scholarly journals Inferability of transcriptional networks from large scale gene deletion studies

2016 ◽  
Author(s):  
Christopher Frederik Blum ◽  
Nadia Heramvand ◽  
Armin S. Khonsari ◽  
Markus Kollmann

Generating a comprehensive map of molecular interactions in living cells is difficult and great efforts are undertaken to infer molecular interactions from large scale perturbation experiments. Here, we develop the analytical and numerical tools to quantify the fundamental limits for inferring transcriptional networks from gene knockout screens and introduce a network inference method that is unbiased and scalable to large network sizes. We show that it is possible to infer gene regulatory interactions with high statistical significance, even if prior knowledge about potential regulators is absent.

2019 ◽  
Vol 3 (3) ◽  
pp. 827-847 ◽  
Author(s):  
Leonardo Novelli ◽  
Patricia Wollstadt ◽  
Pedro Mediano ◽  
Michael Wibral ◽  
Joseph T. Lizier

Network inference algorithms are valuable tools for the study of large-scale neuroimaging datasets. Multivariate transfer entropy is well suited for this task, being a model-free measure that captures nonlinear and lagged dependencies between time series to infer a minimal directed network model. Greedy algorithms have been proposed to efficiently deal with high-dimensional datasets while avoiding redundant inferences and capturing synergistic effects. However, multiple statistical comparisons may inflate the false positive rate and are computationally demanding, which limited the size of previous validation studies. The algorithm we present—as implemented in the IDTxl open-source software—addresses these challenges by employing hierarchical statistical tests to control the family-wise error rate and to allow for efficient parallelization. The method was validated on synthetic datasets involving random networks of increasing size (up to 100 nodes), for both linear and nonlinear dynamics. The performance increased with the length of the time series, reaching consistently high precision, recall, and specificity (>98% on average) for 10,000 time samples. Varying the statistical significance threshold showed a more favorable precision-recall trade-off for longer time series. Both the network size and the sample size are one order of magnitude larger than previously demonstrated, showing feasibility for typical EEG and magnetoencephalography experiments.


2020 ◽  
Vol 642 ◽  
pp. A24
Author(s):  
Sarah Walsh ◽  
Sheila McBreen ◽  
Antonio Martin-Carrillo ◽  
Thomas Dauser ◽  
Nastasha Wijers ◽  
...  

At low redshifts, the observed baryonic density falls far short of the total number of baryons predicted. Cosmological simulations suggest that these baryons reside in filamentary gas structures, known as the warm-hot intergalactic medium (WHIM). As a result of the high temperatures of these filaments, the matter is highly ionised such that it absorbs and emits far-UV and soft X-ray photons. Athena, the proposed European Space Agency X-ray observatory, aims to detect the “missing” baryons in the WHIM up to redshifts of z = 1 through absorption in active galactic nuclei and gamma-ray burst (GRB) afterglow spectra, allowing for the study of the evolution of these large-scale structures of the Universe. This work simulates WHIM filaments in the spectra of GRB X-ray afterglows with Athena using the SImulation of X-ray TElescopes framework. We investigate the feasibility of their detection with the X-IFU instrument, through O VII (E = 573 eV) and O VIII (E = 674 eV) absorption features, for a range of equivalent widths imprinted onto GRB afterglow spectra of observed starting fluxes ranging between 10−12 and 10−10 erg cm−2 s−1, in the 0.3−10 keV energy band. The analyses of X-IFU spectra by blind line search show that Athena will be able to detect O VII−O VIII absorption pairs with EWO VII > 0.13 eV and EWO VIII > 0.09 eV for afterglows with F > 2 × 10−11 erg cm−2 s−1. This allows for the detection of ≈ 45−137 O VII−O VIII absorbers during the four-year mission lifetime. The work shows that to obtain an O VII−O VIII detection of high statistical significance, the local hydrogen column density should be limited at NH < 8 × 1020 cm−2.


2019 ◽  
Vol 20 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Mariana Jesus ◽  
Tânia Silva ◽  
César Cagigal ◽  
Vera Martins ◽  
Carla Silva

Introduction: The field of nutritional psychiatry is a fast-growing one. Although initially, it focused on the effects of vitamins and micronutrients in mental health, in the last decade, its focus also extended to the dietary patterns. The possibility of a dietary cost-effective intervention in the most common mental disorder, depression, cannot be overlooked due to its potential large-scale impact. Method: A classic review of the literature was conducted, and studies published between 2010 and 2018 focusing on the impact of dietary patterns in depression and depressive symptoms were included. Results: We found 10 studies that matched our criteria. Most studies showed an inverse association between healthy dietary patterns, rich in fruits, vegetables, lean meats, nuts and whole grains, and with low intake of processed and sugary foods, and depression and depressive symptoms throughout an array of age groups, although some authors reported statistical significance only in women. While most studies were of cross-sectional design, making it difficult to infer causality, a randomized controlled trial presented similar results. Discussion: he association between dietary patterns and depression is now well-established, although the exact etiological pathways are still unknown. Dietary intervention, with the implementation of healthier dietary patterns, closer to the traditional ones, can play an important role in the prevention and adjunctive therapy of depression and depressive symptoms. Conclusion: More large-scale randomized clinical trials need to be conducted, in order to confirm the association between high-quality dietary patterns and lower risk of depression and depressive symptoms.


2021 ◽  
pp. 1-8
Author(s):  
Regina Sá ◽  
Tiago Pinho-Bandeira ◽  
Guilherme Queiroz ◽  
Joana Matos ◽  
João Duarte Ferreira ◽  
...  

<b><i>Background:</i></b> Ovar was the first Portuguese municipality to declare active community transmission of SARS-CoV-2, with total lockdown decreed on March 17, 2020. This context provided conditions for a large-scale testing strategy, allowing a referral system considering other symptoms besides the ones that were part of the case definition (fever, cough, and dyspnea). This study aims to identify other symptoms associated with COVID-19 since it may clarify the pre-test probability of the occurrence of the disease. <b><i>Methods:</i></b> This case-control study uses primary care registers between March 29 and May 10, 2020 in Ovar municipality. Pre-test clinical and exposure-risk characteristics, reported by physicians, were collected through a form, and linked with their laboratory result. <b><i>Results:</i></b> The study population included a total of 919 patients, of whom 226 (24.6%) were COVID-19 cases and 693 were negative for SARS-CoV-2. Only 27.1% of the patients reporting contact with a confirmed or suspected case tested positive. In the multivariate analysis, statistical significance was obtained for headaches (OR 0.558), odynophagia (OR 0.273), anosmia (OR 2.360), and other symptoms (OR 2.157). The interaction of anosmia and odynophagia appeared as possibly relevant with a borderline statistically significant OR of 3.375. <b><i>Conclusion:</i></b> COVID-19 has a wide range of symptoms. Of the myriad described, the present study highlights anosmia itself and calls for additional studies on the interaction between anosmia and odynophagia. Headaches and odynophagia by themselves are not associated with an increased risk for the disease. These findings may help clinicians in deciding when to test, especially when other diseases with similar symptoms are more prevalent, namely in winter.


2016 ◽  
Vol 12 (2) ◽  
pp. 588-597 ◽  
Author(s):  
Jun Wu ◽  
Xiaodong Zhao ◽  
Zongli Lin ◽  
Zhifeng Shao

Transcriptional regulation is a basis of many crucial molecular processes and an accurate inference of the gene regulatory network is a helpful and essential task to understand cell functions and gain insights into biological processes of interest in systems biology.


2011 ◽  
Vol 6 (2) ◽  
pp. 252-277 ◽  
Author(s):  
Stephen T. Ziliak

AbstractStudent's exacting theory of errors, both random and real, marked a significant advance over ambiguous reports of plant life and fermentation asserted by chemists from Priestley and Lavoisier down to Pasteur and Johannsen, working at the Carlsberg Laboratory. One reason seems to be that William Sealy Gosset (1876–1937) aka “Student” – he of Student'st-table and test of statistical significance – rejected artificial rules about sample size, experimental design, and the level of significance, and took instead an economic approach to the logic of decisions made under uncertainty. In his job as Apprentice Brewer, Head Experimental Brewer, and finally Head Brewer of Guinness, Student produced small samples of experimental barley, malt, and hops, seeking guidance for industrial quality control and maximum expected profit at the large scale brewery. In the process Student invented or inspired half of modern statistics. This article draws on original archival evidence, shedding light on several core yet neglected aspects of Student's methods, that is, Guinnessometrics, not discussed by Ronald A. Fisher (1890–1962). The focus is on Student's small sample, economic approach to real error minimization, particularly in field and laboratory experiments he conducted on barley and malt, 1904 to 1937. Balanced designs of experiments, he found, are more efficient than random and have higher power to detect large and real treatment differences in a series of repeated and independent experiments. Student's world-class achievement poses a challenge to every science. Should statistical methods – such as the choice of sample size, experimental design, and level of significance – follow the purpose of the experiment, rather than the other way around? (JEL classification codes: C10, C90, C93, L66)


2021 ◽  
Vol 34 (10) ◽  
pp. 4043-4068
Author(s):  
Liming Zhou ◽  
Yuhong Tian ◽  
Nan Wei ◽  
Shu-peng Ho ◽  
Jing Li

AbstractTurbulent mixing in the planetary boundary layer (PBL) governs the vertical exchange of heat, moisture, momentum, trace gases, and aerosols in the surface–atmosphere interface. The PBL height (PBLH) represents the maximum height of the free atmosphere that is directly influenced by Earth’s surface. This study uses a multidata synthesis approach from an ensemble of multiple global datasets of radiosonde observations, reanalysis products, and climate model simulations to examine the spatial patterns of long-term PBLH trends over land between 60°S and 60°N for the period 1979–2019. By considering both the sign and statistical significance of trends, we identify large-scale regions where the change signal is robust and consistent to increase our confidence in the obtained results. Despite differences in the magnitude and sign of PBLH trends over many areas, all datasets reveal a consensus on increasing PBLH over the enormous and very dry Sahara Desert and Arabian Peninsula (SDAP) and declining PBLH in India. At the global scale, the changes in PBLH are significantly correlated positively with the changes in surface heating and negatively with the changes in surface moisture, consistent with theory and previous findings in the literature. The rising PBLH is in good agreement with increasing sensible heat and surface temperature and decreasing relative humidity over the SDAP associated with desert amplification, while the declining PBLH resonates well with increasing relative humidity and latent heat and decreasing sensible heat and surface warming in India. The PBLH changes agree with radiosonde soundings over the SDAP but cannot be validated over India due to lack of good-quality radiosonde observations.


1993 ◽  
Vol 27 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Oswaldo Paulo Forattini ◽  
Iná Kakitani ◽  
Eduardo Massad ◽  
Almério de Castro Gomes

Populations of Anopheles (Kerteszia) were sampled fortnightly over a one-year period (August 1991 to July 1992) at Ribeira Valley, S. Paulo State, Brazil. Indoor and outdoor collections were made on human bait at evening crepuscular period. The Polovodova technique for age grading was applied to 3,501 females of Anopheles cruzii and to 416 females of An. bellator. That sample represented 34.4% of the total number of mosquitoes collected. The most abundant species found was An. cruzii. However, An. bellator showed an endophagy that was almost three times greater than that of An. cruzii. The overall parous rate was 25.4% and uniparity was practically dominant one. A proportion of 26.9% of An. cruzii and 12.0% of An. bellator were found to be uniparous. Only three outdoor females of the former species (0.1%) showed biparity. Parity of An. cruzii was higher in females caught outdoors than in those caught indoors. Nevertheless, 497 nulliparous females examined (417 cruzii and 80 bellator) had ovaries that had advanced to Christophers and Mer stages III to V. These results imply that these females had already practised hematophagy. Relating these results to those from the parous females, a high statistical significance was found, leading to the conclusion that gonothophic discordance is a common pattern among these anophelines. Further, these results obtained with human bait catches strongly suggest that nearly 38.0% of these host-seeking females had already taken at least one previous blood-meal. So it is possible that enough time could thus be available for the plasmodian development in the vectors.


2019 ◽  
Author(s):  
Miguel A. Vadillo

Ego depletion has been successfully replicated in hundreds of studies. Yet the most recent large-scale Registered Replication Reports (RRR), comprising thousands of participants, have yielded disappointingly small effects, sometimes even failing to reach statistical significance. Although these results may seem surprising, in the present article I suggest that they are perfectly consistent with a long-term decline in the size of the depletion effects that can be traced back to at least 10 years ago, well before any of the RRR on ego depletion were conceived. The decline seems to be at least partly due to a parallel trend toward publishing better and less biased research.


2016 ◽  
Vol 32 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Denis Kucevic ◽  
Snezana Trivunovic ◽  
Vladan Bogdanovic ◽  
Ksenija Cobanovic ◽  
Dobrila Jankovic ◽  
...  

Possible differences between composition of raw milk due to dairy farming system (organic vs conventional) as well as seasonal variations were investigated. The samples were analysed during one year. A total of 6.782 samples of raw milk were collected (4.496 from organic farming). Dairy farms were located in the northern part of Republic of Serbia (Province of Vojvodina). The principle of analysis of raw milk samples was in accordance with the methodology by midinfrared spectrometry and flow cytometry. The fixed effect of system of farming and season (winter, spring, summer and fall) have shown a high statistical significance (P < 0.01) on all examined milk parameters except fat, total solids and somatic cell count, where the impact was slightly lower (P < 0.05). Significant difference wasn't found in number of bacterial colonies (P > 0.05). Composition of milk is also affected by a number of other factors, therefore it is recommended to involve factors such as nutrition of dairy cows, breed and farm management.


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