Biology subjects

Kacsoh, B. Z.

Publications and source records attributed to Kacsoh, B. Z..

6 recordsLinked to original sources

bioRxiv2019

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Here we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility (P. aureginosa only). We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. We conclude that, while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. We finally report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bioontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.

bioinformatics↗

bioRxiv2019

Transgeneratonal inheritance of ethanol preference is caused by maternal NPF repression

Rapid or even anticipatory adaptation to environmental conditions can provide a decisive fitness advantage to an organism. The memory of recurring conditions could also benefit future generations, however neuronally-encoded behavior isnt thought to be inherited across generations. We tested the possibility that environmentally triggered modifications could allow "memory" of parental experiences to be inherited. In Drosophila melanogaster, exposure to predatory wasps leads to inheritance of a predisposition for ethanol-rich food for five generations. Inhibition of Neuropeptide-F (NPF) activates germline caspases required for transgenerational ethanol preference. Further, inheritance of low NPF expression in specific regions of F1 brains is required for the transmission of this food preference: A maternally derived NPF locus is necessary for this phenomenon, implicating a maternal epigenetic mechanism of NPF-repression. Given the conserved signaling functions of NPF and its mammalian NPY homolog in drug and alcohol disorders, these observations raise the intriguing possibility of NPY-related transgenerational effects in humans.

molecular biology↗

bioRxiv2019

Neural circuitry of dialects through social learning in Drosophila.

Drosophila species communicate the presence of parasitoid wasps to naive individuals. This observation suggests a rudimentary Drosophila social structure. Communication between closely related species is efficient, while more distantly related species exhibit a dampened, partial communication. Partial communication between some species is enhanced following a period of cohabitation, suggesting that species-specific variations in communication "dialects" can be learned through social interactions. However, it remains unclear as to how the behavioral acquisition and how learning dialects is facilitated by distinct brain regions. In this study, we have identified six regions of the Drosophila brain essential for dialect learning, including the odorant receptor Or69a. Furthermore, we pinpoint subgroups of neurons such as motion detecting neurons in the optic lobe, layer 5 of the fan-shaped body, and the D glomerulus in the antennal lobe, where activation of each are necessary for dialect learning. These results demonstrate that Drosophila can display complex social behaviors with inputs to multiple regions of the Drosophila brain and unique subsets of neurons that must integrate olfactory, visual and motion cues.

neuroscience↗

bioRxiv2018

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.

neuroscience↗

bioRxiv2017

Drosophila species learn dialects through communal living

Many species are able to share information about their environment by communicating through auditory, visual, and olfactory cues. In Drosophila melanogaster, exposure to parasitoid wasps leads to a decline in egg laying, and exposed females communicate this threat to naive flies, which also depress egg laying. We find that species across the genus Drosophila respond to wasps by egg laying reduction, activate cleaved caspase in oocytes, and communicate the presence of wasps to naive individuals. communication within a species and between closely related species is efficient, while more distantly related species exhibit partial communication. Remarkably, partial communication between some species is enhanced after a cohabitation period that requires exchange of visual and olfactory signals. This interspecies \"dialect learning\" requires neuronal cAMP signaling in the mushroom body, suggesting neuronal plasticity facilitates dialect learning and memory. These observations establish Drosophila as genetic models for inter-species social communication and evolution of dialects.

genomics↗

bioRxiv2017

Machine learning analysis identifies Drosophila Grunge/Atrophin as an important learning and memory gene required for memory retention and social learning.

High throughput experiments are becoming increasingly common, and scientists must balance hypothesis driven experiments with genome wide data acquisition. We sought to predict novel genes involved in Drosophila learning and long-term memory from existing public high-throughput data. We performed an analysis using PILGRM, which analyzes public gene expression compendia using machine learning. We evaluated the top prediction alongside genes involved in learning and memory in IMP, an interface for functional relationship networks. We identified Grunge/Atrophin (Gug/Atro), a transcriptional repressor, histone deacetylase, as our top candidate. We find, through multiple, distinct assays, that Gug has an active role as a modulator of memory retention in the fly and its function is required in the adult mushroom body. Depletion of Gug specifically in neurons of the adult mushroom body, after cell division and neuronal development is complete, suggests that Gug function is important for memory retention through regulation of neuronal activity, and not by altering neurodevelopment. Our study provides a previously uncharacterized role for Gug as a possible regulator of neuronal plasticity at the interface of memory retention and memory extinction.

genetics↗