Two different nuclear-medium effects are isolated using a low three-momentum transfer subsample of neutrino-carbon scattering data from the MINERvA neutrino experiment. The observed hadronic energy ...in charged-current ν_{μ} interactions is combined with muon kinematics to permit separation of the quasielastic and Δ(1232) resonance processes. First, we observe a small cross section at very low energy transfer that matches the expected screening effect of long-range nucleon correlations. Second, additions to the event rate in the kinematic region between the quasielastic and Δ resonance processes are needed to describe the data. The data in this kinematic region also have an enhanced population of multiproton final states. Contributions predicted for scattering from a nucleon pair have both properties; the model tested in this analysis is a significant improvement but does not fully describe the data. We present the results as a double-differential cross section to enable further investigation of nuclear models. Improved description of the effects of the nuclear environment are required by current and future neutrino oscillation experiments.
Charged-current antineutrino interactions on a hydrocarbon scintillator in the MINERvA detector are used to study activity from their final-state neutrons. To ensure that most of the neutrons are ...from the primary interaction, rather than hadronic reinteractions in the detector, the sample is limited to momentum transfers below 0.8 GeV/c. From 16 129 interactions, 15 246 neutral particle candidates are observed. The reference simulation predicts 64% of these candidates are due to neutrons from the antineutrino interaction directly but also overpredicts the number of candidates by 15% overall. This discrepancy is beyond the standard uncertainty estimates for models of neutrino interactions and neutron propagation in the detector. We explore these two aspects of the models using the measured distributions for energy deposition, time of flight, position, and speed. We also use multiplicity distributions to evaluate the presence of a two-nucleon knockout process. These results provide critical new information toward a complete description of the hadronic final state of neutrino interactions, which is vital to neutrino oscillation experiments.
Single-cell sequencing technologies that simultaneously generate multimodal cellular profiles present opportunities for improved understanding of cell heterogeneity in tissues. How the multimodal ...information can be integrated to obtain a common cell type identification, however, poses a computational challenge. Multilayer graphs provide a natural representation of multi-omic single-cell sequencing datasets, and finding cell clusters may be understood as a multilayer graph partition problem.
We introduce two spectral algorithms on multilayer graphs, spectral clustering on multilayer graphs and the weighted locally linear (WLL) method, to cluster cells in multi-omic single-cell sequencing datasets. We connect these algorithms through a unifying mathematical framework that represents each layer using a Hamiltonian operator and a mixture of its eigenstates to integrate the multiple graph layers, demonstrating in the process that the WLL method is a rigorous multilayer spectral graph theoretic reformulation of the popular Seurat weighted nearest neighbor (WNN) algorithm. Implementing our algorithms and applying them to a CITE-seq dataset of cord blood mononuclear cells yields results similar to the Seurat WNN analysis. Our work thus extends spectral methods to multimodal single-cell data analysis.
The code used in this study can be found at https://github.com/jssong-lab/sc-spectrum. All public data used in the article are accurately cited and described in Materials and Methods and in Supplementary Information.
Supplementary data are available at Bioinformatics online.
Understanding the epigenomic evolution and specificity of disease subtypes from complex patient data remains a major biomedical problem. We here present DeCET (decomposition and classification of ...epigenomic tensors), an integrative computational approach for simultaneously analyzing hierarchical heterogeneous data, to identify robust epigenomic differences among tissue types, differentiation states, and disease subtypes. Applying DeCET to our own data from 21 uterine benign tumor (leiomyoma) patients identifies distinct epigenomic features discriminating normal myometrium and leiomyoma subtypes. Leiomyomas possess preponderant alterations in distal enhancers and long-range histone modifications confined to chromatin contact domains that constrain the evolution of pathological epigenomes. Moreover, we demonstrate the power and advantage of DeCET on multiple publicly available epigenomic datasets representing different cancers and cellular states. Epigenomic features extracted by DeCET can thus help improve our understanding of disease states, cellular development, and differentiation, thereby facilitating future therapeutic, diagnostic, and prognostic strategies.
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•Tensor decomposition provides integrative analysis of epigenomic data•Leiomyomas exhibit recurrent subtype-specific alterations in histone modifications•Chromatin contact domains constrain histone modification alterations in leiomyoma•HOXA13 is a potential tumorigenic factor in leiomyoma
Leistico et al. apply tensor decomposition and classification methods to integrate information from hierarchical heterogenous epigenomic datasets and identify histone modification patterns that discriminate disease conditions, tissue types, and differentiation states. Leiomyomas are shown to possess alterations in distal enhancers and large-scale regions confined to chromatin contact domains.
Psychopathy has been conceptualized as a personality disorder with distinctive interpersonal-affective and behavioral deviance features. The authors examine correlates of the factors of the ...Psychopathic Personality Inventory (PPI), Self-Report Psychopathy-II (SRP-II) scale, and Antisocial Process Screening Device (APSD) to understand similarities and differences among the constructs embodied in these instruments. PPI Fearless Dominance and SRP-II Factor 1 were negatively related to most personality disorder symptoms and were both predicted by high Dominance and low Neuroticism. In addition, PPI Fearless Dominance correlated positively with antisocial personality features, although SRP-II Factor 1 did not. In contrast, PPI Impulsive Antisociality, SRP-II Factor 2, and both APSD factors correlated with antisocial personality features and symptoms of nearly all personality disorders, and were predicted by low Love. Results suggest ways in which the measurement of the constructs in each instrument may be improved.
Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA ...sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45+ subpopulations, which broadly represent most functionally characterized immune cell types. Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and antigen-presenting cells (APCs). Oxazolone also induces Il4/Il13 expression in newly infiltrating basophils, and Il4ra and Ccl24, most prominently in APCs. In contrast, imiquimod broadly upregulates Il17/Il22 and Ccl4/Ccl5. A comparative analysis of single-cell inflammatory transcriptional responses reveals that APC response to oxazolone is tightly restricted by cell identity, whereas imiquimod enforces shared programs on multiple APC populations in parallel. These global molecular patterns not only contrast immune responses on a systems level but also suggest that the mechanisms of new sources of inflammation can eventually be deduced by comparison to known signatures.
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•Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and APCs•Il4/Il13 induction in skin by oxazolone is dominated by infiltrating basophils•Imiquimod broadly increases Il17/Il22 and Ccl4/Ccl5, extending to non-T cells•Oxazolone induces more highly compartmentalized immune cell responses than imiquimod
Immunology; Systems Biology
Recent advances in next generation sequencing-based single-cell technologies have allowed high-throughput quantitative detection of cell-surface proteins along with the transcriptome in individual ...cells, extending our understanding of the heterogeneity of cell populations in diverse tissues that are in different diseased states or under different experimental conditions. Count data of surface proteins from the cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) technology pose new computational challenges, and there is currently a dearth of rigorous mathematical tools for analyzing the data. This work utilizes concepts and ideas from Riemannian geometry to remove batch effects between samples and develops a statistical framework for distinguishing positive signals from background noise. The strengths of these approaches are demonstrated on two independent CITE-seq data sets in mouse and human.
We report on multinucleon effects in low momentum transfer (\(< 0.8\) GeV/c) anti-neutrino interactions on plastic (CH) scintillator. These data are from the 2010-2011 antineutrino phase of the ...MINERvA experiment at Fermilab. The hadronic energy spectrum of this inclusive sample is well described when a screening effect at low energy transfer and a two-nucleon knockout process are added to a relativistic Fermi gas model of quasielastic, \(\Delta\) resonance, and higher resonance processes. In this analysis, model elements introduced to describe previously published neutrino results have quantitatively similar benefits for this antineutrino sample. We present the results as a double-differential cross section to accelerate investigation of alternate models for antineutrino scattering off nuclei.
The construct validity of psychopathy was examined in a sample of 114 male and female young offenders (M.sub.age = 15.16) at a southeastern detention center. The interpersonal circumplex served as a ...framework of general personality from which to examine the construct of adolescent psychopathy. A supplementary analysis of the psychopathy measures and the Big 5 factors of personality was also conducted using a matrix approach. Measures included: (a) Antisocial Process Screening Device (P. J. Frick & R. D. Hare, 2001); (b) Child Psychopathy Scale (D. R. Lynam, 1996); (c) Psychopathy Checklist--Youth Version (A. E. Forth, D. S. Kosson, & R. D. Hare, 2003); and (d) Interpersonal Adjective Scales Revised--Big 5 Version (P. Trapnell & J. S. Wiggins, 1991; J. S. Wiggins, 1995). Results showed substantial convergence among the three psychopathy measures. In addition, meaningful associations between psychopathy and constructs within the interpersonal circumplex and broader domains of the Big 5 were obtained. Two psychopathy scales correlated to a higher degree than expected with neuroticism. These findings provide evidence linking personality theory to the concept of child and adolescent psychopathy, thereby adding to its construct validity. However, they do so with the caveat that youth may also be displaying some characteristics of neuroticism, suggesting that worry and anxiety may accompany psychopathic features in earlier developmental stages. The implications of the current study are discussed. (Contains 7 notes.)
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