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1. tRFtarget: a database for transfer RNA-derived fragment targets

   https://doi.org/10.1093/nar/gkaa831  

   Li, Ningshan; Shan, Nayang; Lu, Lingeng; Wang, Zuoheng (October 2020, Nucleic Acids Research)

   null (Ed.)

   Abstract Transfer RNA-derived fragments (tRFs) are a new class of small non-coding RNAs and play important roles in biological and physiological processes. Prediction of tRF target genes and binding sites is crucial in understanding the biological functions of tRFs in the molecular mechanisms of human diseases. We developed a publicly accessible web-based database, tRFtarget (http://trftarget.net), for tRF target prediction. It contains the computationally predicted interactions between tRFs and mRNA transcripts using the two state-of-the-art prediction tools RNAhybrid and IntaRNA, including location of the binding sites on the target, the binding region, and free energy of the binding stability with graphic illustration. tRFtarget covers 936 tRFs and 135 thousand predicted targets in eight species. It allows researchers to search either target genes by tRF IDs or tRFs by gene symbols/transcript names. We also integrated the manually curated experimental evidence of the predicted interactions into the database. Furthermore, we provided a convenient link to the DAVID® web server to perform downstream functional pathway analysis and gene ontology annotation on the predicted target genes. This database provides useful information for the scientific community to experimentally validate tRF target genes and facilitate the investigation of the molecular functions and mechanisms of tRFs. 

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2. Virtual Screening of Molecules via Neural Fingerprint-based Deep Learning Technique

   https://doi.org/10.21203/rs.3.rs-4355625/v1  

   Monsia, Rivaaj; Bhattacharyya, Sudeep (May 2024, Research Square)

   Abstract A machine learning-based drug screening technique has been developed and optimized using convolutional neural network-derived fingerprints. The optimization of weights in the neural network-based fingerprinting technique was compared with fixed Morgan fingerprints in regard to binary classification on drug-target binding affinity. The assessment was carried out using six different target proteins using randomly chosen small molecules from the ZINC15 database for training. This new architecture proved to be more efficient in screening molecules that less favorably bind to specific targets and retaining molecules that favorably bind to it. Scientific contribution We have developed a new neural fingerprint-based screening model that has a significant ability to capture hits. Despite using a smaller dataset, this model is capable of mapping chemical space similar to other contemporary algorithms designed for molecular screening. The novelty of the present algorithm lies in the speed with which the models are trained and tuned before testing its predictive capabilities and hence is a significant step forward in the field of machine learning-embedded computational drug discovery. 

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3. ConnecTF: A platform to integrate transcription factor–gene interactions and validate regulatory networks

   https://doi.org/10.1093/plphys/kiaa012  

   Brooks, Matthew D; Juang, Che-Lun; Katari, Manpreet Singh; Alvarez, José M; Pasquino, Angelo; Shih, Hung-Jui; Huang, Ji; Shanks, Carly; Cirrone, Jacopo; Coruzzi, Gloria M (November 2020, Plant Physiology)

   null (Ed.)

   Abstract Deciphering gene regulatory networks (GRNs) is both a promise and challenge of systems biology. The promise lies in identifying key transcription factors (TFs) that enable an organism to react to changes in its environment. The challenge lies in validating GRNs that involve hundreds of TFs with hundreds of thousands of interactions with their genome-wide targets experimentally determined by high-throughput sequencing. To address this challenge, we developed ConnecTF, a species-independent, web-based platform that integrates genome-wide studies of TF–target binding, TF–target regulation, and other TF-centric omic datasets and uses these to build and refine validated or inferred GRNs. We demonstrate the functionality of ConnecTF by showing how integration within and across TF–target datasets uncovers biological insights. Case study 1 uses integration of TF–target gene regulation and binding datasets to uncover TF mode-of-action and identify potential TF partners for 14 TFs in abscisic acid signaling. Case study 2 demonstrates how genome-wide TF–target data and automated functions in ConnecTF are used in precision/recall analysis and pruning of an inferred GRN for nitrogen signaling. Case study 3 uses ConnecTF to chart a network path from NLP7, a master TF in nitrogen signaling, to direct secondary TF2s and to its indirect targets in a Network Walking approach. The public version of ConnecTF (https://ConnecTF.org) contains 3,738,278 TF–target interactions for 423 TFs in Arabidopsis, 839,210 TF–target interactions for 139 TFs in maize (Zea mays), and 293,094 TF–target interactions for 26 TFs in rice (Oryza sativa). The database and tools in ConnecTF will advance the exploration of GRNs in plant systems biology applications for model and crop species. 

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4. Joint Learning of 3D Shape Retrieval and Deformation

   Uy, Mikaela Angelina; Kim, Vladimir G.; Sung, Minhyuk; Aigerman, Noam; Chaudhuri, Siddhartha; Guibas, Leonidas (January 2021, Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition)

   null (Ed.)

   We propose a novel technique for producing high-quality 3D models that match a given target object image or scan. Our method is based on retrieving an existing shape from a database of 3D models and then deforming its parts to match the target shape. Unlike previous approaches that independently focus on either shape retrieval or deformation, we propose a joint learning procedure that simultaneously trains the neural deformation module along with the embedding space used by the retrieval module. This enables our network to learn a deformation-aware embedding space, so that retrieved models are more amenable to match the target after an appropriate deformation. In fact, we use the embedding space to guide the shape pairs used to train the deformation module, so that it invests its capacity in learning deformations between meaningful shape pairs. Furthermore, our novel part-aware deformation module can work with inconsistent and diverse part-structures on the source shapes. We demonstrate the benefits of our joint training not only on our novel framework, but also on other state-of-the-art neural deformation modules proposed in recent years. Lastly, we also show that our jointly-trained method outperforms various non-joint baselines. 

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5. CANDI: a web server for predicting molecular targets and pathways of cannabis-based therapeutics

   https://doi.org/10.1186/s42238-025-00268-w  

   Ekambaram, Srinivasan; Wang, Jian; Dokholyan, Nikolay_V (February 2025, Journal of Cannabis Research)

   Abstract BackgroundCannabis sativaL. with a rich history of traditional medicinal use, has garnered significant attention in contemporary research for its potential therapeutic applications in various human diseases, including pain, inflammation, cancer, and osteoarthritis. However, the specific molecular targets and mechanisms underlying the synergistic effects of its diverse phytochemical constituents remain elusive. Understanding these mechanisms is crucial for developing targeted, effective cannabis-based therapies. MethodsTo investigate the molecular targets and pathways involved in the synergistic effects of cannabis compounds, we utilized DRIFT, a deep learning model that leverages attention-based neural networks to predict compound-target interactions. We considered both whole plant extracts and specific plant-based formulations. Predicted targets were then mapped to the Reactome pathway database to identify the biological processes affected. To facilitate the prediction of molecular targets and associated pathways for any user-specified cannabis formulation, we developed CANDI (Cannabis-derived compound Analysis and Network Discovery Interface), a web-based server. This platform offers a user-friendly interface for researchers and drug developers to explore the therapeutic potential of cannabis compounds. ResultsOur analysis using DRIFT and CANDI successfully identified numerous molecular targets of cannabis compounds, many of which are involved in pathways relevant to pain, inflammation, cancer, and other diseases. The CANDI server enables researchers to predict the molecular targets and affected pathways for any specific cannabis formulation, providing valuable insights for developing targeted therapies. ConclusionsBy combining computational approaches with knowledge of traditional cannabis use, we have developed the CANDI server, a tool that allows us to harness the therapeutic potential of cannabis compounds for the effective treatment of various disorders. By bridging traditional pharmaceutical development with cannabis-based medicine, we propose a novel approach for botanical-based treatment modalities. 

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