A novel significance score for gene selection and ranking

Xiao, Yufei; Hsiao, Tzu Hung; Suresh, Uthra; Chen, Hung I Harry; Wu, Xiaowu; Wolf, Steven E.; Chen, Yidong

doi:10.1093/bioinformatics/btr671

Cited by 243 publications

(256 citation statements)

References 23 publications

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“…Gene expression analysis was performed by the multifactor model of the R package for differential expression analysis for sequence count data (51). Effects of humanized Foxp2 were summarized by the π-value that multiplies the magnitude and significance of genotype effect (52). This ranking was used for the Wilcoxon rank test implemented in FUNC (https://func.eva.mpg.de/) (53) to identify enriched Gene Ontology categories.…”

Section: Methodsmentioning

confidence: 99%

Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance

Schreiweis

Bornschein

Burguière

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

162

136

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The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into the endogenous Foxp2 gene of mice (Foxp2 hum ), cortico-basal ganglia circuits are specifically affected. Here we demonstrate marked effects of this humanization of Foxp2 on learning and striatal neuroplasticity. Foxp2 hum/hum mice learn stimulus-response associations faster than their WT littermates in situations in which declarative (i.e., place-based) and procedural (i.e., response-based) forms of learning could compete during transitions toward proceduralization of action sequences. Striatal districts known to be differently related to these two modes of learning are affected differently in the Foxp2 hum/hum mice, as judged by measures of dopamine levels, gene expression patterns, and synaptic plasticity, including an NMDA receptor-dependent form of long-term depression. These findings raise the possibility that the humanized Foxp2 phenotype reflects a different tuning of corticostriatal systems involved in declarative and procedural learning, a capacity potentially contributing to adapting the human brain for speech and language acquisition.T he gene encoding the transcription factor forkhead box P2 (FOXP2) is a promising candidate for investigating the evolutionary basis of human speech and language capabilities. Humans carrying only one functional copy of this transcription factor experience difficulties in learning and performing complex orofacial movements and have receptive and expressive deficits in oral and written language, whereas other cognitive skills are less affected. These speech and language deficits are associated with functional impairments in cortico-basal ganglia and corticocerebellar circuits (1). Since the time that the human and chimpanzee lineages separated, approximately 6 Mya, two amino acid substitutions have occurred in FOXP2, a higher rate of change than expected given its conservation in mammals (2, 3). Mice in which the endogenous Foxp2 gene has been "humanized" for these two amino acid changes (Foxp2 hum/hum mice) exhibit prominent neurochemical, neurophysiological, and neuroanatomical alterations in the striatum and related cortico-basal ganglia circuits (4, 5). These circuits are known to be essential for acquiring habits and other motor and cognitive behaviors (6), including vocal learning in songbirds (7) and speech and language capabilities in humans (8). However, whether learning behavior depending on these circuits is affected in Foxp2 hum/hum mice has so far not been investigated.A key functional distinction has been made between subregions of the striatum that underlie modes o...

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Section: Methodsmentioning

confidence: 99%

Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance

Schreiweis

Bornschein

Burguière

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

162

136

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“…Pathway analysis involving genes important in dairy cattle production was a part of the study by Cochran et al (2013). Xiao et al (2014) used the real data set to generate background data for hypothesis testing, which is conceptually similar to our approach; however, it was based on data resampling, not on permutation. In agreement with our study, but in the context of gene expression analysis, Zhe et al (2013) and Verbanck et al (2013) indicate that the incorporation of pathway information, which represents biologically functional groups of genes, improves interpretability of results.…”

Section: Discussionmentioning

confidence: 99%

Using gene networks to identify genes and pathways involved in milk production traits in Polish Holstein dairy cattle

Suchocki¹,

Wojdak-Maksymiec²,

Szyda³

2016

CZECH J ANIM SCI

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ABSTRACT:When analyzing phenotypes undergoing a complex mode of inheritance, it is of great interest to switch the scope from single genes to gene pathways, which form better defined functional units. We used gene networks to search for physiological processes and underlying genes responsible for complex traits recorded in dairy cattle. Major problems addressed included loss of information from multiple single nucleotide polymorphisms (SNPs) located within or close to the same gene, ignoring information on linkage disequilibrium and validation of the obtained gene network. 2601 bulls genotyped by the Illumina BovineSNP50 BeadChip were used. SNP effects were estimated using a mixed model, then underlying gene effects were estimated and tested for significance, subsequently a gene network was constructed and the functional information represented by the network was retrieved. The networks were validated by repeating the above-mentioned analyses after permutation of bulls' pseudophenotypes. Effects of 4345 genes were estimated, what makes 16.4% of all genes mapped to the UMD3.1 reference genome. Assuming the maximum 10% type I error rate, for milk yield 50 different gene ontology (GO) terms and three pathways defined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) were significantly overrepresented in the real data as compared to the permuted data sets, while for fat yield nine of the GO terms were significantly overrepresented in the real data network, although none of the KEGG pathways reached the significance level. In turn, for protein yield 28 of the GO terms and six KEGG pathways were significantly overrepresented in the real data. Based on the physiological information we identified sets of loci involved in the determination of milk yield (224 genes), fat yield (72 genes), and protein yield (546 genes). Among the genes some have large effects and have already been reported in previous studies, whereas some others represent novel discoveries and thus most probably genes with medium or small effects on trait variation.

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“…70; P < 0.05 for significant DEGs); and (c) average intensity from at least 1 group of greater than 4 (log 2 ). Additional P values for other differential gene expression assessments were also obtained, including rank-sum test and pi value, a unique statistic that combines the t test's P value and fold change (71). Multi-dimensional scaling (MDS) was performed by applying a MDS algorithm to the gene expression data to visualize the relationship (Pearson coefficient) between samples (72).…”

Section: Methodsmentioning

confidence: 99%

Hepatoblastoma modeling in mice places Nrf2 within a cancer field established by mutant β-catenin

Comerford¹,

Hinnant²,

Chen³

et al. 2016

JCI Insight

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A novel significance score for gene selection and ranking

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 243 publications

References 23 publications

Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance

Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance

Using gene networks to identify genes and pathways involved in milk production traits in Polish Holstein dairy cattle

Hepatoblastoma modeling in mice places Nrf2 within a cancer field established by mutant β-catenin

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