DNA microarray integromics analysis platform

Background: The study of interactions between molecules belonging to different biochemical families (such as lipids and nucleic acids) requires specialized data analysis methods. This article describes the DNA Microarray Integromics Analysis Platform, a unique web application that focuses on computational integration and analysis of "multi-omics" data. Our tool supports a range of complex analyses, including - among others - low- and high-level analyses of DNA microarray data, integrated analysis of transcriptomics and lipidomics data and the ability to infer miRNA-mRNA interactions. Results: We demonstrate the characteristics and benefits of the DNA Microarray Integromics Analysis Platform using two different test cases. The first test case involves the analysis of the nutrimouse dataset, which contains measurements of the expression of genes involved in nutritional problems and the concentrations of hepatic fatty acids. The second test case involves the analysis of miRNA-mRNA interactions in polysaccharide-stimulated human dermal fibroblasts infected with porcine endogenous retroviruses. Conclusions: The DNA Microarray Integromics Analysis Platform is a web-based graphical user interface for "multi-omics" data management and analysis. Its intuitive nature and wide range of available workflows make it an effective tool for molecular biology research. The platform is hosted at https://lifescience.plgrid.pl

Embracing an integromic approach to tissue biomarker research in cancer: Perspectives and lessons learned.

Modern approaches to biomedical research and diagnostics targeted towards precision medicine are generating ‘big data’ across a range of high-throughput experimental and analytical platforms. Integrative analysis of this rich clinical, pathological, molecular and imaging data represents one of the greatest bottlenecks in biomarker discovery research in cancer and other diseases. Following on from the publication of our successful framework for multimodal data amalgamation and integrative analysis, Pathology Integromics in Cancer (PICan), this article will explore the essential elements of assembling an integromics framework from a more detailed perspective. PICan, built around a relational database storing curated multimodal data, is the research tool sitting at the heart of our interdisciplinary efforts to streamline biomarker discovery and validation. While recognizing that every institution has a unique set of priorities and challenges, we will use our experiences with PICan as a case study and starting point, rationalizing the design choices we made within the context of our local infrastructure and specific needs, but also highlighting alternative approaches that may better suit other programmes of research and discovery. Along the way, we stress that integromics is not just a set of tools, but rather a cohesive paradigm for how modern bioinformatics can be enhanced. Successful implementation of an integromics framework is a collaborative team effort that is built with an eye to the future and greatly accelerates the processes of biomarker discovery, validation and translation into clinical practice

Proteomic approach to investigate the impact of dietary supplementation on lamb meat quality

L'utilizzo di sottoprodotti agroindustriali nell’alimentazione animale può rappresentare una strategia sostenibile per migliorare il benessere degli animali da reddito e la qualità dei loro prodotti. È noto che i sottoprodotti agroindustriali, grazie all'elevata concentrazione di composti bioattivi, rappresentano una risorsa efficace per migliorare la qualità nutrizionale e organolettica della carne. Pertanto, la presente tesi si è proposta di indagare gli effetti dell'inclusione di sottoprodotti agroindustriali, nello specifico buccia di nocciola, nella dieta degli agnelli sulla qualità della carne e sulle variazioni del proteoma durante la conservazione (1, 4 e 7 giorni). In particolare, la presente tesi si è articolata in tre prove sperimentali. Nella prima prova, è stato valutato l'effetto dell'inclusione della buccia di nocciola sul colore della carne e sul proteoma sarcoplasmatico; nella seconda sono stati esaminati i cambiamenti nella texture della carne e nel proteoma miofibrillare. Nel corso della terza prova sono stati applicati approcci proteomici (SDS-PAGE, 2DE e Western Blotting) e bioinformatici per approfondire la comprensione dei meccanismi molecolari coinvolti nei processi post-mortem legati alla strategia di alimentazione. La prova sperimentale della durata di 8 settimane è stata condotta su 22 agnelli (2 mesi di età) Valle del Belice equamente distribuiti in 2 gruppi omogenei. Il gruppo di controllo (C) ha ricevuto una dieta di base, mentre il gruppo nocciola (H) è stato alimentato con la stessa dieta, ma 150 g/kg di sostanza secca sono stati sostituiti con buccia di nocciola. La carne di agnello alimentato con bucce di nocciola è apparsa più tenera, come dimostrato dall’aumento maggiore e più rapido dei valori di indice di frammentazione miofibrillare (MFI). Inoltre, il trattamento con buccia di nocciole ha prodotto carne con una migliore stabilità del colore, come evidenziato dalla più bassa diminuzione dell'indice di rosso e di saturazione. L'approccio proteomico applicato in questo studio ha dimostrato che diverse vie sono coinvolte nei processi post- mortem legati alla tenerezza e alla stabilità del colore nella carne di agnello del gruppo nocciola. Il processo basato sui filamenti di actina, il metabolismo energetico e le proteine associate, le proteine dello stress ossidativo, seguite dalle proteine da shock termico e dal sistema immunitario ed endocrino sono le principali vie che potrebbero agire come potenziali biomarcatori della tenerezza e della stabilità del colore della carne di agnello. I dati hanno evidenziato che ACTA1, HSPB1, TPI1, PARK7, e PRDX6 potrebbero essere considerati biomarcatori affidabili della stabilità del colore e della tenerezza della carne di agnello, come riportato per altre specie animali. In questo studio, undici proteine, tra cui GSTM1, GSTM3, GSTM5, MTX2, GNB1, GBN2, DDAH1, POLR2G, ADIPOQ, APOA1 e SERPINA1, sono state associate per la prima volta come biomarcatori delle caratteristiche qualitative della carne di agnello. I risultati di questo lavoro di tesi evidenziano che il monitoraggio dei biomarcatori proteici rappresenta un valido strumento per predire gli effetti delle strategie alimentari sulla qualità totale della carne.The use of agro-industrial by-products in animal feeding systems can be a potential sustainable strategy for improving animal welfare and product quality. It is well known that by-products, due to the high concentration of bioactive compounds, represent an effective resource in enhancing nutritional and organoleptic meat quality. Therefore, the present thesis aimed to investigate the effects of the inclusion of agro-industrial by-products, specifically hazelnut skin, in the lambs’ diet on meat quality and the changes in the muscle proteome during post-mortem storage (1, 4, and 7 days). Particularly, it is composed of three trials. In the first trial, the effect of the dietary inclusion on meat color characteristics and sarcoplasmic proteome has been assessed, while the changes in meat texture and in the myofibrillar proteome were examined in the second trial. Furthermore, in the third trial proteomics and bioinformatics approaches have been applied to a deeper understanding of the molecular mechanisms involved in the post-mortem processes related to feeding strategies. The experiment was performed on 22 Valle del Belice lambs (2 months of age) equally distributed in 2 homogeneous groups for a duration of 8 weeks. The control group (C) received a basal diet, while the hazelnut group (H) were fed the same diet, but 150 g/kg dry matter of maize was replaced with hazelnut skin. Meat from lamb fed hazelnut skins appeared more tender evidenced by a major and more rapid increase in myofibrillar fragmentation index (MFI). Furthermore, hazelnut dietary treatment produced meat with better color stability as evidenced by the lowest decrease in redness and saturation index found. The proteomic approach applied in this study demonstrated that several pathways are involved in the post-mortem processes linked with tenderness and color stability in meat from lamb feed with hazelnut skin. Actin filament-based process, energy metabolism, associated proteins, oxidative stress proteins, followed by heat shock proteins, and the immune and endocrine system are the main pathways that could act as potential predictors of lamb meat tenderization and color stability. Data evidenced that ACTA1, HSPB1, TPI1, PARK7, and PRDX6 might be considered reliable biomarkers of color stability and tenderness in lamb meat, as reported in the meat of other species. Eleven proteins, these being GSTM1, GSTM3, GSTM5, MTX2, GNB1, GBN2, DDAH1, POLR2G, ADIPOQ, APOA1, and SERPINA1, were not previously detected as predictors of lamb meat quality characteristics, therefore there is a need to validate these novel biomarker candidates using other high-throughput techniques. In conclusion, our findings underline that monitoring protein biomarkers could offer a way to predict the effect of animal feeding strategies thus improving the total meat quality

IDENTIFICATION AND CHARACTERIZATION OF PATHWAYS REGULATED BY KDM4B IN OVARIAN CANCER

KDM4B is a hypoxia-inducible, histone lysine demethylase responsible for primarily demethylating H3K9 and H3K36. This enzyme has been implicated in the literature as a contributor to tumorigenesis in many solid tumor models. Multiple factors contribute to the aggressiveness of ovarian cancer, including hypoxia-induced mechanisms. Establishing the tumorigenic mechanisms regulated by KDM4B provide novel epigenetic links between the hypoxic tumor microenvironment and Epithelial Ovarian Cancer (EOC) progression. This body of work established the in vitro and in vivo relevance of KDM4B in EOC, connecting expression to increased tumorigenesis. KDM4B is expressed in patient primary and metastatic tumors, correlating with hypoxic regions identified by CA-IX. Additionally, KDM4B is robustly induced in EOC cell lines exposed to hypoxia. KDM4B regulates expression of metastatic genes in a demethylase-dependent manner, including LOXL2, LCN2, and PDGFB. KDM4B expression correlates with increased ovarian cancer cell invasion, migration and attachment-free growth in vitro. Intraperitoneal xenograft models demonstrated KDM4B expression corresponded with increased peritoneal dissemination in vivo. Further mechanistic analysis has identified a possible link between KDM4B expression and another epigenetic regulator ARID5B. Functional analysis demonstrates KDM4B participates in secretion of factors contributing to metastasis and tumor progression. 3-Dimensional in vitro functional analysis suggests KDM4B contributes to increased spheroid invasion on Type I Collagen. This project highlights some of the first studies demonstrating that a Jumonji-domain histone demethylase regulates cellular processes required for peritoneal dissemination of EOC. The following observations provide additional knowledge regarding KDM4B activity and its influence in EOC models. These findings provide a better understanding of KDM4B, its activity, and the role it plays in regulating the epigenetic landscape in tumors. The mechanistic and functional pathways regulated by KDM4B may present novel opportunities to develop combinatorial therapies to improve existing therapies for EOC patients

Using MapReduce Streaming for Distributed Life Simulation on the Cloud

Distributed software simulations are indispensable in the study of large-scale life models but often require the use of technically complex lower-level distributed computing frameworks, such as MPI. We propose to overcome the complexity challenge by applying the emerging MapReduce (MR) model to distributed life simulations and by running such simulations on the cloud. Technically, we design optimized MR streaming algorithms for discrete and continuous versions of Conway’s life according to a general MR streaming pattern. We chose life because it is simple enough as a testbed for MR’s applicability to a-life simulations and general enough to make our results applicable to various lattice-based a-life models. We implement and empirically evaluate our algorithms’ performance on Amazon’s Elastic MR cloud. Our experiments demonstrate that a single MR optimization technique called strip partitioning can reduce the execution time of continuous life simulations by 64%. To the best of our knowledge, we are the first to propose and evaluate MR streaming algorithms for lattice-based simulations. Our algorithms can serve as prototypes in the development of novel MR simulation algorithms for large-scale lattice-based a-life models.https://digitalcommons.chapman.edu/scs_books/1014/thumbnail.jp

Circadian and ultradian rhythms depend on the level of consciousness in disorders of consciousness

peer reviewedBackground and aims: Eye opening in patients with disorders of consciousness (DOC) marks the onset of a cyclic pattern with and without arousal. In minimally conscious state (MCS) arousal may be accompanied with awareness, unlike in unresponsive wakefulness syndrome (UWS). The presence of circadian and/or ultradian rhythmicity in patients with DOC has not been well established. To this end, we analyzed actigraphy data with a method well-suited to account for the variable rhythms within and across days observed in this population. Methods: We collected actigraphy data from 73 subjects (19 controls, 35 MCS, 19 UWS) over seven days and performed analyses using PyActigraphy. Singular Spectrum Analysis, a data-driven technique, was used to decompose the signal into circadian and ultradian rhythms. Next, we will evaluate these results statistically and correlate patients’ clinical diagnoses using the Coma Recovery Scale-Revised with the phase of detected circadian rhythms. Results: Data cleaning resulted in exclusion of one control (5.3%), 10 MCS (28.6%) and nine UWS (45%) subject(s). Our preliminary results show that the strength of circadian and ultradian rhythms in actigraphy data decreases with consciousness from healthy controls to MCS and almost disappearing in UWS (Figure 1).Conclusion: Preservation of circadian/ultradian rhythms seems associated with the level of consciousness. Rhythms appear almost absent in UWS patients, which suggests limited behavioral evidence for a sleep/wake cycle although eye opening is observed. Overall, the use of actigraphy could contribute to clinical assessments in DOC, and although data quality might be suboptimal, acquisition can be repeated easily