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Article: Towards the integration of spatially and temporally resolved murine gene expression databases.

Sunkin, Susan M

2006 Volume 22, Issue 4, Page(s) 211–217

Abstract: Several large-scale projects are evaluating gene expression in the mouse brain, both spatially and temporally. These range from projects that cover a broad spectrum of genes and developmental stages to those with high-spatial resolution and gene coverage ...

Abstract	Several large-scale projects are evaluating gene expression in the mouse brain, both spatially and temporally. These range from projects that cover a broad spectrum of genes and developmental stages to those with high-spatial resolution and gene coverage but for only a single developmental stage. Each project contains its own self-consistent data set and tools for analysis and mining. Preliminary efforts are under way to construct tools and an infrastructure with which the data from across these different projects can be statistically pooled and analyzed. However, many obstacles remain, and these must be addressed and overcome soon if we are to unify the data sets, otherwise the preliminary efforts will be wasted. Here, the various projects for collecting and mining this information are reviewed, some challenges in data set comparisons are discussed, and some basic proposals are made for overcoming the challenges.
MeSH term(s)	Animals ; Brain/physiology ; Central Nervous System/anatomy & histology ; Central Nervous System/physiology ; Databases, Genetic ; Gene Expression ; Mice ; Software
Language	English
Publishing date	2006-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	619240-3
ISSN	1362-4555 ; 0168-9525 ; 0168-9479
ISSN (online)	1362-4555
ISSN	0168-9525 ; 0168-9479
DOI	10.1016/j.tig.2006.02.006
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Article: Insights from spatially mapped gene expression in the mouse brain.

Sunkin, Susan M / Hohmann, John G

Human molecular genetics

2007 Volume 16 Spec No. 2, Page(s) R209–19

Abstract: The growing number of publicly available databases of murine gene expression arising from genomic-scale transcriptome/proteome profiling projects allows open access to information about genes potentially involved in diseases and disorders of the brain. ... ...

Abstract	The growing number of publicly available databases of murine gene expression arising from genomic-scale transcriptome/proteome profiling projects allows open access to information about genes potentially involved in diseases and disorders of the brain. The use of various methodologies by myriad projects provides complementary types of information, ranging from easily quantifiable microarray data for gross brain regions, to transcript tag analysis and proteomic characterization. One mode of gene expression analysis that has recently been widely adopted is the utilization of colorimetric in situ hybridization. This approach is adaptable for high throughput production, and provides a reproducible, scaleable platform for large datasets. The Allen Brain Atlas in particular has utilized this technology to produce a genomic-scale anatomical digital atlas of gene expression in the adult male mouse brain. The availability of global datasets with cellular level spatial resolution, which can be easily parsed due to accessible informatics-derived image analysis tools, can provide both high level and detailed insights into gene regulation. This article reviews various gene expression profiling projects in the mouse brain, how these data sets are increasingly used to complement other studies and applications of these datasets to further understanding of neurological disease.
MeSH term(s)	Animals ; Autistic Disorder/genetics ; Brain/anatomy & histology ; Brain/metabolism ; Data Interpretation, Statistical ; Databases, Genetic ; Epilepsy/genetics ; Gene Expression ; Gene Expression Profiling ; Humans ; Male ; Mice ; Schizophrenia/genetics
Language	English
Publishing date	2007-10-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddm183
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Article ; Online: The Allen Brain Atlas: 5 years and beyond.

Jones, Allan R / Overly, Caroline C / Sunkin, Susan M

Nature reviews. Neuroscience

2009 Volume 10, Issue 11, Page(s) 821–828

Abstract: The Allen Brain Atlas, a Web-based, genome-wide atlas of gene expression in the adult mouse brain, was an experiment on a massive scale. The development of the atlas faced a combination of great technical challenges and a non-traditional open research ... ...

Abstract	The Allen Brain Atlas, a Web-based, genome-wide atlas of gene expression in the adult mouse brain, was an experiment on a massive scale. The development of the atlas faced a combination of great technical challenges and a non-traditional open research model, and it encountered many hurdles on the path to completion and community adoption. Having overcome these challenges, it is now a fundamental tool for neuroscientists worldwide and has set the stage for the creation of other similar open resources. Nevertheless, there are many untapped opportunities for exploration.
MeSH term(s)	Animals ; Atlases as Topic ; Brain/anatomy & histology ; Brain/physiology ; Forecasting ; Gene Expression Profiling/trends ; Humans ; Internet/trends ; Mice
Language	English
Publishing date	2009-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2034150-7
ISSN	1471-0048 ; 1471-0048 ; 1471-003X
ISSN (online)	1471-0048
ISSN	1471-0048 ; 1471-003X
DOI	10.1038/nrn2722
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Article ; Online: Transcripts with in silico predicted RNA structure are enriched everywhere in the mouse brain

Seemann Stefan E / Sunkin Susan M / Hawrylycz Michael J / Ruzzo Walter L / Gorodkin Jan

BMC Genomics, Vol 13, Iss 1, p

2012 Volume 214

Abstract: Abstract Background Post-transcriptional control of gene expression is mostly conducted by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration with specific binding proteins and RNAs. In several well characterized cases, these RNA ...

Abstract	Abstract Background Post-transcriptional control of gene expression is mostly conducted by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration with specific binding proteins and RNAs. In several well characterized cases, these RNA elements are known to form stable secondary structures. RNA secondary structures also may have major functional implications for long noncoding RNAs (lncRNAs). Recent transcriptional data has indicated the importance of lncRNAs in brain development and function. However, no methodical efforts to investigate this have been undertaken. Here, we aim to systematically analyze the potential for RNA structure in brain-expressed transcripts. Results By comprehensive spatial expression analysis of the adult mouse in situ hybridization data of the Allen Mouse Brain Atlas, we show that transcripts (coding as well as non-coding) associated with in silico predicted structured probes are highly and significantly enriched in almost all analyzed brain regions. Functional implications of these RNA structures and their role in the brain are discussed in detail along with specific examples. We observe that mRNAs with a structure prediction in their UTRs are enriched for binding, transport and localization gene ontology categories. In addition, after manual examination we observe agreement between RNA binding protein interaction sites near the 3’ UTR structures and correlated expression patterns. Conclusions Our results show a potential use for RNA structures in expressed coding as well as noncoding transcripts in the adult mouse brain, and describe the role of structured RNAs in the context of intracellular signaling pathways and regulatory networks. Based on this data we hypothesize that RNA structure is widely involved in transcriptional and translational regulatory mechanisms in the brain and ultimately plays a role in brain function.
Keywords	Genetics ; QH426-470 ; Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Genetics ; DOAJ:Biology ; DOAJ:Biology and Life Sciences ; Biotechnology ; TP248.13-248.65
Subject code	572
Language	English
Publishing date	2012-05-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
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Article ; Online: Exploration and visualization of connectivity in the adult mouse brain.

Feng, David / Lau, Chris / Ng, Lydia / Li, Yang / Kuan, Leonard / Sunkin, Susan M / Dang, Chinh / Hawrylycz, Michael

Methods (San Diego, Calif.)

2015 Volume 73, Page(s) 90–97

Abstract: The Allen Mouse Brain Connectivity Atlas is a mesoscale whole brain axonal projection atlas of the C57Bl/6J mouse brain. All data were aligned to a common template in 3D space to generate a comprehensive and quantitative database of inter-areal and cell- ... ...

Abstract	The Allen Mouse Brain Connectivity Atlas is a mesoscale whole brain axonal projection atlas of the C57Bl/6J mouse brain. All data were aligned to a common template in 3D space to generate a comprehensive and quantitative database of inter-areal and cell-type-specific projections. A suite of computational tools were developed to search and visualize the projection labeling experiments, available at http://connectivity.brain-map.org. We present three use cases illustrating how these publicly-available tools can be used to perform analyses of long range brain region connectivity. The use cases make extensive use of advanced visualization tools integrated with the atlas including projection density histograms, 3D computed anterograde and retrograde projection paths, and multi-specimen projection composites. These tools offer convenient access to detailed axonal projection information in the adult mouse brain and the ability to perform data analysis and visualization of projection fields and neuroanatomy in an integrated manner.
MeSH term(s)	Age Factors ; Animals ; Atlases as Topic ; Brain/anatomy & histology ; Brain/physiology ; Brain Mapping/methods ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Net/anatomy & histology ; Nerve Net/chemistry ; Nerve Net/physiology ; Neural Pathways/anatomy & histology ; Neural Pathways/chemistry ; Neural Pathways/physiology
Language	English
Publishing date	2015-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1066584-5
ISSN	1095-9130 ; 1046-2023
ISSN (online)	1095-9130
ISSN	1046-2023
DOI	10.1016/j.ymeth.2015.01.009
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Article ; Online: Spatial mapping of structural and connectional imaging data for the developing human brain with diffusion tensor imaging.

Ouyang, Austin / Jeon, Tina / Sunkin, Susan M / Pletikos, Mihovil / Sedmak, Goran / Sestan, Nenad / Lein, Ed S / Huang, Hao

Methods (San Diego, Calif.)

2015 Volume 73, Page(s) 27–37

Abstract: During human brain development from fetal stage to adulthood, the white matter (WM) tracts undergo dramatic changes. Diffusion tensor imaging (DTI), a widely used magnetic resonance imaging (MRI) modality, offers insight into the dynamic changes of WM ... ...

Abstract	During human brain development from fetal stage to adulthood, the white matter (WM) tracts undergo dramatic changes. Diffusion tensor imaging (DTI), a widely used magnetic resonance imaging (MRI) modality, offers insight into the dynamic changes of WM fibers as these fibers can be noninvasively traced and three-dimensionally (3D) reconstructed with DTI tractography. The DTI and conventional T1 weighted MRI images also provide sufficient cortical anatomical details for mapping the cortical regions of interests (ROIs). In this paper, we described basic concepts and methods of DTI techniques that can be used to trace major WM tracts noninvasively from fetal brain of 14 postconceptional weeks (pcw) to adult brain. We applied these techniques to acquire DTI data and trace, reconstruct and visualize major WM tracts during development. After categorizing major WM fiber bundles into five unique functional tract groups, namely limbic, brain stem, projection, commissural and association tracts, we revealed formation and maturation of these 3D reconstructed WM tracts of the developing human brain. The structural and connectional imaging data offered by DTI provides the anatomical backbone of transcriptional atlas of the developing human brain.
MeSH term(s)	Brain/embryology ; Brain/growth & development ; Brain/metabolism ; Brain Mapping/methods ; Child ; Child, Preschool ; Diffusion Tensor Imaging/methods ; Female ; Fetal Development/physiology ; Humans ; Male ; Pregnancy ; Statistics as Topic/methods ; White Matter/embryology ; White Matter/growth & development ; White Matter/metabolism
Language	English
Publishing date	2015-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1066584-5
ISSN	1095-9130 ; 1046-2023
ISSN (online)	1095-9130
ISSN	1046-2023
DOI	10.1016/j.ymeth.2014.10.025
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Article ; Online: Transcripts with in silico predicted RNA structure are enriched everywhere in the mouse brain.

Seemann, Stefan E / Sunkin, Susan M / Hawrylycz, Michael J / Ruzzo, Walter L / Gorodkin, Jan

BMC genomics

2012 Volume 13, Page(s) 214

Abstract: Background: Post-transcriptional control of gene expression is mostly conducted by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration with specific binding proteins and RNAs. In several well characterized cases, these RNA ... ...

Abstract	Background: Post-transcriptional control of gene expression is mostly conducted by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration with specific binding proteins and RNAs. In several well characterized cases, these RNA elements are known to form stable secondary structures. RNA secondary structures also may have major functional implications for long noncoding RNAs (lncRNAs). Recent transcriptional data has indicated the importance of lncRNAs in brain development and function. However, no methodical efforts to investigate this have been undertaken. Here, we aim to systematically analyze the potential for RNA structure in brain-expressed transcripts. Results: By comprehensive spatial expression analysis of the adult mouse in situ hybridization data of the Allen Mouse Brain Atlas, we show that transcripts (coding as well as non-coding) associated with in silico predicted structured probes are highly and significantly enriched in almost all analyzed brain regions. Functional implications of these RNA structures and their role in the brain are discussed in detail along with specific examples. We observe that mRNAs with a structure prediction in their UTRs are enriched for binding, transport and localization gene ontology categories. In addition, after manual examination we observe agreement between RNA binding protein interaction sites near the 3' UTR structures and correlated expression patterns. Conclusions: Our results show a potential use for RNA structures in expressed coding as well as noncoding transcripts in the adult mouse brain, and describe the role of structured RNAs in the context of intracellular signaling pathways and regulatory networks. Based on this data we hypothesize that RNA structure is widely involved in transcriptional and translational regulatory mechanisms in the brain and ultimately plays a role in brain function.
MeSH term(s)	Anatomy, Artistic ; Animals ; Atlases as Topic ; Brain/metabolism ; Cluster Analysis ; Computational Biology/methods ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks/genetics ; Genetic Variation ; In Situ Hybridization ; Mice ; Molecular Sequence Annotation ; Nucleic Acid Conformation ; Protein Binding/genetics ; RNA/chemistry ; RNA/genetics ; RNA Probes/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA, Untranslated/genetics ; RNA, Untranslated/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Thermodynamics ; Untranslated Regions/genetics
Chemical Substances	RNA Probes ; RNA, Messenger ; RNA, Untranslated ; RNA-Binding Proteins ; Untranslated Regions ; RNA (63231-63-0)
Language	English
Publishing date	2012-05-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2164
ISSN (online)	1471-2164
DOI	10.1186/1471-2164-13-214
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Article ; Online: Large-scale neuroinformatics for in situ hybridization data in the mouse brain.

Ng, Lydia L / Sunkin, Susan M / Feng, David / Lau, Chris / Dang, Chinh / Hawrylycz, Michael J

International review of neurobiology

2012 Volume 104, Page(s) 159–182

Abstract: Large-scale databases of the brain are providing content to the neuroscience community through molecular, cellular, functional, and connectomic data. Organization, presentation, and maintenance requirements are substantial given the complexity, diverse ... ...

Abstract	Large-scale databases of the brain are providing content to the neuroscience community through molecular, cellular, functional, and connectomic data. Organization, presentation, and maintenance requirements are substantial given the complexity, diverse modalities, resolution, and scale. In addition to microarrays, magnetic resonance imaging, and RNA sequencing, several in situ hybridization databases have been constructed due to their value in spatially localizing cellular expression. Scalable techniques for processing and presenting these data for maximum utility in viewing and analysis are key for end user value. We describe methods and use cases for the Allen Brain Atlas resources of the adult and developing mouse.
MeSH term(s)	Animals ; Brain/anatomy & histology ; Brain/metabolism ; Brain Mapping ; Computational Biology ; Databases, Factual ; Gene Expression/physiology ; In Situ Hybridization ; Mice
Language	English
Publishing date	2012
Publishing country	United States
Document type	Journal Article
ZDB-ID	209876-3
ISSN	2162-5514 ; 0074-7742
ISSN (online)	2162-5514
ISSN	0074-7742
DOI	10.1016/B978-0-12-398323-7.00007-0
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Article: An evolutionary driver of interspersed segmental duplications in primates

Genome biology. 2020 Dec., v. 21, no. 1

2020

Abstract: BACKGROUND: The complex interspersed pattern of segmental duplications in humans is responsible for rearrangements associated with neurodevelopmental disease, including the emergence of novel genes important in human brain evolution. We investigate the ... ...

Abstract	BACKGROUND: The complex interspersed pattern of segmental duplications in humans is responsible for rearrangements associated with neurodevelopmental disease, including the emergence of novel genes important in human brain evolution. We investigate the evolution of LCR16a, a putative driver of this phenomenon that encodes one of the most rapidly evolving human–ape gene families, nuclear pore interacting protein (NPIP). RESULTS: Comparative analysis shows that LCR16a has independently expanded in five primate lineages over the last 35 million years of primate evolution. The expansions are associated with independent lineage-specific segmental duplications flanking LCR16a leading to the emergence of large interspersed duplication blocks at non-orthologous chromosomal locations in each primate lineage. The intron-exon structure of the NPIP gene family has changed dramatically throughout primate evolution with different branches showing characteristic gene models yet maintaining an open reading frame. In the African ape lineage, we detect signatures of positive selection that occurred after a transition to more ubiquitous expression among great ape tissues when compared to Old World and New World monkeys. Mouse transgenic experiments from baboon and human genomic loci confirm these expression differences and suggest that the broader ape expression pattern arose due to mutational changes that emerged in cis. CONCLUSIONS: LCR16a promotes serial interspersed duplications and creates hotspots of genomic instability that appear to be an ancient property of primate genomes. Dramatic changes to NPIP gene structure and altered tissue expression preceded major bouts of positive selection in the African ape lineage, suggestive of a gene undergoing strong adaptive evolution.
Keywords	Cebidae ; Papio ; Pongidae ; brain ; evolutionary adaptation ; genes ; genetic instability ; genomics ; humans ; loci ; mice ; models ; nuclear pore ; open reading frames ; tissues
Language	English
Dates of publication	2020-12
Size	p. 202.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2040529-7
ISSN	1474-760X ; 1465-6906
ISSN (online)	1474-760X
ISSN	1465-6906
DOI	10.1186/s13059-020-02074-4
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Article ; Online: An evolutionary driver of interspersed segmental duplications in primates.

Genome biology

2020 Volume 21, Issue 1, Page(s) 202

Abstract: Background: The complex interspersed pattern of segmental duplications in humans is responsible for rearrangements associated with neurodevelopmental disease, including the emergence of novel genes important in human brain evolution. We investigate the ... ...

Abstract	Background: The complex interspersed pattern of segmental duplications in humans is responsible for rearrangements associated with neurodevelopmental disease, including the emergence of novel genes important in human brain evolution. We investigate the evolution of LCR16a, a putative driver of this phenomenon that encodes one of the most rapidly evolving human-ape gene families, nuclear pore interacting protein (NPIP). Results: Comparative analysis shows that LCR16a has independently expanded in five primate lineages over the last 35 million years of primate evolution. The expansions are associated with independent lineage-specific segmental duplications flanking LCR16a leading to the emergence of large interspersed duplication blocks at non-orthologous chromosomal locations in each primate lineage. The intron-exon structure of the NPIP gene family has changed dramatically throughout primate evolution with different branches showing characteristic gene models yet maintaining an open reading frame. In the African ape lineage, we detect signatures of positive selection that occurred after a transition to more ubiquitous expression among great ape tissues when compared to Old World and New World monkeys. Mouse transgenic experiments from baboon and human genomic loci confirm these expression differences and suggest that the broader ape expression pattern arose due to mutational changes that emerged in cis. Conclusions: LCR16a promotes serial interspersed duplications and creates hotspots of genomic instability that appear to be an ancient property of primate genomes. Dramatic changes to NPIP gene structure and altered tissue expression preceded major bouts of positive selection in the African ape lineage, suggestive of a gene undergoing strong adaptive evolution.
MeSH term(s)	Animals ; Biodiversity ; Brain ; Chromosome Mapping ; Chromosomes ; Evolution, Molecular ; Exons ; Gene Duplication ; Gene Fusion ; Genome, Human ; Genomic Instability ; Hominidae ; Humans ; Phylogeny ; Primates/genetics ; Segmental Duplications, Genomic
Language	English
Publishing date	2020-08-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2040529-7
ISSN	1474-760X ; 1474-760X
ISSN (online)	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-020-02074-4
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