scholarly journals Pseudotime estimation: deconfounding single cell time series

2015 ◽  
Author(s):  
John E Reid ◽  
Lorenz Wernisch

Cross-sectional time series single cell data confound several sources of variation, with contributions from measurement noise, stochastic cell to cell variation and cell progression at different rates. Time series from single cell assays are particularly susceptible to confounding as the measurements are not averaged over populations of cells. When several genes are assayed in parallel these effects can be estimated and corrected for under certain smoothness assumptions on cell progression. We present a principled probabilistic model with a Bayesian inference scheme to analyse such data. We demonstrate our method's utility on public microarray, nCounter and RNA-seq data sets from three organisms. Our method almost perfectly recovers withheld capture times in an Arabidopsis data set, it accurately estimates cell cycle peak times in a human prostate cancer cell line and it correctly identifies two precocious cells in a study of paracrine signalling in mouse dendritic cells. Furthermore, our method compares favourably with Monocle, a state-of-the-art technique. We also show using held out data that uncertainty in the temporal dimension is a common confounder and should be accounted for in analyses of cross-sectional time series.

2021 ◽  
Vol 22 (23) ◽  
pp. 12827
Author(s):  
Mahshid Ghasemi ◽  
Tyron Turnbull ◽  
Sonia Sebastian ◽  
Ivan Kempson

The MTT assay for cellular metabolic activity is almost ubiquitous to studies of cell toxicity; however, it is commonly applied and interpreted erroneously. We investigated the applicability and limitations of the MTT assay in representing treatment toxicity, cell viability, and metabolic activity. We evaluated the effect of potential confounding variables on the MTT assay measurements on a prostate cancer cell line (PC-3) including cell seeding number, MTT concentration, MTT incubation time, serum starvation, cell culture media composition, released intracellular contents (cell lysate and secretome), and extrusion of formazan to the extracellular space. We also assessed the confounding effect of polyethylene glycol (PEG)-coated gold nanoparticles (Au-NPs) as a tested treatment in PC-3 cells on the assay measurements. We additionally evaluated the applicability of microscopic image cytometry as a tool for measuring intracellular MTT reduction at the single-cell level. Our findings show that the assay measurements are a result of a complicated process dependant on many of the above-mentioned factors, and therefore, optimization of the assay and rational interpretation of the data is necessary to prevent misleading conclusions on variables such as cell viability, treatment toxicity, and/or cell metabolism. We conclude, with recommendations on how to apply the assay and a perspective on where the utility of the assay is a powerful tool, but likewise where it has limitations.


2015 ◽  
Vol 50 (3) ◽  
pp. 521-548 ◽  
Author(s):  
Carolien van Ham ◽  
Staffan I. Lindberg

Over 90 per cent of the world’s states currently select their national leaders through multiparty elections. However, in Africa the quality of elections still varies widely, ranging from elections plagued by violence and fraud to elections that are relatively ‘free and fair’. Yet, little is known about trade-offs between different strategies of electoral manipulation and the differences between incumbent and opposition actors’ strategies. We theorize that choices for specific types of manipulation are driven by available resources and cost considerations for both incumbents and opposition actors, and are mutually responsive. We also suggest that costs of manipulative strategies are shaped by the level of democratization. We test our hypotheses on a time series, cross-sectional data set with observations for 286 African elections from 1986 to 2012. We find that democratization makes ‘cheap’ forms of electoral manipulation available to incumbents such as intimidation and manipulating electoral administration less viable, thus leading to increases in vote buying. The future of democracy in Africa thus promises elections where the administration of elections becomes better and better but at the same time vote buying will increase. Not all things go together, at least not all the time. The future of democracy in Africa will mean more money in politics, more patronage and more clientelistic offers thrown around, at least in the short to medium term.


2021 ◽  
Vol 7 (1) ◽  
pp. 195-204
Author(s):  
Syed Hamid Ali Shah ◽  
Attaullah Shah ◽  
Muhammad Kamran Khan ◽  
Hamid Ullah

In this study, we try to answer several empirical questions related to testing of asset pricing models in Pakistan. First, we test the assumptions of capital asset pricing model (CAPM) using cross-sectional regression methodology of Fama and MacBeth (FMB) (1973). Second, we test the conditional relationship between beta and expected returns using FMB cross-sectional regressions. Third, we test and compare the explanatory power of CAPM and Fama and French (1993) three factor models using time-series regressions. For all of the above empirical tests, we use sufficiently large data set of weekly data from January 2006 to December 2018 of non-financial firms listed at the Pakistan Stock Exchange. Results of the cross-sectional regressions suggest that beta cannot explain expected returns. However, there is weak evidence that a conditional relation exits between beta and expected returns. Results of the time-series regression suggest that both CAPM and three factor model do well in explaining expected returns. However, GRS-based test of regression intercepts and regressions R2 indicate that Fama and French model better captures variations in observed stock returns than the CAPM.


2021 ◽  
Vol 40 (5) ◽  
pp. 946-963
Author(s):  
Birger Wernerfelt ◽  
Alvin Silk ◽  
Shuyi Yu

In 1956, a group of trade associations representing publishers and independent advertising agencies signed a consent decree aimed at ending a set of trade practices that for half a century effectively precluded advertisers from owning and operating in-house agencies. Since then, large firms have internalized more and more of the services formerly performed by external agencies, perhaps as many as half. We use this phenomenon to test a theory of the firm, thereby simultaneously offering an explanation for it. The theory suggests that firms should internalize activities for which their competitive position implies (1) that it is more important for human capital to be firm specific as opposed to function specific and (2) that frequent modifications are desirable. It also predicts (3) that these two effects reinforce each other. This is the first paper to report on a test of the specialization hypothesis, and we find that it is robustly significant in a cross-sectional data set covering nine different agency activities in 79 firms. In addition to the cross-sectional test, we informally present some time-series data suggesting that both specialization and frequency have grown over time along with the level of internalization.


Crisis ◽  
2013 ◽  
Vol 34 (4) ◽  
pp. 251-261 ◽  
Author(s):  
Joanne N. Luke ◽  
Ian P. Anderson ◽  
Graham J. Gee ◽  
Reg Thorpe ◽  
Kevin G. Rowley ◽  
...  

Background: There has been increasing attention over the last decade on the issue of indigenous youth suicide. A number of studies have documented the high prevalence of suicide behavior and mortality in Australia and internationally. However, no studies have focused on documenting the correlates of suicide behavior for indigenous youth in Australia. Aims: To examine the prevalence of suicide ideation and attempt and the associated factors for a community 1 The term ”community” refers specifically to Koori people affiliated with the Victorian Aboriginal Health Service. cohort of Koori 2 The term ”Koori” refers to indigenous people from the south-eastern region of Australia, including Melbourne. The term ”Aboriginal” has been used when referring to indigenous people from Australia. The term ”indigenous” has been used throughout this article when referring to the first people of a nation within an international context. (Aboriginal) youth. Method: Data were obtained from the Victorian Aboriginal Health Service (VAHS) Young People’s Project (YPP), a community initiated cross-sectional data set. In 1997/1998, self-reported data were collected for 172 Koori youth aged 12–26 years living in Melbourne, Australia. The data were analyzed to assess the prevalence of current suicide ideation and lifetime suicide attempt. Principal components analysis (PCA) was used to identify closely associated social, emotional, behavioral, and cultural variables at baseline and Cox regression modeling was then used to identify associations between PCA components and suicide ideation and attempt. Results: Ideation and attempt were reported at 23.3% and 24.4%, respectively. PCA yielded five components: (1) emotional distress, (2) social distress A, (3) social distress B, (4) cultural connection, (5) behavioral. All were positively and independently associated with suicide ideation and attempt, while cultural connection showed a negative association. Conclusions: Suicide ideation and attempt were common in this cross-section of indigenous youth with an unfavorable profile for the emotional, social, cultural, and behavioral factors.


Author(s):  
Diaz Juan Navia ◽  
Diaz Juan Navia ◽  
Bolaños Nancy Villegas ◽  
Bolaños Nancy Villegas ◽  
Igor Malikov ◽  
...  

Sea Surface Temperature Anomalies (SSTA), in four coastal hydrographic stations of Colombian Pacific Ocean, were analyzed. The selected hydrographic stations were: Tumaco (1°48'N-78°45'W), Gorgona island (2°58'N-78°11'W), Solano Bay (6°13'N-77°24'W) and Malpelo island (4°0'N-81°36'W). SSTA time series for 1960-2015 were calculated from monthly Sea Surface Temperature obtained from International Comprehensive Ocean Atmosphere Data Set (ICOADS). SSTA time series, Oceanic Nino Index (ONI), Pacific Decadal Oscillation index (PDO), Arctic Oscillation index (AO) and sunspots number (associated to solar activity), were compared. It was found that the SSTA absolute minimum has occurred in Tumaco (-3.93°C) in March 2009, in Gorgona (-3.71°C) in October 2007, in Solano Bay (-4.23°C) in April 2014 and Malpelo (-4.21°C) in December 2005. The SSTA absolute maximum was observed in Tumaco (3.45°C) in January 2002, in Gorgona (5.01°C) in July 1978, in Solano Bay (5.27°C) in March 1998 and Malpelo (3.64°C) in July 2015. A high correlation between SST and ONI in large part of study period, followed by a good correlation with PDO, was identified. The AO and SSTA have showed an inverse relationship in some periods. Solar Cycle has showed to be a modulator of behavior of SSTA in the selected stations. It was determined that extreme values of SST are related to the analyzed large scale oscillations.


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