Integrative approaches based on genomic techniques in the functional studies on enhancers.

With the development of sequencing technology and the dramatic drop in sequencing cost, the functions of noncoding genes are being characterized in a wide variety of fields (e.g. biomedicine). Enhancers are noncoding DNA elements with vital transcription regulation functions. Tens of thousands of enhancers have been identified in the human genome; however, the location, function, target genes and regulatory mechanisms of most enhancers have not been elucidated thus far. As high-throughput sequencing techniques have leapt forwards, omics approaches have been extensively employed in enhancer research. Multidimensional genomic data integration enables the full exploration of the data and provides novel perspectives for screening, identification and characterization of the function and regulatory mechanisms of unknown enhancers. However, multidimensional genomic data are still difficult to integrate genome wide due to complex varieties, massive amounts, high rarity, etc. To facilitate the appropriate methods for studying enhancers with high efficacy, we delineate the principles, data processing modes and progress of various omics approaches to study enhancers and summarize the applications of traditional machine learning and deep learning in multi-omics integration in the enhancer field. In addition, the challenges encountered during the integration of multiple omics data are addressed. Overall, this review provides a comprehensive foundation for enhancer analysis.

An oncogenic enhancer promotes melanoma progression via regulating ETV4 expression.

BACKGROUND: Enhancers are important gene regulatory elements that promote the expression of critical genes in development and disease. Aberrant enhancer can modulate cancer risk and activate oncogenes that lead to the occurrence of various cancers. However, the underlying mechanism of most enhancers in cancer remains unclear. Here, we aim to explore the function and mechanism of a crucial enhancer in melanoma. METHODS: Multi-omics data were applied to identify an enhancer (enh17) involved in melanoma progression. To evaluate the function of enh17, CRISPR/Cas9 technology were applied to knockout enh17 in melanoma cell line A375. RNA-seq, ChIP-seq and Hi-C data analysis integrated with luciferase reporter assay were performed to identify the potential target gene of enh17. Functional experiments were conducted to further validate the function of the target gene ETV4. Multi-omics data integrated with CUT&Tag sequencing were performed to validate the binding profile of the inferred transcription factor STAT3. RESULTS: An enhancer, named enh17 here, was found to be aberrantly activated and involved in melanoma progression. CRISPR/Cas9-mediated deletion of enh17 inhibited cell proliferation, migration, and tumor growth of melanoma both in vitro and in vivo. Mechanistically, we identified ETV4 as a target gene regulated by enh17, and functional experiments further support ETV4 as a target gene that is involved in cancer-associated phenotypes. In addition, STAT3 acts as a transcription factor binding with enh17 to regulate the transcription of ETV4. CONCLUSIONS: Our findings revealed that enh17 plays an oncogenic role and promotes tumor progression in melanoma, and its transcriptional regulatory mechanisms were fully elucidated, which may open a promising window for melanoma prevention and treatment.

The Mechanotransduction Signaling Pathways in the Regulation of Osteogenesis.

Bones are constantly exposed to mechanical forces from both muscles and Earth's gravity to maintain bone homeostasis by stimulating bone formation. Mechanotransduction transforms external mechanical signals such as force, fluid flow shear, and gravity into intracellular responses to achieve force adaptation. However, the underlying molecular mechanisms on the conversion from mechanical signals into bone formation has not been completely defined yet. In the present review, we provide a comprehensive and systematic description of the mechanotransduction signaling pathways induced by mechanical stimuli during osteogenesis and address the different layers of interconnections between different signaling pathways. Further exploration of mechanotransduction would benefit patients with osteoporosis, including the aging population and postmenopausal women.

GCReID: Generalized continual person re-identification via meta learning and knowledge accumulation.

Person re-identification (ReID) has made good progress in stationary domains. The ReID model must be retrained to adapt to new scenarios (domains) as they emerge unexpectedly, which leads to catastrophic forgetting. Continual learning trains the model in the order of domain emergence to alleviate catastrophic forgetting. However, generalization ability of the model is still limited due to the distribution difference between training and testing domains. To address the above problem, we propose the generalized continual person re-Identification (GCReID) model to continuously train an anti-forgetting and generalizable model. We endeavor to increase the diversity of samples by prior to simulate unseen domains. Meta-train and meta-test are adopted to enhance generalization of the model. Universal knowledge extracted from all seen domains and the simulated domains is stored in a set of feature embeddings. The knowledge is continually updated and applied to guide meta-train and meta-test via a graph attention network. Extensive experiments on 12 benchmark datasets and comparisons with 6 representative models demonstrate the effectiveness of the proposed model GCReID in enhancing generalization performance on unseen domains and alleviating catastrophic forgetting of seen domains. The code will be available at https://github.com/DFLAG-NEU/GCReID if our work is accepted.

Knowledge-Preserving continual person re-identification using Graph Attention Network.

Person re-identification (ReID), considered as a sub-problem of image retrieval, is critical for intelligent security. The general practice is to train a deep model on images from a particular scenario (also known as a domain) and perform retrieval tests on images from the same domain. Thus, the model has to be retrained to ensure good performance on unseen domains. Unfortunately, retraining will introduce the so called catastrophic forgetting problem existing in deep learning models. To address this problem, we propose a Continual person re-identification model via a Knowledge-Preserving (CKP) mechanism. The proposed model is able to accumulate knowledge from continuously changing scenarios. The knowledge is updated via a graph attention network from the human cognitive-inspired perspective as the scenario changes. The accumulated knowledge is used to guide the learning process of the proposed model on image samples from new-coming domains. We finally evaluate and compare CKP with fine-tuning, continual learning in image classification and person re-identification, and joint training. Experiments on representative benchmark datasets (Market1501, DukeMTMC, CUHK03, CUHK-SYSU, and MSMT17, which arrive in different orders) demonstrate the advantages of the proposed model in preventing forgetting, and experiments on other benchmark datasets (GRID, SenseReID, CUHK01, CUHK02, VIPER, iLIDS, and PRID, which are not available during training) demonstrate the generalization ability of the proposed model. The CKP outperforms the best comparative model by 0.58% and 0.65% on seen domains (datasets available during training), and by 0.95% and 1.02% on never seen domains (datasets not available during training) in terms of mAP and Rank1, respectively. Arrival order of the training datasets, guidance of accumulated knowledge for learning new knowledge and parameter settings are also discussed.