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BackgroundThe Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.ResultsHere, 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. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory.ConclusionWe 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 the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.

Byline: Wei. Ding, Manxue. Yao, Yuting. Wang, Miaomiao. Wang, Yueqian. Zhu, Yan. Li, Zonghui. Li, Ling. Li, Wenxia. Ma, Ming. Liu, Naihui. Zhou Background: The management and treatment of psoriasis [...]

Background and aim: No previous study investigated the anatomical changes of the scalp and hair follicles between tertiary androgenetic alopecia and severe alopecia areata using high‐resolution magnetic resonance imaging (HR‐MRI). This study aimed to explore the value of HR‐MRI in assessing alopecia. Materials and methods: Forty‐eight people were included in this study. The imaging indicators of the vertex and occipital scalp were recorded and compared. The logistic regression model was developed for the indicators that differed between tertiary androgenetic alopecia and severe alopecia areata. The receiver‐operating characteristic (ROC) curve was used to assess the diagnostic efficacy of the model for tertiary androgenetic alopecia and severe alopecia areata. Results: At the vertex, the thickness of the subcutaneous tissue layer, follicle depth, relative follicle depth, total number of follicles within a 2‐cm distance, and number of strands reaching the middle and upper third of the subcutaneous fat layer within a 2‐cm distance were statistically different between patients with tertiary androgenetic alopecia, those with severe alopecia areata, and healthy volunteers (p < 0.05). The logistic regression model suggested that the subcutaneous tissue layer thickness was important in discriminating tertiary androgenetic alopecia from severe alopecia areata. The ROC curve showed that the area under the curve, sensitivity, specificity, and best cutoff values of the subcutaneous tissue layer were 0.886, 94.4%, 70%, and 4.31 mm, respectively. Conclusions: HR‐MRI can observe the changes in anatomical structures of the scalp and hair follicles in patients with alopecia. HR‐MRI can be applied to the differential diagnosis of tertiary androgenetic alopecia and severe alopecia areata. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Acne vulgaris (AV) is a chronic skin disease involving inflammation of the pilosebaceous units. Propionibacterium acnes ( P. acnes ) hypercolonization is one pathogenic factor for AV. P. acnes that triggers interleukin-1 β (IL-1 β ) by activating the pyrin domain-containing 3 protein (NLRP3) inflammasome of the NOD-like receptor family in human monocytes. Reactive oxygen species (ROS) acts as a trigger for the production of IL-8 and activates theNLRP3 inflammasome. IL-8 promotes the metastasis and multiplication of different cancerous cells, whereas keratinocyte proliferation and migration contribute to the progression of AV. A steroidal saponin called polyphyllin I (PPI) that is extracted from Paris polyphylla 's rhizomes has anti-inflammatory properties. This study investigates the regulatory role of P. acnes in the secretion of IL-8 mediated by the CD36/NADPH oxidase 1 (NOX1)/ROS/NLRP3/IL-1 β pathway and the effects of PPI on the CD36/NOX1/ROS/NLRP3/IL-1 β /IL-8 pathway and human keratinocyte proliferation and migration. HaCaT cells were cultured and stimulated with 10 8  CFU/ml of P. acnes for 0, 6, 12, 18, 24, 30, and 36 hours. P. acnes induced IL-8 secretion from HaCaT cells via the CD36/NOX1/ROS/NLRP3/IL-1 β pathway. PPI inhibited the CD36/NLRP3/NOX1/ROS/IL-8/IL-1 β pathway and HaCaT cell proliferation and migration. PPI alleviates P. acnes -induced inflammatory responses and human keratinocyte proliferation and migration, implying a novel potential therapy for AV., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Shuyun Yang et al.)