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Biomarker discovery

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https://www.readbyqxmd.com/read/28214264/identification-of-candidate-cerebrospinal-fluid-biomarkers-in-parkinsonism-using-quantitative-proteomics
#1
N K Magdalinou, A J Noyce, R Pinto, E Lindstrom, J Holmén-Larsson, M Holtta, K Blennow, H R Morris, T Skillbäck, T T Warner, A J Lees, I Pike, M Ward, H Zetterberg, J Gobom
INTRODUCTION: Neurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than α-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive. OBJECTIVES: To study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls...
January 31, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28212429/the-p53-isoform-delta133p53%C3%A3-regulates-cancer-cell-apoptosis-in-a-rhob-dependent-manner
#2
Nikola Arsic, Alexandre Ho-Pun-Cheung, Crapez Evelyne, Eric Assenat, Marta Jarlier, Christelle Anguille, Manon Colard, Mikaël Pezet, Pierre Roux, Gilles Gadea
The TP53 gene plays essential roles in cancer. Conventionally, wild type (WT) p53 is thought to prevent cancer development and metastasis formation, while mutant p53 has transforming abilities. However, clinical studies failed to establish p53 mutation status as an unequivocal predictive or prognostic factor of cancer progression. The recent discovery of p53 isoforms that can differentially regulate cell cycle arrest and apoptosis suggests that their expression, rather than p53 mutations, could be a more clinically relevant biomarker in patients with cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28210711/intergenically-spliced-chimeric-rnas-in-cancer
#3
Yuemeng Jia, Zhongqiu Xie, Hui Li
Gene fusions and their encoded products (fusion RNAs and proteins) are viewed as one of the hallmarks of cancer. Traditionally, they were thought to be generated solely by chromosomal rearrangements. However, recent discoveries of trans-splicing and cis-splicing events between neighboring genes, suggest that there are other mechanisms to generate chimeric fusion RNAs without corresponding changes in DNA. In addition, chimeric RNAs have been detected in normal physiology, complicating the use of fusions in cancer detection and therapy...
September 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28208771/detecting-blood-based-biomarkers-in-metastatic-breast-cancer-a-systematic-review-of-their-current-status-and-clinical-utility
#4
REVIEW
A M Sofie Berghuis, Hendrik Koffijberg, Jai Prakash, Leon W M M Terstappen, Maarten J IJzerman
Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the available evidence of known blood-based biomarkers in metastatic breast cancer, regarding their clinical utility and state-of-the-art position in the validation process. The initial search yielded 1078 original studies, of which 420 were assessed for eligibility...
February 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207922/mass-spectrometry-for-the-discovery-of-biomarkers-of-sepsis
#5
REVIEW
Katelyn R Ludwig, Amanda B Hummon
Sepsis is a serious medical condition that occurs in 30% of patients in intensive care units (ICUs). Early detection of sepsis is key to prevent its progression to severe sepsis and septic shock, which can cause organ failure and death. Diagnostic criteria for sepsis are nonspecific and hinder a timely diagnosis in patients. Therefore, there is currently a large effort to detect biomarkers that can aid physicians in the diagnosis and prognosis of sepsis. Mass spectrometry is often the method of choice to detect metabolomic and proteomic changes that occur during sepsis progression...
February 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28202367/exosomes-therapy-delivery-tools-and-biomarkers-of-diseases
#6
REVIEW
Lucio Barile, Giuseppe Vassalli
Virtually all cells in the organism secrete extracellular vesicles (EVs), a heterogeneous population of lipid bilayer membrane-enclosed vesicles that transport and deliver payloads of proteins and nucleic acids to recipient cells, thus playing central roles in cell-cell communications. Exosomes, nanosized EVs of endosomal origin, regulate many pathophysiological processes including immune responses and inflammation, tumour growth, and infection. Healthy subjects and patients with different diseases release exosomes with different RNA and protein contents into the circulation, which can be measured as biomarkers...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28198667/pan-cancer-analysis-of-frequent-dna-co-methylation-patterns-reveals-consistent-epigenetic-landscape-changes-in-multiple-cancers
#7
Jie Zhang, Kun Huang
BACKGROUND: DNA methylation is the major form of epigenetic modifications through which the cell regulates the gene expression and silencing. There have been extensive studies on the roles of DNA methylation in cancers, and several cancer drugs were developed targeting this process. However, DNA co-methylation cluster has not been examined in depth, and co-methylation in multiple cancer types has never been studied previously. RESULTS: In this study, we applied newly developed lmQCM algorithm to mine co-methylation clusters using methylome data from 11 cancer types in TCGA database, and found frequent co-methylated gene clusters exist in these cancer types...
January 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28198377/nmr-metabolic-fingerprints-of-murine-melanocyte-and-melanoma-cell-lines-application-to-biomarker-discovery
#8
Arquimedes Paixão de Santana-Filho, Thiago Jacomasso, Daniel Suss Riter, Andersson Barison, Marcello Iacomini, Sheila Maria Brochado Winnischofer, Guilherme Lanzi Sassaki
Melanoma is the most aggressive type of skin cancer and efforts to improve the diagnosis of this neoplasia are largely based on the use of cell lines. Metabolomics is currently undergoing great advancements towards its use to screening for disease biomarkers. Although NMR metabolomics includes both 1D and 2D methodologies, there is a lack of data in the literature regarding heteronuclear 2D NMR assignments of the metabolome from eukaryotic cell lines. The present study applied NMR-based metabolomics strategies to characterize aqueous and lipid extracts from murine melanocytes and melanoma cell lines with distinct tumorigenic potential, successfully obtaining fingerprints of the metabolites from the extracts of the cell lines by means of 2D NMR HSQC correlation maps...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198151/comparative-proteomic-analysis-of-the-influence-of-gender-and-acid-stimulation-on-normal-human-saliva-using-lc-ms-ms
#9
Xiaoping Xiao, Yaoran Liu, Zhengguang Guo, Xiaoyan Liu, Haidan Sun, Qian Li, Wei Sun
Human saliva is an important source for disease biomarker discovery. In this work, we investigate the influence of gender and acid stimulation on the normal human salivary proteome. Un-stimulated and acid-stimulated saliva samples from 5 males and 5 females were labeled with 4-plex iTRAQ and analyzed by 2-DLC MS/MS. A total of 1,770 proteins were identified, and 82 proteins in un-stimulated saliva were found to be gender-specific. These proteins were mainly associated with immune function, metabolism and inflammation...
February 15, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28197537/fusion-rna-profiling-provides-hints-on-cell-of-origin-of-mysterious-tumor
#10
Zhongqiu Xie, Hui Li
Biological samples can be grouped into separate clusters based on their gene expression profiles. This approach has yielded meaningful biological insights and facilitated biomarker discoveries. Recently, we developed another approach to study connections between biological samples based on their fusion RNA expression. We have used this approach to provide insights into the cell of origin for a mysterious tumor, alveolar rhabdomyosarcoma.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28193625/deep-sequencing-of-urinary-rnas-for-bladder-cancer-molecular-diagnostics
#11
Mandy L Y Sin, Kathleen E Mach, Rahul Sinha, Fan Wu, Dharati Trivedi, Emanuela Altobelli, Kristin C Jensen, Debashis Sahoo, Ying Lu, Joseph C Liao
PURPOSE: The majority of bladder cancer patients present with localized disease and are managed by transurethral resection. However, the high rate of recurrence necessitates lifetime cystoscopic surveillance. Developing a sensitive and specific urine-based test would significantly improve bladder cancer screening, detection, and surveillance. EXPERIMENTAL DESIGN: RNA-seq was used for biomarker discovery to directly assess the gene expression profile of exfoliated urothelial cells in urine derived from bladder cancer patients (n=13) and controls (n=10)...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28192239/super-silac-mix-coupled-with-sim-aims-assays-for-targeted-verification-of-phosphopeptides-discovered-in-a-large-scale-phosphoproteome-analysis-of-hepatocellular-carcinoma
#12
Yu-Tsun Lin, Kun-Yi Chien, Chia-Chun Wu, Wen-Yu Chang, Lichieh Julie Chu, Min-Chi Chen, Chau-Ting Yeh, Jau-Song Yu
: Plentiful studies have established a close association between aberrant phosphorylation and hepatocellular carcinoma (HCC). Here, we applied a quantitative phosphoproteomics platform combining dimethylation labeling and online 3D strong cation exchange chromatography (SCX)-titanium oxide (TiO2)/RP-LTQ-Orbitrap to compare phosphoproteomes between three pairs of HCC tissues and non-tumor counterparts. This analysis yielded 7868 quantifiable phosphopeptides and numerous up- or down-regulated candidates...
February 9, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28191944/discovery-of-cell-type-specific-and-disease-related-enzymatic-activity-changes-via-global-evaluation-of-peptide-metabolism
#13
Jun Onagi, Toru Komatsu, Yuki Ichihashi, Yugo Kuriki, Mako Kamiya, Takuya Terai, Tasuku Ueno, Kenjiro Hanaoka, Hiroyuki Matsuzaki, Keisuke Hata, Toshiaki Watanabe, Tetsuo Nagano, Yasuteru Urano
Cellular homeostasis is maintained by a complex network of reactions catalyzed by enormous numbers of enzymatic activities (the enzymome), which serve to determine the phenotypes of cells. Here, we focused on the enzymomics of proteases and peptidases, because these enzymes are an important class of disease-related proteins. We describe a system that (A) simultaneously evaluates metabolic activities of peptides using series of exogenous peptide substrates and (B) identifies the enzymes that metabolize the specified peptide substrate with high throughput...
February 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28190990/the-translation-of-lipid-profiles-to-nutritional-biomarkers-in-the-study-of-infant-metabolism
#14
Animesh Acharjee, Philippa Prentice, Carlo Acerini, James Smith, Ieuan A Hughes, Ken Ong, Julian L Griffin, David Dunger, Albert Koulman
INTRODUCTION: Links between early life exposures and later health outcomes may, in part, be due to nutritional programming in infancy. This hypothesis is supported by observed long-term benefits associated with breastfeeding, such as better cognitive development in childhood, and lower risks of obesity and high blood pressure in later life. However, the possible underlying mechanisms are expected to be complex and may be difficult to disentangle due to the lack of understanding of the metabolic processes that differentiate breastfed infants compared to those receiving just formula feed...
2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28188804/metabolite-profiling-of-infection-associated-metabolic-markers-of-onchocerciasis
#15
Sasisekhar Bennuru, Sara Lustigman, David Abraham, Thomas B Nutman
The global efforts for onchocerciasis elimination may require additional tools (safe micro and macrofilaricidal drugs, vaccines and biomarkers) as elimination efforts move toward the "end game". Efforts toward the identification of suitable biomarkers have focused on specific protein(s) and/or nucleic acids, but metabolites present an alternative option as they have limited half-lives and are the result of combinatorial effects. In comparison to previously used methodology of LC-MS for metabolomic approaches, we used a non-targeted capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) to analyze the serum metabolic profiles of Ov-infected and -uninfected individuals (n=20)...
February 7, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28188532/pathway-informed-discovery-and-targeted-proteomic-workflows-using-mass-spectrometry
#16
Caroline S Chu, Christine A Miller, Andy Gieschen, Steve M Fischer
Recent advancements in mass spectrometry (MS) and data analysis software have enabled new strategies for biological discovery using proteomics. Proteomics has evolved from routine discovery and identification of proteins to integrated multi-omics projects relating specific proteins to their genes and metabolites. Using additional information, such as that contained in biological pathways, has enabled the use of targeted protein quantitation for monitoring fold changes in expression as well as biomarker discovery...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28187708/incorporating-prior-biological-knowledge-for-network-based-differential-gene-expression-analysis-using-differentially-weighted-graphical-lasso
#17
Yiming Zuo, Yi Cui, Guoqiang Yu, Ruijiang Li, Habtom W Ressom
BACKGROUND: Conventional differential gene expression analysis by methods such as student's t-test, SAM, and Empirical Bayes often searches for statistically significant genes without considering the interactions among them. Network-based approaches provide a natural way to study these interactions and to investigate the rewiring interactions in disease versus control groups. In this paper, we apply weighted graphical LASSO (wgLASSO) algorithm to integrate a data-driven network model with prior biological knowledge (i...
February 10, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28186866/toward-postgenomics-ophthalmology-a-proteomic-map-of-the-human-choroid-retinal-pigment-epithelium-tissue
#18
Manjunath Dammalli, Krishna R Murthy, Sneha M Pinto, Kalpana Babu Murthy, Raja Sekhar Nirujogi, Anil K Madugundu, Gourav Dey, Bipin Nair, Harsha Gowda, Thottethodi Subrahmanya Keshava Prasad
Ophthalmology and visual health research have received relatively limited attention from the personalized medicine community, but this trend is rapidly changing. Postgenomics technologies such as proteomics are being utilized to establish a baseline biological variation map of the human eye and related tissues. In this context, the choroid is the vascular layer situated between the outer sclera and the inner retina. The choroidal circulation serves the photoreceptors and retinal pigment epithelium (RPE). The RPE is a layer of cuboidal epithelial cells adjacent to the neurosensory retina and maintains the outer limit of the blood-retina barrier...
February 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28185154/the-role-of-adipocytokines-in-coronary-atherosclerosis
#19
REVIEW
Luca Liberale, Aldo Bonaventura, Alessandra Vecchiè, Casula Matteo, Franco Dallegri, Fabrizio Montecucco, Federico Carbone
PURPOSE OF REVIEW: The aim of this review is to overview the pathophysiological role of adipocytokines in atherogenesis, focusing on their potential role as biomarkers of coronary disease. RECENT FINDINGS: Several lines of evidence indicated adipose tissue not only as depot but rather as an endocrine organ. In this context, the balance between pro- and anti-inflammatory adipocytokines has been shown to critically regulate vascular homeostasis in both physiological and pathophysiological conditions...
February 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28181877/an-in-silico-biomarker-based-method-for-the-evaluation-of-virtual-neuropsychiatric-drug-effects
#20
Peter J Siekmeier
The recent explosion in neuroscience research has markedly increased our understanding of the neurobiological correlates of many psychiatric illnesses, but this has unfortunately not translated into more effective pharmacologic treatments for these conditions. At the same time, researchers have increasingly sought out biological markers, or biomarkers, as a way to categorize psychiatric illness, as these are felt to be closer to underlying genetic and neurobiological vulnerabilities. While biomarker-based drug discovery approaches have tended to employ in vivo (e...
February 9, 2017: Neural Computation
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