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  1. Article: Model-Agnostic Neural Mean Field With The Refractory SoftPlus Transfer Function.

    Spaeth, Alex / Haussler, David / Teodorescu, Mircea

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Due to the complexity of neuronal networks and the nonlinear dynamics of individual neurons, it is challenging to develop a systems-level model which is accurate enough to be useful yet tractable enough to apply. Mean-field models which extrapolate from ... ...

    Abstract Due to the complexity of neuronal networks and the nonlinear dynamics of individual neurons, it is challenging to develop a systems-level model which is accurate enough to be useful yet tractable enough to apply. Mean-field models which extrapolate from single-neuron descriptions to large-scale models can be derived from the neuron's transfer function, which gives its firing rate as a function of its synaptic input. However, analytically derived transfer functions are applicable only to the neurons and noise models from which they were originally derived. In recent work, approximate transfer functions have been empirically derived by fitting a sigmoidal curve, which imposes a maximum firing rate and applies only in the diffusion limit, restricting applications. In this paper, we propose an approximate transfer function called Refractory SoftPlus, which is simple yet applicable to a broad variety of neuron types. Refractory SoftPlus activation functions allow the derivation of simple empirically approximated mean-field models using simulation results, which enables prediction of the response of a network of randomly connected neurons to a time-varying external stimulus with a high degree of accuracy. These models also support an accurate approximate bifurcation analysis as a function of the level of recurrent input. Finally, the model works without assuming large presynaptic rates or small postsynaptic potential size, allowing mean-field models to be developed even for populations with large interaction terms.
    Language English
    Publishing date 2024-02-06
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.05.579047
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Data sharing for pediatric cancers.

    Vaske, Olena Morozova / Haussler, David

    Science (New York, N.Y.)

    2019  Volume 363, Issue 6432, Page(s) 1125

    MeSH term(s) Child, Preschool ; Genomics ; Humans ; Information Dissemination/methods ; Medical Oncology ; Neoplasms/genetics ; Pediatrics ; United States
    Language English
    Publishing date 2019-03-14
    Publishing country United States
    Document type Editorial
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aax2739
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Life, the universe, and everything: an interview with David Haussler. Interviewed by Jane Gitschier.

    Haussler, David

    PLoS genetics

    2013  Volume 9, Issue 1, Page(s) e1003282

    MeSH term(s) Computational Biology ; Databases, Nucleic Acid ; Genome, Human ; Humans
    Language English
    Publishing date 2013-01-31
    Publishing country United States
    Document type Interview
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1003282
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Spiking neural state machine for gait frequency entrainment in a flexible modular robot.

    Spaeth, Alex / Tebyani, Maryam / Haussler, David / Teodorescu, Mircea

    PloS one

    2020  Volume 15, Issue 10, Page(s) e0240267

    Abstract: We propose a modular architecture for neuromorphic closed-loop control based on bistable relaxation oscillator modules consisting of three spiking neurons each. Like its biological prototypes, this basic component is robust to parameter variation but can ...

    Abstract We propose a modular architecture for neuromorphic closed-loop control based on bistable relaxation oscillator modules consisting of three spiking neurons each. Like its biological prototypes, this basic component is robust to parameter variation but can be modulated by external inputs. By combining these modules, we can construct a neural state machine capable of generating the cyclic or repetitive behaviors necessary for legged locomotion. A concrete case study for the approach is provided by a modular robot constructed from flexible plastic volumetric pixels, in which we produce a forward crawling gait entrained to the natural frequency of the robot by a minimal system of twelve neurons organized into four modules.
    MeSH term(s) Algorithms ; Animals ; Gait/physiology ; Humans ; Locomotion/physiology ; Models, Neurological ; Neural Networks, Computer ; Neurons/cytology ; Neurons/physiology ; Robotics ; Walking/physiology
    Language English
    Publishing date 2020-10-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0240267
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: David Haussler.

    Haussler, David

    Nature biotechnology

    2011  Volume 29, Issue 3, Page(s) 243

    MeSH term(s) Animals ; Chromosome Mapping/methods ; DNA/genetics ; Database Management Systems ; Databases, Genetic ; Genome/genetics ; Humans ; Information Storage and Retrieval/methods
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2011-03-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/nbt.1808
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Unraveling Neuronal Identities Using SIMS: A Deep Learning Label Transfer Tool for Single-Cell RNA Sequencing Analysis.

    Gonzalez-Ferrer, Jesus / Lehrer, Julian / O'Farrell, Ash / Paten, Benedict / Teodorescu, Mircea / Haussler, David / Jonsson, Vanessa D / Mostajo-Radji, Mohammed A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Large single-cell RNA datasets have contributed to unprecedented biological insight. Often, these take the form of cell atlases and serve as a reference for automating cell labeling of newly sequenced samples. Yet, classification algorithms have lacked ... ...

    Abstract Large single-cell RNA datasets have contributed to unprecedented biological insight. Often, these take the form of cell atlases and serve as a reference for automating cell labeling of newly sequenced samples. Yet, classification algorithms have lacked the capacity to accurately annotate cells, particularly in complex datasets. Here we present SIMS (Scalable, Interpretable Machine Learning for Single-Cell), an end-to-end data-efficient machine learning pipeline for discrete classification of single-cell data that can be applied to new datasets with minimal coding. We benchmarked SIMS against common single-cell label transfer tools and demonstrated that it performs as well or better than state of the art algorithms. We then use SIMS to classify cells in one of the most complex tissues: the brain. We show that SIMS classifies cells of the adult cerebral cortex and hippocampus at a remarkably high accuracy. This accuracy is maintained in trans-sample label transfers of the adult human cerebral cortex. We then apply SIMS to classify cells in the developing brain and demonstrate a high level of accuracy at predicting neuronal subtypes, even in periods of fate refinement, shedding light on genetic changes affecting specific cell types across development. Finally, we apply SIMS to single cell datasets of cortical organoids to predict cell identities and unveil genetic variations between cell lines. SIMS identifies cell-line differences and misannotated cell lineages in human cortical organoids derived from different pluripotent stem cell lines. When cell types are obscured by stress signals, label transfer from primary tissue improves the accuracy of cortical organoid annotations, serving as a reliable ground truth. Altogether, we show that SIMS is a versatile and robust tool for cell-type classification from single-cell datasets.
    Language English
    Publishing date 2023-11-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.28.529615
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Isoform-specific translational control is evolutionarily conserved in primates.

    Draper, Jolene M / Philipp, Julia / Neeb, Zachary T / Thomas, Richard / Katzman, Solomon / Salama, Sofie / Haussler, David / Sanford, Jeremy

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Alternative splicing (AS) alters messenger RNA (mRNA) coding capacity, localization, stability, and translation. Here we use comparative transcriptomics to identify cis-acting elements coupling AS to translational control (AS-TC). We sequenced total ... ...

    Abstract Alternative splicing (AS) alters messenger RNA (mRNA) coding capacity, localization, stability, and translation. Here we use comparative transcriptomics to identify cis-acting elements coupling AS to translational control (AS-TC). We sequenced total cytosolic and polyribosome-associated mRNA from human, chimpanzee, and orangutan induced pluripotent stem cells (iPSCs), revealing thousands of transcripts with splicing differences between subcellular fractions. We found both conserved and species-specific polyribosome association patterns for orthologous splicing events. Intriguingly, alternative exons with similar polyribosome profiles between species have stronger sequence conservation than exons with lineage-specific ribosome association. These data suggest that sequence variation underlies differences in the polyribosome association. Accordingly, single nucleotide substitutions in luciferase reporters designed to model exons with divergent polyribosome profiles are sufficient to regulate translational efficiency. We used position specific weight matrices to interpret exons with species-specific polyribosome association profiles, finding that polymorphic sites frequently alter recognition motifs for trans-acting RNA binding proteins. Together, our results show that AS can regulate translation by remodeling the cis-regulatory landscape of mRNA isoforms.
    Language English
    Publishing date 2023-05-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.04.21.537863
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Share pandemic sequences openly and fast.

    Haussler, David / Haeussler, Max / Hinrichs, Angie / Corbett-Detig, Russell / Bjork, Isabel

    Nature

    2021  Volume 591, Issue 7849, Page(s) 202

    Language English
    Publishing date 2021-03-03
    Publishing country England
    Document type Letter
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-021-00569-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: A complete pedigree-based graph workflow for rare candidate variant analysis.

    Markello, Charles / Huang, Charles / Rodriguez, Alex / Carroll, Andrew / Chang, Pi-Chuan / Eizenga, Jordan / Markello, Thomas / Haussler, David / Paten, Benedict

    Genome research

    2022  Volume 32, Issue 5, Page(s) 893–903

    Abstract: Methods that use a linear genome reference for genome sequencing data analysis are reference-biased. In the field of clinical genetics for rare diseases, a resulting reduction in genotyping accuracy in some regions has likely prevented the resolution of ... ...

    Abstract Methods that use a linear genome reference for genome sequencing data analysis are reference-biased. In the field of clinical genetics for rare diseases, a resulting reduction in genotyping accuracy in some regions has likely prevented the resolution of some cases. Pangenome graphs embed population variation into a reference structure. Although pangenome graphs have helped to reduce reference mapping bias, further performance improvements are possible. We introduce VG-Pedigree, a pedigree-aware workflow based on the pangenome-mapping tool of Giraffe and the variant calling tool DeepTrio using a specially trained model for Giraffe-based alignments. We demonstrate mapping and variant calling improvements in both single-nucleotide variants (SNVs) and insertion and deletion (indel) variants over those produced by alignments created using BWA-MEM to a linear-reference and Giraffe mapping to a pangenome graph containing data from the 1000 Genomes Project. We have also adapted and upgraded deleterious-variant (DV) detecting methods and programs into a streamlined workflow. We used these workflows in combination to detect small lists of candidate DVs among 15 family quartets and quintets of the Undiagnosed Diseases Program (UDP). All candidate DVs that were previously diagnosed using the Mendelian models covered by the previously published methods were recapitulated by these workflows. The results of these experiments indicate that a slightly greater absolute count of DVs are detected in the proband population than in their matched unaffected siblings.
    MeSH term(s) Genome ; High-Throughput Nucleotide Sequencing ; INDEL Mutation ; Pedigree ; Polymorphism, Single Nucleotide ; Software ; Workflow
    Language English
    Publishing date 2022-04-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.276387.121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Book ; Online: Spiking neural state machine for gait frequency entrainment in a flexible modular robot

    Spaeth, Alex / Tebyani, Maryam / Haussler, David / Teodorescu, Mircea

    2020  

    Abstract: We propose a modular architecture for neuromorphic closed-loop control based on bistable relaxation oscillator modules consisting of three spiking neurons each. Like its biological prototypes, this basic component is robust to parameter variation but can ...

    Abstract We propose a modular architecture for neuromorphic closed-loop control based on bistable relaxation oscillator modules consisting of three spiking neurons each. Like its biological prototypes, this basic component is robust to parameter variation but can be modulated by external inputs. By combining these modules, we can construct a neural state machine capable of generating the cyclic or repetitive behaviors necessary for legged locomotion. A concrete case study for the approach is provided by a modular robot constructed from flexible plastic volumetric pixels, in which we produce a forward crawling gait entrained to the natural frequency of the robot by a minimal system of twelve neurons organized into four modules.

    Comment: 22 pages, 11 figures
    Keywords Computer Science - Neural and Evolutionary Computing ; Computer Science - Robotics
    Publishing date 2020-07-14
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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