C, Wang J, Li Q, Zhang Q, Cheng Q, Yang J, Bo X, Wang S

Abstract
As a predominant cause of human hand, foot, and mouth disease, enterovirus 71 (EV71) infection may lead to serious diseases and result in severe consequences that threaten public health and cause widespread panic. Although the systematic identification of physical interactions between viral proteins and host proteins provides initial information for the recognition of the cellular mechanism involved in viral infection and the development of new therapies, EV71-host protein interactions have not been explored. Here, we identified interactions between EV71 proteins and host cellular proteins and confirmed the functional relationships of EV71-interacting proteins (EIPs) with virus proliferation and infection by integrating a human protein interaction network and by functional annotation. We found that most EIPs had known interactions with other viruses. We also predicted ATP6V0C as a broad-spectrum essential host factor and validated its essentiality for EV71 infection in vitro. EIPs and their interacting proteins were more likely to be targets of anti-inflammatory and neurological drugs, indicating their potential to serve as host-oriented antiviral targets. Thus, we used a connectivity map to find drugs that inhibited EIP expression. We predicted tanespimycin as a candidate and demonstrated its antiviral efficiency in vitro. These findings provide the first systematic identification of EV71-host protein interactions, an analysis of EIP protein characteristics and a demonstration of their value in developing host-oriented antiviral therapies.

PMID: 28220872 [PubMed - in process]