Biology subjects

Feng, G.

Publications and source records attributed to Feng, G..

6 recordsLinked to original sources

bioRxiv2018

Deep Convolutional Network for Animal Sound Classification and Source Attribution using Dual Audio Recordings

We introduce an end-to-end feedforward convolutional neural network that is able to reliably classify the source and type of animal calls in a noisy environment using two streams of audio data after being trained on a dataset of modest size and imperfect labels. The data consists of audio recordings from captive marmoset monkeys housed in pairs, with several other cages nearby. Our network can classify both the call type and which animal made it with a single pass through a single network using raw spectrogram images as input. The network vastly increases data analysis capacity for researchers interested in studying marmoset vocalizations, and allows data collection in the home cage, in group housed animals.

animal behavior and cognition↗

bioRxiv2018

Cyclin B3 is specifically required for metaphase to anaphase transition in mouse oocyte meiosis I

Meiosis, a cell division to generate gametes for sexual reproduction in eukaryotes, executes a single round of DNA replication and two successive rounds of chromosome segregation [1]. The extraordinary reliability of the meiotic cycle requires the activities of cyclin-dependent kinases (Cdks) associated with specific cyclins [2-4]. Cyclins are the regulatory subunits of protein kinases, which are the main regulators of maturation promoting factor or mitosis promoting factor (MPF) [5, 6] and anaphase-promoting complex/cyclosome (APC/C) [7, 8] in eukaryotic cell division. But how cyclins collaborate to control meiosis is still largely unknown. Cyclin B3 (Ccnb3) shares homology with A- and B-type cyclins [9], and is conserved during higher eukaryote evolution [10-17]. Previous studies have shown that Ccnb3-deleted females are sterile with oocytes unable to complete meiosis I in Drosophila [18], implying that Ccnb3 may have a special role in meiosis. To clarify the function of Ccnb3 in meiosis in mammalian species, we generated Ccnb3 mutant mice by CRISPR/Cas9, and found that Ccnb3 mutation caused female infertility with the failure of metaphase-anaphase transition in meiosis I. Ccnb3 was necessary for APC/C activation to initiate anaphase I, but not required for oocytes maturation, meiosis II progression, or early embryonic development. Our study reveals the differential cell cycle regulation between meiosis I and meiosis II, as well as meiosis between males and females, which shed light on the cell cycle control of meiosis.\n\nHighlightsO_LIIdentification of a female meiosis-specific cyclin in mouse\nC_LIO_LICyclin B3 is required for metaphase-anaphase transition in oocyte meiosis I\nC_LIO_LICyclin B3 is not essential for oocyte maturation and sister chromosome segregation\nC_LIO_LICyclin B3 is necessary for APC/C activation and MPF kinase activity through Cdk1\nC_LI

cell biology↗

bioRxiv2018

RNA Binding Motif Protein 48 is required for U12 splicing and maize endosperm differentiation

The last eukaryotic common ancestor had two classes of introns that are still found in most eukaryotic lineages. Common U2-type and rare U12-type introns are spliced by the major and minor spliceosomes, respectively. Relatively few splicing factors have been shown to be specific to the minor spliceosome. We found that the maize RNA Binding Motif Protein48 (RBM48) is a U12 splicing factor that functions to promote cell differentiation and repress cell proliferation. RBM48 is coselected with the U12 splicing factor, ZRSR2/RGH3. Protein-protein interactions between RBM48, RGH3, and U2 Auxiliary Factor (U2AF) subunits suggest major and minor spliceosome factors may form complexes during intron recognition. Human RBM48 interacts with ARMC7. Maize RBM48 and ARMC7 have a conserved protein-protein interaction. These data predict that RBM48 is likely to function in U12 splicing throughout eukaryotes and that U12 splicing promotes endosperm cell differentiation in maize.

plant biology↗

bioRxiv2018

RAD51 Enhances Zygotic Interhomolog Repair

Recent advances in genome editing have greatly improved knock-in (KI) efficiency1-9. Searching for factors to further improve KI efficiency for therapeutic use and generation of non-human primate (NHP) models, we found that the strand exchange protein RAD51 can significantly increase homozygous KI using CRISPR/Cas9 in mouse embryos through an interhomolog repair (IHR) mechanism. IHR is well-described in the context of meiosis10, but only occurs at low frequencies in mitotic cells11,12 and its existence in zygotes is controversial. Using a variety of approaches, we provide evidence for an endogenous IHR mechanism in zygotes that can be enhanced by RAD51. We show that this process can be harnessed for generating homozygous KI animals from wildtype zygotes based on exogenous donors and for converting heterozygous alleles into homozygous alleles without exogenous templates. Furthermore, we elucidate additional factors that contribute to zygotic IHR and identify a RAD51 mutant capable of insertion-deletion (indel)-free stimulation of IHR. Thus, our study provides conclusive evidence for the existence of zygotic IHR and demonstrates methods to enhance IHR for potential use in gene drives, gene therapy, and biotechnology.

molecular biology↗

bioRxiv2017

Evolutionarily Conserved Alternative Splicing Across Monocots

One difficulty when identifying and analyzing alternative splicing (AS) events in plants is distinguishing functional AS from splicing noise. One way to add confidence to the validity of a splice isoform is to observe that it is conserved across evolutionarily related species. We use a high throughput method to identify junction based conserved AS events from RNA-Seq data across nine plant species including: five grass monocots (maize, sorghum, rice, Brachpodium and foxtail millet), plus two non-grass monocots (bananan and African oil palm), the eudicot Arabidopsis and the basal angiosperm Amborella. In total, 9,804 conserved AS events within 19,235 genes were identified conserved between 2 or more species studied. In grasses containing large regions of conserved synteny, the frequency of conserved AS events is twice that observed for genes outside of conserved synteny blocks. In plant-specific RS and RS2Z subfamilies, we observe both conservation and divergence of AS events after the whole genome duplication in maize. In addition, plant-specific RS and RS2Z subfamilies are highly connected with R2R3-MYB in splicing networks. Furthermore, we discovered that the network based on genes harboring conserved AS events is enriched for phosphatases, kinases and ubiquitylation genes, which suggests that AS may participate in regulating signaling pathways. These data lay the foundation for identifying and studying conserved AS events in the monocots, particularly across grass species, and this conserved AS resource identifies an additional layer between genotype to phenotype that may impact future crop improvement efforts.

bioinformatics↗

bioRxiv2017

Evolutionary and functional data power search for obsessive-compulsive disorder genes

Obsessive-compulsive disorder (OCD) is a severe psychiatric disorder linked to abnormalities in the cortico-striatal circuit and in glutamate signaling. We sequenced coding and regulatory elements for 608 genes implicated in OCD from humans and two animal models (mouse and dog). Using a new method, PolyStrat, which prioritizes variants disrupting evolutionarily conserved, functional regions, we found four strongly associated genes when comparing 592 cases to 560 controls. These results were validated in a second, larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains, while CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants. The rare coding variant burden in NRXN1 achieves genomewide significance (p=6.37x10-11) when we include public data for 33,370 controls. Of 17 regulatory variants identified in CTTNBP2 and REEP3, we show that at least six alter transcription factor-DNA binding in human neuroblastoma cells. Our findings suggest synaptic adhesion as a key function in compulsive behaviors across three species, and demonstrate how combining targeted sequencing with functional annotations can identify potentially causative variants in both coding and noncoding regions, even when genomic data is limited.

genomics↗