New Drosophila Long-Term Memory Genes Revealed by Assessing Computational Function Prediction Methods

A major bottleneck to our understanding of the genetic and molecular foundation of life lies in the ability to assign function to a gene and, subsequently, a protein. Traditional molecular and genetic experiments can provide the most reliable forms of identification, but are generally low-throughput, making such discovery and assignment a daunting task. The bottleneck has led to an increasing role for computational approaches. The Critical Assessment of Functional Annotation (CAFA) effort seeks to measure the performance of computational methods. In CAFA3, we performed selected screens, including an effort focused on long-term memory. We used homology and previous CAFA predictions to identify 29 key Drosophila genes, which we tested via a long-term memory screen. We identify 11 novel genes that are involved in long-term memory formation and show a high level of connectivity with previously identified learning and memory genes. Our study provides first higher-order behavioral assay and organism screen used for CAFA assessments and revealed previously uncharacterized roles of multiple genes as possible regulators of neuronal plasticity at the boundary of information acquisition and memory formation.

[1]  Li Wang,et al.  Homeostatic Control of Hpo/MST Kinase Activity through Autophosphorylation-Dependent Recruitment of the STRIPAK PP2A Phosphatase Complex. , 2017, Cell reports.

[2]  Giovanni Bosco,et al.  Drosophila species learn dialects through communal living , 2017, bioRxiv.

[3]  Zhiping Weng,et al.  A systems level approach to temporal expression dynamics in Drosophila reveals clusters of long term memory genes , 2017, PLoS genetics.

[4]  Casey S Greene,et al.  Machine Learning Analysis Identifies Drosophila Grunge/Atrophin as an Important Learning and Memory Gene Required for Memory Retention and Social Learning , 2017, G3: Genes, Genomes, Genetics.

[5]  Mark Craven,et al.  A review of active learning approaches to experimental design for uncovering biological networks , 2017, PLoS Comput. Biol..

[6]  David T Jones,et al.  Computational Methods for Annotation Transfers from Sequence. , 2016, Methods in molecular biology.

[7]  Predrag Radivojac,et al.  Community-Wide Evaluation of Computational Function Prediction. , 2016, Methods in molecular biology.

[8]  J. Cerón,et al.  Minibrain drives the Dacapo-dependent cell cycle exit of neurons in the Drosophila brain by promoting asense and prospero expression , 2016, Development.

[9]  Hannah Currant,et al.  FFPred 3: feature-based function prediction for all Gene Ontology domains , 2016, Scientific Reports.

[10]  G. Miesenböck,et al.  Operation of a Homeostatic Sleep Switch , 2016, Nature.

[11]  T. Schlenke,et al.  Evolution of behavioural and cellular defences against parasitoid wasps in the Drosophila melanogaster subgroup , 2016, Journal of evolutionary biology.

[12]  Tapio Salakoski,et al.  An expanded evaluation of protein function prediction methods shows an improvement in accuracy , 2016, Genome Biology.

[13]  Raphael Cohn,et al.  Coordinated and Compartmentalized Neuromodulation Shapes Sensory Processing in Drosophila , 2015, Cell.

[14]  Mani Ramaswami,et al.  Social communication of predator-induced changes in Drosophila behavior and germ line physiology , 2015, eLife.

[15]  Olga G. Troyanskaya,et al.  IMP 2.0: a multi-species functional genomics portal for integration, visualization and prediction of protein functions and networks , 2015, Nucleic Acids Res..

[16]  Mani Ramaswami,et al.  A Novel Paradigm for Nonassociative Long-Term Memory in Drosophila: Predator-Induced Changes in Oviposition Behavior , 2015, Genetics.

[17]  G. Rubin,et al.  The neuronal architecture of the mushroom body provides a logic for associative learning , 2014, eLife.

[18]  Jie Tan,et al.  Big Data Bioinformatics , 2014, Journal of cellular physiology.

[19]  Mani Ramaswami,et al.  Network Plasticity in Adaptive Filtering and Behavioral Habituation , 2014, Neuron.

[20]  Balint Z. Kacsoh,et al.  A role for nematocytes in the cellular immune response of the Drosophilid Zaprionus indianus , 2014, Parasitology.

[21]  Pietro Perona,et al.  Tachykinin-Expressing Neurons Control Male-Specific Aggressive Arousal in Drosophila , 2014, Cell.

[22]  Simon G. Sprecher,et al.  Binary Cell Fate Decisions and Fate Transformation in the Drosophila Larval Eye , 2013, PLoS genetics.

[23]  Liu Yang,et al.  Riquiqui and Minibrain are regulators of the Hippo pathway downstream of Dachsous , 2013, Nature Cell Biology.

[24]  Hyo-Seok Chae,et al.  Natalisin, a tachykinin-like signaling system, regulates sexual activity and fecundity in insects , 2013, Proceedings of the National Academy of Sciences.

[25]  Mani Ramaswami,et al.  Altered Ribostasis: RNA-Protein Granules in Degenerative Disorders , 2013, Cell.

[26]  Gabriel Gasque,et al.  Small molecule drug screening in Drosophila identifies the 5HT2A receptor as a feeding modulation target , 2013, Scientific Reports.

[27]  Karin M. Verspoor,et al.  Combining heterogeneous data sources for accurate functional annotation of proteins , 2013, BMC Bioinformatics.

[28]  Nathan T Mortimer,et al.  Fruit Flies Medicate Offspring After Seeing Parasites , 2013, Science.

[29]  Slobodan Vucetic,et al.  MS-kNN: protein function prediction by integrating multiple data sources , 2013, BMC Bioinformatics.

[30]  Daniel W. A. Buchan,et al.  A large-scale evaluation of computational protein function prediction , 2013, Nature Methods.

[31]  J. Sweatt,et al.  Epigenetic regulation of memory formation and maintenance. , 2013, Learning & memory.

[32]  Julie H. Simpson,et al.  A GAL4-driver line resource for Drosophila neurobiology. , 2012, Cell reports.

[33]  Casey S Greene,et al.  Accurate evaluation and analysis of functional genomics data and methods , 2012, Annals of the New York Academy of Sciences.

[34]  Casey S. Greene,et al.  IMP: a multi-species functional genomics portal for integration, visualization and prediction of protein functions and networks , 2012, Nucleic Acids Res..

[35]  Vivian Budnik,et al.  Inhibitory Control of Synaptic and Behavioral Plasticity by Octopaminergic Signaling , 2012, The Journal of Neuroscience.

[36]  Balint Z. Kacsoh,et al.  High Hemocyte Load Is Associated with Increased Resistance against Parasitoids in Drosophila suzukii, a Relative of D. melanogaster , 2012, PloS one.

[37]  T. Lefèvre,et al.  Defence strategies against a parasitoid wasp in Drosophila: fight or flight? , 2012, Biology Letters.

[38]  D. Nässel,et al.  Insulin-producing cells in the brain of adult Drosophila are regulated by the serotonin 5-HT1A receptor , 2011, Cellular and Molecular Life Sciences.

[39]  Maria Leptin,et al.  Role for Traf4 in Polarizing Adherens Junctions as a Prerequisite for Efficient Cell Shape Changes , 2011, Molecular and Cellular Biology.

[40]  H. Shcherbata,et al.  New Dystrophin/Dystroglycan interactors control neuron behavior in Drosophila eye , 2011, BMC Neuroscience.

[41]  Subhabrata Sanyal,et al.  Plasticity of local GABAergic interneurons drives olfactory habituation , 2011, Proceedings of the National Academy of Sciences.

[42]  Mani Ramaswami,et al.  The Ataxin-2 protein is required for microRNA function and synapse-specific long-term olfactory habituation , 2011, Proceedings of the National Academy of Sciences.

[43]  Casey S. Greene,et al.  PILGRM: an interactive data-driven discovery platform for expert biologists , 2011, Nucleic Acids Res..

[44]  D. Nässel,et al.  The Serotonin 5-HT7Dro Receptor Is Expressed in the Brain of Drosophila, and Is Essential for Normal Courtship and Mating , 2011, PloS one.

[45]  H. Shcherbata,et al.  Stress and muscular dystrophy: a genetic screen for dystroglycan and dystrophin interactors in Drosophila identifies cellular stress response components. , 2011, Developmental biology.

[46]  Eric Blanc,et al.  Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat , 2011, The EMBO journal.

[47]  Olga G. Troyanskaya,et al.  Accurate Quantification of Functional Analogy among Close Homologs , 2011, PLoS Comput. Biol..

[48]  R. Xu,et al.  Motor coordination deficits in Alpk1 mutant mice with the inserted piggyBac transposon , 2011, BMC Neuroscience.

[49]  Marc Vidal,et al.  A Genome-Wide Gene Function Prediction Resource for Drosophila melanogaster , 2010, PloS one.

[50]  Yun Song,et al.  DMob4/Phocein Regulates Synapse Formation, Axonal Transport, and Microtubule Organization , 2010, The Journal of Neuroscience.

[51]  J. Dubnau,et al.  Genetic disruptions of Drosophila Pavlovian learning leave extinction learning intact , 2010, Genes, brain, and behavior.

[52]  G. Miesenböck,et al.  Writing Memories with Light-Addressable Reinforcement Circuitry , 2009, Cell.

[53]  Nicolas Y. Masse,et al.  Olfactory Information Processing in Drosophila , 2009, Current Biology.

[54]  Olga G. Troyanskaya,et al.  Global Prediction of Tissue-Specific Gene Expression and Context-Dependent Gene Networks in Caenorhabditis elegans , 2009, PLoS Comput. Biol..

[55]  Jason H. Moore,et al.  Sensible initialization using expert knowledge for genome-wide analysis of epistasis using genetic programming , 2009, 2009 IEEE Congress on Evolutionary Computation.

[56]  Ronald J. Nachman,et al.  Characterization and distribution of NKD, a receptor for Drosophila tachykinin-related peptide 6 , 2009, Peptides.

[57]  Olga G. Troyanskaya,et al.  Computationally Driven, Quantitative Experiments Discover Genes Required for Mitochondrial Biogenesis , 2009, PLoS genetics.

[58]  Kai Li,et al.  Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis , 2009, PLoS Comput. Biol..

[59]  Yoshinori Aso,et al.  The Mushroom Body of Adult Drosophila Characterized by GAL4 Drivers , 2009, Journal of neurogenetics.

[60]  Enrique Blanco,et al.  Coordinate control of synaptic-layer specificity and rhodopsins in photoreceptor neurons , 2008, Nature.

[61]  P. Shaw,et al.  D1 Receptor Activation in the Mushroom Bodies Rescues Sleep-Loss-Induced Learning Impairments in Drosophila , 2008, Current Biology.

[62]  Reinhard Ullmann,et al.  Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly. , 2008, American journal of human genetics.

[63]  Andrew G Clark,et al.  Contrasting Infection Strategies in Generalist and Specialist Wasp Parasitoids of Drosophila melanogaster , 2007, PLoS pathogens.

[64]  J. Collins,et al.  Large-Scale Mapping and Validation of Escherichia coli Transcriptional Regulation from a Compendium of Expression Profiles , 2007, PLoS biology.

[65]  S. Blair,et al.  Separating the adhesive and signaling functions of the Fat and Dachsous protocadherins , 2006, Development.

[66]  Michael I. Jordan,et al.  Protein Molecular Function Prediction by Bayesian Phylogenomics , 2005, PLoS Comput. Biol..

[67]  J. Dubnau,et al.  Deconstructing Memory in Drosophila , 2005, Current Biology.

[68]  Kazuo Emoto,et al.  Drosophila Mob family proteins interact with the related tricornered (Trc) and warts (Wts) kinases. , 2005, Molecular biology of the cell.

[69]  Ronald L. Davis,et al.  Thirty years of olfactory learning and memory research in Drosophila melanogaster , 2005, Progress in Neurobiology.

[70]  Stephan Frings,et al.  A family of octapamine receptors that specifically induce cyclic AMP production or Ca2+ release in Drosophila melanogaster , 2005 .

[71]  W. Quinn,et al.  Classical conditioning and retention in normal and mutantDrosophila melanogaster , 1985, Journal of Comparative Physiology A.

[72]  S. Blair,et al.  Interactions between Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing , 2004, Development.

[73]  Y. Carton,et al.  Ecological and genetic interactions in Drosophila-parasitoids communities: a case study with D. melanogaster, D. simulans and their common Leptopilina parasitoids in south-eastern France. , 2004 .

[74]  G. Mardon,et al.  Senseless represses nuclear transduction of Egfr pathway activation , 2004, Development.

[75]  Jan K Buitelaar,et al.  Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes. , 2004, American journal of human genetics.

[76]  Çoklu yazar Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes , 2004 .

[77]  Drosophila melanogaster, Drosophila simulans: So Similar, So Different , 2004, Contemporary Issues in Genetics and Evolution.

[78]  Ronald L. Davis,et al.  Spatiotemporal Rescue of Memory Dysfunction in Drosophila , 2003, Science.

[79]  M. Heisenberg,et al.  Dopamine and Octopamine Differentiate between Aversive and Appetitive Olfactory Memories in Drosophila , 2003, The Journal of Neuroscience.

[80]  Marc G Caron,et al.  Identification of Drosophila Neuropeptide Receptors by G Protein-coupled Receptors-β-Arrestin2 Interactions* , 2003, Journal of Biological Chemistry.

[81]  M. Schmid,et al.  Genome-Wide Insertional Mutagenesis of Arabidopsis thaliana , 2003, Science.

[82]  Alessandro Vespignani,et al.  Global protein function prediction from protein-protein interaction networks , 2003, Nature Biotechnology.

[83]  Shireen A. Davies,et al.  Systematic G-protein-coupled Receptor Analysis inDrosophila melanogaster Identifies a Leucokinin Receptor with Novel Roles* , 2002, The Journal of Biological Chemistry.

[84]  J. B. Duffy,et al.  GAL4 system in drosophila: A fly geneticist's swiss army knife , 2002, Genesis.

[85]  M. Sokolowski,et al.  Drosophila: Genetics meets behaviour , 2001, Nature Reviews Genetics.

[86]  Ronald L. Davis,et al.  P{Switch}, a system for spatial and temporal control of gene expression in Drosophila melanogaster , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[87]  Tim Tully,et al.  Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory , 2001, Nature.

[88]  P. Lasko The Drosophila melanogaster Genome: Translation Factors and RNA Binding Proteins , 2000 .

[89]  T. Brody,et al.  Drosophila melanogasterG Protein–Coupled Receptors , 2000, The Journal of cell biology.

[90]  M. Gerstein,et al.  Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores. , 2000, Journal of molecular biology.

[91]  T. Brody,et al.  Drosophila melanogaster G Protein–coupled Receptors , 2000 .

[92]  M Heisenberg,et al.  Tissue-specific expression of a type I adenylyl cyclase rescues the rutabaga mutant memory defect: in search of the engram. , 2000, Learning & memory.

[93]  Y. Ip,et al.  The mesoderm determinant Snail collaborates with related zinc‐finger proteins to control Drosophila neurogenesis , 1999, The EMBO journal.

[94]  G. Rubin,et al.  The Berkeley Drosophila Genome Project gene disruption project: Single P-element insertions mutating 25% of vital Drosophila genes. , 1999, Genetics.

[95]  D. Eisenberg,et al.  Detecting protein function and protein-protein interactions from genome sequences. , 1999, Science.

[96]  D. Eisenberg,et al.  Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[97]  C. K. Chen,et al.  The transcription factors KNIRPS and KNIRPS RELATED control cell migration and branch morphogenesis during Drosophila tracheal development. , 1998, Development.

[98]  J. Dubnau,et al.  Gene discovery in Drosophila: new insights for learning and memory. , 1998, Annual review of neuroscience.

[99]  Y. Nishida,et al.  A Novel Drosophila Receptor Tyrosine Kinase Expressed Specifically in the Nervous System , 1997, The Journal of Biological Chemistry.

[100]  Ronald L. Davis,et al.  DAMB, a Novel Dopamine Receptor Expressed Specifically in Drosophila Mushroom Bodies , 1996, Neuron.

[101]  R. Greenspan,et al.  Flies, genes, learning, and memory , 1995, Neuron.

[102]  M Heisenberg,et al.  minibrain: A new protein kinase family involved in postembryonic neurogenesis in Drosophila , 1995, Neuron.

[103]  T. Préat,et al.  Genetic dissection of consolidated memory in Drosophila , 1994, Cell.

[104]  Hugo J. Bellen,et al.  Mutations affecting the pattern of the PNS in drosophila reveal novel aspects of neuronal development , 1994, Neuron.

[105]  A. Baumann,et al.  Primary structure and functional characterization of a Drosophila dopamine receptor with high homology to human D1/5 receptors. , 1994, Receptors & channels.

[106]  I. Gauld,et al.  Parasitic Hymenoptera, biological control and biodiversity. , 1993 .

[107]  Ronald L. Davis,et al.  The Drosophila learning and memory gene rutabaga encodes a Ca 2+ calmodulin -responsive , 1992, Cell.

[108]  Lia Hemerik,et al.  Drosophila Species, Breeding in the Stinkhorn (Phallus Impudicus Pers.) and Their Larval Parasitoids , 1989 .

[109]  Tim Tully,et al.  Drosophila learning and memory revisited , 1987, Trends in Neurosciences.

[110]  C Helfrich,et al.  Role of the optic lobes in the regulation of the locomotor activity rhythm of Drosophila melanogaster: behavioral analysis of neural mutants. , 1986, Journal of neurogenetics.