scholarly journals Integrating GWAS and Expression Data for Functional Characterization of Disease-Associated SNPs: An Application to Follicular Lymphoma

2013 ◽  
Vol 92 (1) ◽  
pp. 126-130 ◽  
Author(s):  
Lucia Conde ◽  
Paige M. Bracci ◽  
Rhea Richardson ◽  
Stephen B. Montgomery ◽  
Christine F. Skibola
Author(s):  
Yuna Blum ◽  
Magalie Houée-Bigot ◽  
David Causeur

AbstractInference on gene regulatory networks from high-throughput expression data turns out to be one of the main current challenges in systems biology. Such networks can be very insightful for the deep understanding of interactions between genes. Because genes-gene interactions is often viewed as joint contributions to known biological mechanisms, inference on the dependence among gene expressions is expected to be consistent to some extent with the functional characterization of genes which can be derived from ontologies (GO, KEGG, …). The present paper introduces a sparse factor model as a general framework either to account for a prior knowledge on joint contributions of modules of genes to latent biological processes or to infer on the corresponding co-expression network. We propose an


Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1029 ◽  
Author(s):  
Tatyana I. Odintsova ◽  
Marina P. Slezina ◽  
Ekaterina A. Istomina

The grass family (Poaceae) is one of the largest families of flowering plants, growing in all climatic zones of all continents, which includes species of exceptional economic importance. The high adaptability of grasses to adverse environmental factors implies the existence of efficient resistance mechanisms that involve the production of antimicrobial peptides (AMPs). Of plant AMPs, defensins represent one of the largest and best-studied families. Although wheat and barley seed γ-thionins were the first defensins isolated from plants, the functional characterization of grass defensins is still in its infancy. In this review, we summarize the current knowledge of the characterized defensins from cultivated and selected wild-growing grasses. For each species, isolation of defensins or production by heterologous expression, peptide structure, biological activity, and structure–function relationship are described, along with the gene expression data. We also provide our results on in silico mining of defensin-like sequences in the genomes of all described grass species and discuss their potential functions. The data presented will form the basis for elucidation of the mode of action of grass defensins and high adaptability of grasses to environmental stress and will provide novel potent molecules for practical use in medicine and agriculture.


2018 ◽  
Vol 16 (11) ◽  
pp. 1825-1835 ◽  
Author(s):  
Zixiang Wen ◽  
Ruijuan Tan ◽  
Shichen Zhang ◽  
Paul J. Collins ◽  
Jiazheng Yuan ◽  
...  

2019 ◽  
Vol 17 (04) ◽  
pp. 1950025 ◽  
Author(s):  
Sovan Saha ◽  
Abhimanyu Prasad ◽  
Piyali Chatterjee ◽  
Subhadip Basu ◽  
Mita Nasipuri

Computational prediction of functional annotation of proteins is an uphill task. There is an ever increasing gap between functional characterization of protein sequences and deluge of protein sequences generated by large-scale sequencing projects. The dynamic nature of protein interactions is frequently observed which is mostly influenced by any new change of state or change in stimuli. Functional characterization of proteins can be inferred from their interactions with each other, which is dynamic in nature. In this work, we have used a dynamic protein–protein interaction network (PPIN), time course gene expression data and protein sequence information for prediction of functional annotation of proteins. During progression of a particular function, it has also been observed that not all the proteins are active at all time points. For unannotated active proteins, our proposed methodology explores the dynamic PPIN consisting of level-1 and level-2 neighboring proteins at different time points, filtered by Damerau–Levenshtein edit distance to estimate the similarity between two protein sequences and coefficient variation methods to assess the strength of an edge in a network. Finally, from the filtered dynamic PPIN, at each time point, functional annotations of the level-2 proteins are assigned to the unknown and unannotated active proteins through the level-1 neighbor, following a bottom-up strategy. Our proposed methodology achieves an average precision, recall and F-Score of 0.59, 0.76 and 0.61 respectively, which is significantly higher than the reported state-of-the-art methods.


2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.


1998 ◽  
Vol 79 (01) ◽  
pp. 177-185 ◽  
Author(s):  
Ashia Siddiqua ◽  
Michael Wilkinson ◽  
Vijay Kakkar ◽  
Yatin Patel ◽  
Salman Rahman ◽  
...  

SummaryWe report the characterization of a monoclonal antibody (MAb) PM6/13 which recognises glycoprotein IIIa (GPIIIa) on platelet membranes and in functional studies inhibits platelet aggregation induced by all agonists examined. In platelet-rich plasma, inhibition of aggregation induced by ADP or low concentrations of collagen was accompanied by inhibition of 5-hydroxytryptamine secretion. EC50 values were 10 and 9 [H9262]g/ml antibody against ADP and collagen induced responses respectively. In washed platelets treated with the cyclooxygenase inhibitor, indomethacin, PM6/13 inhibited platelet aggregation induced by thrombin (0.2 U/ml), collagen (10 [H9262]g/ml) and U46619 (3 [H9262]M) with EC50 = 4, 8 and 4 [H9262]g/ml respectively, without affecting [14C]5-hydroxytryptamine secretion or [3H]arachidonate release in appropriately labelled cells. Studies in Fura 2-labelled platelets revealed that elevation of intracellular calcium by ADP, thrombin or U46619 was unaffected by PM6/13 suggesting that the epitope recognised by the antibody did not influence Ca2+ regulation. In agreement with the results from the platelet aggregation studies, PM6/13 was found to potently inhibit binding of 125I-fibrinogen to ADP activated platelets. Binding of this ligand was also inhibited by two other MAbs tested, namely SZ-21 (also to GPIIIa) and PM6/248 (to the GPIIb-IIIa complex). However when tested against binding of 125I-fibronectin to thrombin stimulated platelets, PM6/13 was ineffective in contrast with SZ-21 and PM6/248, that were both potent inhibitors. This suggested that the epitopes recognised by PM6/13 and SZ-21 on GPIIIa were distinct. Studies employing proteolytic dissection of 125I-labelled GPIIIa by trypsin followed by immunoprecipitation with PM6/13 and analysis by SDS-PAGE, revealed the presence of four fragments at 70, 55, 30 and 28 kDa. PM6/13 did not recognize any protein bands on Western blots performed under reducing conditions. However Western blotting analysis with PM6/13 under non-reducing conditions revealed strong detection of the parent GP IIIa molecule, of trypsin treated samples revealed recognition of an 80 kDa fragment at 1 min, faint recognition of a 60 kDa fragment at 60 min and no recognition of any product at 18 h treatment. Under similar conditions, SZ-21 recognized fragments at 80, 75 and 55 kDa with the 55kDa species persisting even after 18 h trypsin treatment. These studies confirm the epitopes recognised by PM6/13 and SZ-21 to be distinct and that PM6/13 represents a useful tool to differentiate the characteristics of fibrinogen and fibronectin binding to the GPIIb-IIIa complex on activated platelets.


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