26 research outputs found
FlowDiv: A new pipeline for analyzing flow cytometric diversity
Background: Flow cytometry (FCM) is one of the most commonly used technologies for analysis of numerous biological systems at the cellular level, from cancer cells to microbial communities. Its high potential and wide applicability led to the development of various analytical protocols, which are often not interchangeable between fields of expertise. Environmental science in particular faces difficulty in adapting to non-specific protocols, mainly because of the highly heterogeneous nature of environmental samples. This variety, although it is intrinsic to environmental studies, makes it difficult to adjust analytical protocols to maintain both mathematical formalism and comprehensible biological interpretations, principally for questions that rely on the evaluation of differences between cytograms, an approach also termed cytometric diversity. Despite the availability of promising bioinformatic tools conceived for or adapted to cytometric diversity, most of them still cannot deal with common technical issues such as the integration of differently acquired datasets, the optimal number of bins, and the effective correlation of bins to previously known cytometric populations. Results: To address these and other questions, we have developed flowDiv, an R language pipeline for analysis of environmental flow cytometry data. Here, we present the rationale for flowDiv and apply the method to a real dataset from 31 freshwater lakes in Patagonia, Argentina, to reveal significant aspects of their cytometric diversities. Conclusions: flowDiv provides a rather intuitive way of proceeding with FCM analysis, as it combines formal mathematical solutions and biological rationales in an intuitive framework specifically designed to explore cytometric diversity.Fil: Wanderley, Bruno M. S.. Universidade Federal do Rio Grande do Norte; BrasilFil: Araújo, Daniel S.. Universidade Federal do Rio Grande do Norte; BrasilFil: Quiroga, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Amado, André M.. Universidade Federal do Rio Grande do Norte; Brasil. Universidade Federal de Juiz de Fora; BrasilFil: Neto, Adrião D. D.. Universidade Federal do Rio Grande do Norte; BrasilFil: Sarmento, Hugo. Universidade Federal do São Carlos; BrasilFil: Metz, Sebastián Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Unrein, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentin
Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle
Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying
mechanisms of synaptic plasticity are poorly understood. The central controversy is on
whether long-term potentiation (LTP) takes a role during sleep and which would be its specific
effect on memory. To address this question, we used immunohistochemistry to measure
phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat
hippocampus immediately after specific sleep-wake states were interrupted. Control animals
not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels
across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during
subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement
sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles
near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on
a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus
across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights
to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM
transition led to marked swaps in synaptic weight ranking. To better understand the interaction
between rescaling and restructuring during sleep, we implemented synaptic homeostasis
and embossing in a detailed hippocampal-cortical model with both excitatory and
inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation
and strengthening depression, while synaptic embossing was simulated by evoking LTP
on selected synapses. We observed that synaptic homeostasis facilitates controlled
synaptic restructuring. The results imply a mechanism for a cognitive synergy between
SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect
of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic
restructuring.: Support obtained from Financiadora de
Estudos e Projetos (http://www.finep.gov.br/) Grant #
01.06.1092.00 to SR; Conselho Nacional de
Desenvolvimento Científico e Tecnológico (http://
www.cnpq.br/): Grants 481506/2007-1, 481351/2011-
6 and 306604/2012-4 to SR, Coordenação de
Aperfeiçoamento de Pessoal de Nível Superior
(http://www.capes.gov.br/) and Ciencias sem
Fronteiras (http://www.cienciasemfronteiras.gov.br/
web/csf/home) to AT and CRC; Fundação de Amparo
à Pesquisa do Rio Grande do Norte (http://wwwfapern.rn.gov.br/): Grant Pronem 003/2011 to SR;
Fundação de Amparo à Pesquisa do Estado de São
Paulo (http://www.fapesp.br/): Grant #2013/ 07699-0 -
Center for Neuromathematics to SR; CMP and VRC
supported by post-doctoral fellowships from
Fundação de Amparo à Pesquisa do Rio Grande do
Norte /CNPq. Additional support obtained from the
Federal University of Rio Grande do Norte (www.ufrn.
br); Ministry of Science, Technology and Innovation
(http://www.mcti.gov.br/); Associação Alberto Santos
Dumont de Apoio à Pesquisa (http://natalneuro.com/
associacao/index.asp); Pew Latin American Fellows
Program (http://www.pewtrusts.org/en/projects/pewlatin-american-fellows/)
to SR; Informatics
Department of the Instituto Federal de Educação,
Ciência e Tecnologia do Rio Grande do Norte (http://
portal.ifrn.edu.br/) to WB. The funders had no role in
study design, data collection and analysis, decision to
publish, or preparation of the manuscrip
An Analysis of Information Dynamic Behavior Using Autoregressive Models
Information Theory is a branch of mathematics, more specifically probability theory, that studies information quantification. Recently, several researches have been successful with the use of Information Theoretic Learning (ITL) as a new technique of unsupervised learning. In these works, information measures are used as criterion of optimality in learning. In this article, we will analyze a still unexplored aspect of these information measures, their dynamic behavior. Autoregressive models (linear and non-linear) will be used to represent the dynamics in information measures. As a source of dynamic information, videos with different characteristics like fading, monotonous sequences, etc., will be used
Classification System of Pathological Voices Using Correntropy
This paper proposes the use of a similarity measure based on information theory called correntropy for the automatic classification of pathological voices. By using correntropy, it is possible to obtain descriptors that aggregate distinct spectral characteristics for healthy and pathological voices. Experiments using computational simulation demonstrate that such descriptors are very efficient in the characterization of vocal dysfunctions, leading to a success rate of 97% in the classification. With this new architecture, the classification process of vocal pathologies becomes much more simple and efficient
A Novel Machine Learning 13-Gene Signature: Improving Risk Analysis and Survival Prediction for Clear Cell Renal Cell Carcinoma Patients
Patients with clear cell renal cell carcinoma (ccRCC) have poor survival outcomes, especially if it has metastasized. It is of paramount importance to identify biomarkers in genomic data that could help predict the aggressiveness of ccRCC and its resistance to drugs. Thus, we conducted a study with the aims of evaluating gene signatures and proposing a novel one with higher predictive power and generalization in comparison to the former signatures. Using ccRCC cohorts of the Cancer Genome Atlas (TCGA-KIRC) and International Cancer Genome Consortium (ICGC-RECA), we evaluated linear survival models of Cox regression with 14 signatures and six methods of feature selection, and performed functional analysis and differential gene expression approaches. In this study, we established a 13-gene signature (AR, AL353637.1, DPP6, FOXJ1, GNB3, HHLA2, IL4, LIMCH1, LINC01732, OTX1, SAA1, SEMA3G, ZIC2) whose expression levels are able to predict distinct outcomes of patients with ccRCC. Moreover, we performed a comparison between our signature and others from the literature. The best-performing gene signature was achieved using the ensemble method Min-Redundancy and Max-Relevance (mRMR). This signature comprises unique features in comparison to the others, such as generalization through different cohorts and being functionally enriched in significant pathways: Urothelial Carcinoma, Chronic Kidney disease, and Transitional cell carcinoma, Nephrolithiasis. From the 13 genes in our signature, eight are known to be correlated with ccRCC patient survival and four are immune-related. Our model showed a performance of 0.82 using the Receiver Operator Characteristic (ROC) Area Under Curve (AUC) metric and it generalized well between the cohorts. Our findings revealed two clusters of genes with high expression (SAA1, OTX1, ZIC2, LINC01732, GNB3 and IL4) and low expression (AL353637.1, AR, HHLA2, LIMCH1, SEMA3G, DPP6, and FOXJ1) which are both correlated with poor prognosis. This signature can potentially be used in clinical practice to support patient treatment care and follow-up
Osteoporosis screening using machine learning and electromagnetic waves
Abstract Osteoporosis is a disease characterized by impairment of bone microarchitecture that causes high socioeconomic impacts in the world because of fractures and hospitalizations. Although dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing the disease, access to DXA in developing countries is still limited due to its high cost, being present only in specialized hospitals. In this paper, we analyze the performance of Osseus, a low-cost portable device based on electromagnetic waves that measures the attenuation of the signal that crosses the medial phalanx of a patient’s middle finger and was developed for osteoporosis screening. The analysis is carried out by predicting changes in bone mineral density using Osseus measurements and additional common risk factors used as input features to a set of supervised classification models, while the results from DXA are taken as target (real) values during the training of the machine learning algorithms. The dataset consisted of 505 patients who underwent osteoporosis screening with both devices (DXA and Osseus), of whom 21.8% were healthy and 78.2% had low bone mineral density or osteoporosis. A cross-validation with k-fold = 5 was considered in model training, while 20% of the whole dataset was used for testing. The obtained performance of the best model (Random Forest) presented a sensitivity of 0.853, a specificity of 0.879, and an F1 of 0.859. Since the Random Forest (RF) algorithm allows some interpretability of its results (through the impurity check), we were able to identify the most important variables in the classification of osteoporosis. The results showed that the most important variables were age, body mass index, and the signal attenuation provided by Osseus. The RF model, when used together with Osseus measurements, is effective in screening patients and facilitates the early diagnosis of osteoporosis. The main advantages of such early screening are the reduction of costs associated with exams, surgeries, treatments, and hospitalizations, as well as improved quality of life for patients
Statistics of real spikes from the hippocampal CA1 field during WK, SWS or REM.
<p>(A) Probability distributions of spike rates across states, with mean population values represented by dashed lines (left panel). Mean and variance of spike rates recorded during each state (right panel). (B) Square matrix of Pearson's linear correlation coefficient for spiking of 45 neurons during WK, SWS or REM (left panel), and the corresponding mean and variance (left panel). Significant differences of the Pearson's coefficient distribution were found between WK and SWS (Kolmogorov-Smirnov (KS) p = 6.9607e-023), WK and REM (KS, p = 1.0890e-023), and SWS and REM (p = 4.0259e-017). (C) Distribution of durations for intervals separating consecutive REM episodes (left panel, n = 6 rats; 28.8 hours of recordings). Cumulative plot of the REM-to-REM interval durations (right panel). Note that 91.6% of the intervals are shorter than 30 min (dashed line). More examples in <b><a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004241#pcbi.1004241.s010" target="_blank">S4 Fig</a></b>; see also <b><a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004241#pcbi.1004241.s017" target="_blank">S1 Table</a></b>.</p