scholarly journals A New Functional F-Statistic for Gene-Based Inference Involving Multiple Phenotypes

2021 ◽  
Author(s):  
Adam J. Dugan ◽  
David W. Fardo ◽  
Dmitri V. Zaykin ◽  
Olga A Vsevolozhskaya
Keyword(s):  
Single Gene ◽  
Small Sample ◽  
Multiple Traits ◽  
Genetic Pleiotropy ◽  
Multiple Phenotypes ◽  
Gene Level ◽  
Novel Associations ◽  
Better Than ◽  
Modest Effect ◽  
F Statistics

Genetic pleiotropy is the phenomenon where a single gene or genetic variant influences multiple traits. Numerous statistical methods exist for testing for genetic pleiotropy at the variant level, but fewer methods are available for testing genetic pleiotropy at the gene-level. In the current study, we derive an exact alternative to the Shen and Faraway functional F-statistic for functional-on-scalar regression models. Through extensive simulation studies, we show that this exact alternative performs similarly to the Shen and Faraway F-statistic in gene-based, multi-phenotype analyses and both F-statistics perform better than existing methods in small sample, modest effect size situations. We then apply all methods to real-world, neurodegenerative disease data and identify novel associations.

Cereal Consumption, Production, and Prices in West Pakistan (Notes & Comments)

1968 ◽  
Vol 8 (2) ◽  
pp. 288-306 ◽  
Author(s):  
G. C. Hufbauer
Keyword(s):  
Food Consumption ◽  
Ad Hoc ◽  
Dry Weight ◽  
Small Sample ◽  
Tax Rates ◽  
Active Population ◽  
Early Settlement ◽  
Consumption Rates ◽  
Late Nineteenth ◽  
Better Than

In the late nineteenth and early twentieth centuries, several Punjab Settlement Officers attempted to estimate food consumption rates. These estimates, based on direct observation and ad hoc guesses, were made partly out of academic curiosity, but more urgently, as an aid in establishing the land revenue (i.e., tax) rates. The pre-1926 estimates are summarized in Table I, expressed in pounds of wheat and other foodgrain consumption per person per year1. Broadly speaking, the later, more systemtic observers (e.g., Sir Ganga Ram and C. B. Barry), found lower consumption levels than the earlier observers. It was generally accepted that the rural populace ate better than urban dwellers. Despite the ingenuity of the early Settlement Officers, their compiled estimates suffer from all the difficulties of haphazard small sample observation. Given the revenue purpose of the estimates, they may be biased towards the able-bodied, economically active, population. Further, the very early estimates may have confused dry weight with cooked weight, including water.

Modules in Biological Networks

2013 ◽  
pp. 637-663
Author(s):  
Bing Zhang ◽  
Zhiao Shi
Keyword(s):  
Biological Networks ◽  
Protein Complex ◽  
Protein Function ◽  
Protein Function Prediction ◽  
Single Gene ◽  
Biological Systems ◽  
Function Prediction ◽  
Diverse Group ◽  
Biological Studies ◽  
Gene Level

One of the most prominent properties of networks representing complex systems is modularity. Network-based module identification has captured the attention of a diverse group of scientists from various domains and a variety of methods have been developed. The ability to decompose complex biological systems into modules allows the use of modules rather than individual genes as units in biological studies. A modular view is shaping research methods in biology. Module-based approaches have found broad applications in protein complex identification, protein function prediction, protein expression prediction, as well as disease studies. Compared to single gene-level analyses, module-level analyses offer higher robustness and sensitivity. More importantly, module-level analyses can lead to a better understanding of the design and organization of complex biological systems.

Bayesian jackknife empirical likelihood

Biometrika ◽  
2019 ◽  
Vol 106 (4) ◽  
pp. 981-988
Author(s):  
Y Cheng ◽  
Y Zhao
Keyword(s):  
Bayesian Inference ◽  
Empirical Likelihood ◽  
Small Sample ◽  
New Approach ◽  
U Statistics ◽  
Posterior Inference ◽  
Jackknife Empirical Likelihood ◽  
General Tool ◽  
Control Study ◽  
Better Than

Summary Empirical likelihood is a very powerful nonparametric tool that does not require any distributional assumptions. Lazar (2003) showed that in Bayesian inference, if one replaces the usual likelihood with the empirical likelihood, then posterior inference is still valid when the functional of interest is a smooth function of the posterior mean. However, it is not clear whether similar conclusions can be obtained for parameters defined in terms of $U$-statistics. We propose the so-called Bayesian jackknife empirical likelihood, which replaces the likelihood component with the jackknife empirical likelihood. We show, both theoretically and empirically, the validity of the proposed method as a general tool for Bayesian inference. Empirical analysis shows that the small-sample performance of the proposed method is better than its frequentist counterpart. Analysis of a case-control study for pancreatic cancer is used to illustrate the new approach.

The Model of Pump Head Data Mining Based on SVM

2013 ◽  
Vol 405-408 ◽  
pp. 3263-3268
Author(s):  
Kai Ding ◽  
Jin Hui Zhang ◽  
Xiao Xun Zhu
Keyword(s):  
Data Mining ◽  
Measured Data ◽  
Small Sample ◽  
Support Vector ◽  
Water Pump ◽  
Pump Performance ◽  
Real Condition ◽  
Pump Head ◽  
Flow Head ◽  
Better Than

The curve of flow-head is one of the most important indicators to assess water pump performance. While it is difficult to get measured data in real condition and the data is very limited. The method of pump data mining based on support vector machine (SVM) is built due to its superiority in dealing with small sample event. The method is aimed at finding out the unknown data between measured data and drawing more accurate flow-head curve. It was found that the model of pump data mining based on SVM is much better than neural network when their curves are compared.

scholarly journals Gene-level quantitative trait mapping in an expandedC. elegansmultiparent experimental evolution panel

2019 ◽  
Author(s):  
Luke M. Noble ◽  
Matthew V. Rockman ◽  
Henrique Teotónio
Keyword(s):  
Experimental Evolution ◽  
Recombinant Inbred Lines ◽  
Single Gene ◽  
Ancestral Population ◽  
C Elegans ◽  
Quantitative Trait Mapping ◽  
Trait Variance ◽  
Gene Level ◽  
Evolution Experiment

ABSTRACTTheCaenorhabditis elegansmultiparental experimental evolution (CeMEE) panel is a collection of genome-sequenced, cryopreserved recombinant inbred lines useful for mapping the genetic basis and evolution of quantitative traits. We have expanded the resource with new lines and new populations, and here report updated additive and epistatic mapping simulations and the genetic and haplotypic composition of CeMEE version 2. Additive QTL explaining 3% of trait variance are detected with >80% power, and the median detection interval is around the length of a single gene on the highly recombinant chromosome arms. Although CeMEE populations are derived from a long-term evolution experiment, genetic structure is dominated by variation present in the ancestral population and is not obviously associated with phenotypic differentiation.C. elegansprovides exceptional experimental advantages for the study of phenotypic evolution.

scholarly journals The impact of incongruence and exogenous gene fragments on estimates of the eukaryote root

2021 ◽  
Author(s):  
Caesar Al Jewari ◽  
Sandra L Baldauf
Keyword(s):  
Phylogenetic Analyses ◽  
Single Gene ◽  
Evolutionary Model ◽  
Bootstrap Support ◽  
Gene Trees ◽  
Full Data ◽  
Data Set ◽  
Gene Level ◽  
The Impact ◽  
Exogenous Gene

Phylogenomics uses multiple genetic loci to reconstruct evolutionary trees, under the stipulation that all combined loci share a common phylogenetic history, i.e., they are congruent. Congruence is primarily evaluated via single-gene trees, but these trees invariably lack sufficient signal to resolve deep nodes making it difficult to assess congruence at these levels. Two methods were developed to systematically assess congruence in multi-locus data. Protocol 1 uses gene jackknifing to measure deviation from a central mean to identify taxon-specific incongruencies in the form of persistent outliers. Protocol_2 assesses congruence at the sub-gene level using a sliding window. Both protocols were tested on a controversial data set of 76 mitochondrial proteins previously used in various combinations to assess the eukaryote root. Protocol_1 showed a concentration of outliers in under-sampled taxa, including the pivotal taxon Discoba. Further analysis of Discoba using Protocol_2 detected a surprising number of apparently exogenous gene fragments, some of which overlap with Protocol_1 outliers and others that do not. Phylogenetic analyses of the full data using the static LG-gamma evolutionary model support a neozoan-excavate root for eukaryotes (Discoba sister), which rises to 99-100% bootstrap support with data masked according to either Protocol_1 or Protocol_2. In contrast, site-heterogeneous (mixture) models perform inconsistently with these data, yielding all three possible roots depending on presence/absence/type of masking and/or extent of missing data. The neozoan-excavate root places Amorphea (including animals and fungi) and Diaphoretickes (including plants) as more closely related to each other than either is to Discoba (Jakobida, Heterolobosea, and Euglenozoa), regardless of the presence/absence of additional taxa.

scholarly journals Enrichment of SARM1 alleles encoding variants with constitutively hyperactive NADase in patients with ALS and other motor nerve disorders

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jonathan Gilley ◽  
Oscar Jackson ◽  
Menelaos Pipis ◽  
Mehrdad A Estiar ◽  
Ammar Al-Chalabi ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Neuronal Degeneration ◽  
Motor Nerve ◽  
Single Gene ◽  
Patient Specific ◽  
Mild Stress ◽  
Nicotinamide Mononucleotide ◽  
Genome Wide ◽  
Gene Level ◽  
Coding Variants

SARM1, a protein with critical NADase activity, is a central executioner in a conserved programme of axon degeneration. We report seven rare missense or in-frame microdeletion human SARM1 variant alleles in patients with amyotrophic lateral sclerosis (ALS) or other motor nerve disorders that alter the SARM1 auto-inhibitory ARM domain and constitutively hyperactivate SARM1 NADase activity. The constitutive NADase activity of these seven variants is similar to that of SARM1 lacking the entire ARM domain and greatly exceeds the activity of wild-type SARM1, even in the presence of nicotinamide mononucleotide (NMN), its physiological activator. This rise in constitutive activity alone is enough to promote neuronal degeneration in response to otherwise non-harmful, mild stress. Importantly, these strong gain-of-function alleles are completely patient-specific in the cohorts studied and show a highly significant association with disease at the single gene level. These findings of disease-associated coding variants that alter SARM1 function build on previously reported genome-wide significant association with ALS for a neighbouring, more common SARM1 intragenic single nucleotide polymorphism (SNP) to support a contributory role of SARM1 in these disorders. A broad phenotypic heterogeneity and variable age-of-onset of disease among patients with these alleles also raises intriguing questions about the pathogenic mechanism of hyperactive SARM1 variants.

scholarly journals Physical activity and blood gene expression profiles: the Norwegian Women and Cancer (NOWAC) Post-genome cohort

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Karina Standahl Olsen ◽  
Marko Lukic ◽  
Kristin Benjaminsen Borch
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Expression Profiles ◽  
Single Gene ◽  
Gene Expression Profiles ◽  
R Package ◽  
Middle Aged ◽  
Blood Gene Expression ◽  
Gene Sets ◽  
Gene Level

Abstract Objectives The influence of physical activity (PA) on the immune system has emerged as a new field of research. Regular PA may promote an anti-inflammatory state in the body, thus contributing to the down-regulation of pro-inflammatory processes related to the onset and progression of multiple diseases. We aimed to assess whether overall PA levels were associated with differences in blood gene expression profiles, in a cohort of middle-aged Norwegian women. We used information from 977 women included in the Norwegian Women and Cancer (NOWAC) Post-genome cohort. Information on PA and covariates was extracted from the NOWAC database. Blood samples were collected using the PAXgene Blood RNA collection system, and gene expression profiles were measured using Illumina microarrays. The R-package limma was used for the single-gene level analysis. For a target gene set analysis, we used the global test R-package with 48 gene sets, manually curated from the literature and relevant molecular databases. Results We found no associations between overall PA levels and gene expression profiles at the single-gene level. Similarly, no gene sets reached statistical significance at adjusted p < 0.05. In our analysis of healthy, middle-aged Norwegian women, self-reported overall PA was not associated with differences in blood gene expression profiles.

scholarly journals Characterization of Single Gene Deletion Mutants Affecting Alternative Oxidase Production in Neurospora crassa: Role of the yvh1 Gene

2020 ◽  
Vol 8 (8) ◽  
pp. 1186
Author(s):  
Adrien Beau Desaulniers ◽  
Nishka Kishore ◽  
Kelly Adames ◽  
Frank E. Nargang
Keyword(s):  
Neurospora Crassa ◽  
Gene Deletion ◽  
Alternative Oxidase ◽  
Single Gene ◽  
Ribosome Assembly ◽  
Mitochondrial Translation ◽  
Multiple Phenotypes ◽  
Transport Chain ◽  
Zinc Binding Domain ◽  
Single Gene Deletion

The Neurospora crassa AOD1 protein is a mitochondrial alternative oxidase that passes electrons directly from ubiquinol to oxygen. The enzyme is encoded by the nuclear aod-1 gene and is produced when the standard electron transport chain is inhibited. We previously identified eleven strains in the N. crassa single gene deletion library that were severely deficient in their ability to produce AOD1 when grown in the presence of chloramphenicol, an inhibitor of mitochondrial translation that is known to induce the enzyme. Three mutants affected previously characterized genes. In this report we examined the remaining mutants and found that the deficiency of AOD1 was due to secondary mutations in all but two of the strains. One of the authentic mutants contained a deletion of the yvh1 gene and was found to have a deficiency of aod-1 transcripts. The YVH1 protein localized to the nucleus and a post mitochondrial pellet from the cytoplasm. A zinc binding domain in the protein was required for rescue of the AOD1 deficiency. In other organisms YVH1 is required for ribosome assembly and mutants have multiple phenotypes. Lack of YVH1 in N. crassa likely also affects ribosome assembly leading to phenotypes that include altered regulation of AOD1 production.

Psychoacoustic and Demographic Factors for Speech Recognition of Older Adult Cochlear Implant Users

2020 ◽  
Vol 63 (6) ◽  
pp. 1712-1725
Author(s):  
Xin Luo ◽  
Courtney Kolberg ◽  
Kathryn R. Pulling ◽  
Tamiko Azuma
Keyword(s):  
Speech Recognition ◽  
Cochlear Implant ◽  
Discrimination Performance ◽  
Demographic Factors ◽  
Small Sample ◽  
Gap Detection ◽  
Sentence Recognition ◽  
Speech Reception Thresholds ◽  
Effects Of Aging ◽  
Better Than

Purpose This study aimed to evaluate the effects of aging and cochlear implant (CI) on psychoacoustic and speech recognition abilities and to assess the relative contributions of psychoacoustic and demographic factors to speech recognition of older CI (OCI) users. Method Twelve OCI users, 12 older acoustic-hearing (OAH) listeners age-matched to OCI users, and 12 younger normal-hearing (YNH) listeners underwent tests of temporal amplitude modulation detection, temporal gap detection in noise, and spectral–temporal modulated ripple discrimination. Speech reception thresholds were measured for sentence recognition in multitalker, speech-babble noise. Results Statistical analyses showed that, for the small sample of OAH listeners, the degree of hearing loss did not significantly affect any outcome measure. Temporal resolution, spectral resolution, and speech recognition all significantly degraded with both age and the use of a CI (i.e., YNH better than OAH and OAH better than OCI performance). Although both were significantly correlated with OCI users' speech recognition, the duration of CI use no longer had a significant effect on speech recognition once the effect of spectral–temporal ripple discrimination performance was taken into account. For OAH listeners, the only significant predictor of speech recognition was temporal gap detection performance. Conclusion The preliminary results suggest that speech recognition of OCI users may improve with longer duration of CI use, mainly due to higher perceptual acuity to spectral–temporal modulated ripples in acoustic stimuli.

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