Relative Distribution Methods in the Social Sciences

Handcock, Mark S.; Morris, Martina

doi:10.1007/b97852

Cited by 42 publications

(4 citation statements)

References 101 publications

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“…However, all these measures provide a single effect size estimate that may not be very informative or could even be misleading with regard to the possible complex differences between two distributions 23,35,36 . To fully represent and compare distributions, robust statistical and informatively-rich graphical methods such as the cumulative distribution function (CDF) 25 and the shiftfunction 23,24 are required 23,25,[36][37][38][39] . Consequently, we used these methods to provide two complementary perspectives 23 of the multivariate sex differences in GMVOL.…”

Section: Resultsmentioning

confidence: 99%

“…Because no single score can properly summarize the differences between two distributions 23,25,[35][36][37][38][39] , male-female differences in the PCAM continuum were characterized by comparing their cumulative distribution functions (CDF; 25,35 ). CDFs make it possible to directly estimate the proportion of cases in each group with PCAM values equal to or lower than any possible cutoff, but also the proportion of subjects in one group have PCAM values equal or lower than a given proportion of cases in another group 25,35 .…”

Section: Statistical Analysesmentioning

confidence: 99%

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Beyond “Sex Prediction”: Estimating and Interpreting Multivariate Sex Differences and Similarities in the Brain

Sanchis-Segura

Aguirre

Cruz-Gómez

et al. 2022

Preprint

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Previous studies have shown that machine-learning (ML) algorithms can “predict” sex based on brain anatomical/ functional features. The high classification accuracy achieved by ML algorithms is often interpreted as revealing large differences between the brains of males and females and as confirming the existence of “male/female brains”. However, classification and estimation are quite different concepts, and using classification metrics as surrogate estimates of between-group differences results in major statistical and interpretative distortions. The present study illustrates these distortions and provides a novel and detailed assessment of multivariate sex differences in gray matter volume (GMVOL) that does not rely on classification metrics. Moreover, modeling and clustering techniques and analyses of similarities (ANOSIM) were used to identify the brain areas that contribute the most to these multivariate differences, and to empirically assess whether they assemble into two sex-typical profiles. Results revealed that multivariate sex differences in GMVOL: 1) are “large” if not adjusted for total intracranial volume (TIV) variation, but “small” when controlling for this variable; 2) differ in size between individuals and also depends on the ML algorithm used for their calculation 3) do not stem from two sex-typical profiles, and so describing them in terms of “male/female brains” is misleading.

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Section: Resultsmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

Beyond “Sex Prediction”: Estimating and Interpreting Multivariate Sex Differences and Similarities in the Brain

Sanchis-Segura

Aguirre

Cruz-Gómez

et al. 2022

Preprint

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“…Cells were then clustered under a graph-based approach by first identifying K-nearest neighbors in PCA space, and then clustering under a Louvain algorithm with a resolution of 0.1. Gini coefficients were calculated using the gini() function that is available in the reldist v1.6-6 package 127,128 using RNA expression values obtained with the Seurat function AverageExpression(). Differential gene expression testing was performed using DESeq2 v.1.40.2 122 with a likelihood-ratio test to identify distinct genes among the D1-MSN clusters.…”

Section: Methodsmentioning

confidence: 99%

Reelin marks cocaine-activated striatal ensembles, promotes neuronal excitability, and regulates cocaine reward

Brida,

Jorgensen,

Phillips

et al. 2024

Preprint

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SummaryDrugs of abuse activate defined neuronal ensembles in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, the mechanisms that sculpt NAc ensemble participation are largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling to identify expression of the secreted glycoprotein Reelin (encoded by theRelngene) as a marker of cocaine-activated neuronal ensembles within the rat NAc. Multiplexed in situ detection confirmed selective expression of the immediate early geneFosinReln+neurons after cocaine experience, and also revealed enrichment ofRelnmRNA inDrd1+ medium spiny neurons (MSNs) in both the rat and human brain. Using a novel CRISPR interference strategy enabling selectiveRelnknockdown in the adult NAc, we observed altered expression of genes linked to calcium signaling, emergence of a transcriptional trajectory consistent with loss of cocaine sensitivity, and a striking decrease in MSN intrinsic excitability. At the behavioral level, loss ofRelnprevented cocaine locomotor sensitization, abolished cocaine place preference memory, and decreased cocaine self-administration behavior. Together, these results identify Reelin as a critical mechanistic link between ensemble participation and cocaine-induced behavioral adaptations.

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“…Resulting p -values were adjusted using the Bonferroni correction based on the number of genes identified in each cluster. Gini coefficients were calculated using the average log23-normalized gene expression values for each cluster with the gini() command from the reldist R package 87,88 . All R code is available at https://gitlab.rc.uab.edu/day-lab.…”

Section: Methodsmentioning

confidence: 99%

An atlas of transcriptionally defined cell populations in the rat ventral tegmental area

Tuscher

et al. 2021

Preprint

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The ventral tegmental area (VTA) is a complex brain region that is essential for reward function but is also implicated in neuropsychiatric diseases including substance abuse. While decades of research on VTA function have focused on the role of dopaminergic neurons, recent evidence has identified critical roles for VTA GABAergic and glutamatergic neurons in reward processes as well. Interestingly, molecular characterization has revealed that subsets of these neurons express genes involved in the transport, synthesis, and vesicular packaging of multiple neurotransmitters, providing evidence for co-release neurons. However, these studies have largely relied on low-throughput methods, and the molecular architecture of the VTA has not been comprehensively examined. Here, we performed single nucleus RNA-sequencing (snRNA-seq) on 21,600 VTA cells from male and female Sprague-Dawley rats to generate a transcriptional atlas of the rat VTA. We identified 16 transcriptionally distinct cell types within the VTA, including 7 neuronal populations. Further subclustering revealed several VTA neuronal populations expressing markers for more than one neurotransmitter system, with one cluster exhibiting high expression levels of genes involved in the synthesis and transport of GABA, glutamate, and dopamine. Finally, snRNA-seq enabled the de novo identification of thousands of marker genes for each transcriptionally distinct population, revealing cluster-specific enrichment of gene sets implicated in neuropsychiatric and neurodevelopmental disorders, as well as specific phenotypes associated with alcohol and tobacco use. Together, these results highlight the heterogeneity of cellular populations in the VTA and identify novel markers and disease-linked genes enriched in distinct neuronal subtypes.

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Relative Distribution Methods in the Social Sciences

Cited by 42 publications

References 101 publications

Beyond “Sex Prediction”: Estimating and Interpreting Multivariate Sex Differences and Similarities in the Brain

Beyond “Sex Prediction”: Estimating and Interpreting Multivariate Sex Differences and Similarities in the Brain

Reelin marks cocaine-activated striatal ensembles, promotes neuronal excitability, and regulates cocaine reward

An atlas of transcriptionally defined cell populations in the rat ventral tegmental area

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