Brain Gene Expression Analysis: a MATLAB toolbox for the analysis of brain-wide gene-expression data

The Allen Brain Atlas project (ABA) generated a genome-scale collection of gene-expression profiles using in-situ hybridization. These profiles were co-registered to the three-dimensional Allen Reference Atlas (ARA) of the adult mouse brain. A set of more than 4,000 such volumetric data are available for the full brain, at a resolution of 200 microns. These data are presented in a voxel-by-gene matrix. The ARA comes with several systems of annotation, hierarchical (40 cortical regions, 209 sub-cortical regions in the whole brain), or non-hierarchical (12 regions in the left hemisphere, with refinement into 94 regions, and cortical layers). The high-dimensional nature of this unique dataset and the possible connection between anatomy and gene expression pose challenges to data analysis. We developed the Brain Gene Expression Analysis Toolbox (downloadable at: www.brainarchitecture.org). The key functionalities include: determination of marker genes for brain regions, statistical analysis of brain-wide co-expression patterns, and the computation of brain-wide correlation maps with cell-type specific microarray data. The auxiliary dataset consisting of cell-type-specific transcriptomes (chapter 4) will be made available in the second version of the toolbox

An analysis of the abstracts presented at the annual meetings of the Society for Neuroscience from 2001 to 2006

Annual meeting abstracts published by scientific societies often contain rich arrays of information that can be computationally mined and distilled to elucidate the state and dynamics of the subject field. We extracted and processed abstract data from the Society for Neuroscience (SFN) annual meeting abstracts during the period 2001-2006 in order to gain an objective view of contemporary neuroscience. An important first step in the process was the application of data cleaning and disambiguation methods to construct a unified database, since the data were too noisy to be of full utility in the raw form initially available. Using natural language processing, text mining, and other data analysis techniques, we then examined the demographics and structure of the scientific collaboration network, the dynamics of the field over time, major research trends, and the structure of the sources of research funding. Some interesting findings include a high geographical concentration of neuroscience research in the north eastern United States, a surprisingly large transient population (66% of the authors appear in only one out of the six studied years), the central role played by the study of neurodegenerative disorders in the neuroscience community, and an apparent growth of behavioral/systems neuroscience with a corresponding shrinkage of cellular/molecular neuroscience over the six year period. The results from this work will prove useful for scientists, policy makers, and funding agencies seeking to gain a complete and unbiased picture of the community structure and body of knowledge encapsulated by a specific scientific domain

Cell-type-based model explaining coexpression patterns of genes in the brain

Spatial patterns of gene expression in the vertebrate brain are not independent, as pairs of genes can exhibit complex patterns of coexpression. Two genes may be similarly expressed in one region, but differentially expressed in other regions. These correlations have been studied quantitatively, particularly for the Allen Atlas of the adult mouse brain, but their biological meaning remains obscure. We propose a simple model of the coexpression patterns in terms of spatial distributions of underlying cell types and establish its plausibility using independently measured cell-typespecific transcriptomes. The model allows us to predict the spatial distribution of cell types in the mouse brain

Simple models of small world networks with directed links

We investigate the effect of directed short and long range connections in a simple model of small world network. Our model is such that we can determine many quantities of interest by an exact analytical method. We calculate the function $V(T)$, defined as the number of sites affected up to time $T$ when a naive spreading process starts in the network. As opposed to shortcuts, the presence of un-favorable bonds has a negative effect on this quantity. Hence the spreading process may not be able to affect all the network. We define and calculate a quantity named the average size of accessible world in our model. The interplay of shortcuts, and un-favorable bonds on the small world properties is studied.Comment: 15 pages, 9 figures, published versio

Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page