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Recent deep learning models that predict the Hi-C contact map from DNA sequence achieve promising accuracy but cannot generalize to new cell types and or even capture differences among training cell types. We propose Epiphany, a neural network to predict cell-type-specific Hi-C contact maps from widely available epigenomic tracks. Epiphany uses bidirectional long short-term memory layers to capture long-range dependencies and optionally a generative adversarial network architecture to encourage contact map realism. Epiphany shows excellent generalization to held-out chromosomes within and across cell types, yields accurate TAD and interaction calls, and predicts structural changes caused by perturbations of epigenomic signals.
Assuntos
Cromossomos , Epigenômica , Redes Neurais de Computação , CromatinaRESUMO
The identification of cell-type-specific 3D chromatin interactions between regulatory elements can help to decipher gene regulation and to interpret the function of disease-associated non-coding variants. However, current chromosome conformation capture (3C) technologies are unable to resolve interactions at this resolution when only small numbers of cells are available as input. We therefore present ChromaFold, a deep learning model that predicts 3D contact maps and regulatory interactions from single-cell ATAC sequencing (scATAC-seq) data alone. ChromaFold uses pseudobulk chromatin accessibility, co-accessibility profiles across metacells, and predicted CTCF motif tracks as input features and employs a lightweight architecture to enable training on standard GPUs. Once trained on paired scATAC-seq and Hi-C data in human cell lines and tissues, ChromaFold can accurately predict both the 3D contact map and peak-level interactions across diverse human and mouse test cell types. In benchmarking against a recent deep learning method that uses bulk ATAC-seq, DNA sequence, and CTCF ChIP-seq to make cell-type-specific predictions, ChromaFold yields superior prediction performance when including CTCF ChIP-seq data as an input and comparable performance without. Finally, fine-tuning ChromaFold on paired scATAC-seq and Hi-C in a complex tissue enables deconvolution of chromatin interactions across cell subpopulations. ChromaFold thus achieves state-of-the-art prediction of 3D contact maps and regulatory interactions using scATAC-seq alone as input data, enabling accurate inference of cell-type-specific interactions in settings where 3C-based assays are infeasible.
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Introduction: Emergence agitation is a common postanaesthetic complication in children after sevofluraneanaesthesia. We aimed to compare the effects of ketamineand midazolam administered intravenously, before the endof surgery, for prevention of emergence agitation in childrenwho received caudal block for pain relief under sevofluraneanaesthesia.Material and Methods: 100 American Society ofAnaesthesiologists status I children aged 4-11 years scheduledfor inguinal hernia repair, circumcision or orchidopexywere enrolled to the study. Anaesthesia was induced withsevoflurane 8% in a mixture of 50% oxygen and nitrous oxide.After adequate depth of anaesthesia, a laryngeal mask wasplaced and caudal block was performed with 0.5 mL kg−1,0.125% bupivacaine. At the end of the surgery, ketamine0.25 mg kg−1 or midazolam 0.03 mg kg− were given to theirrespective groups. Agitation was assessed using PaediatricAnaesthesia Emergence Delirium scale and postoperative painwas evaluated with modified Children's Hospital of EasternOntario Pain Scale.Results and conclusion: modified Children's Hospital ofEastern Ontario Pain Scale scores were found higher inmidazolam group as compared to ketamine group at 0 minutesand 5 minutes while after 10 minutes, the scores becameinsignificant. Paediatric Anaesthesia Emergence Deliriumscores were found to be higher in midazolam group at 0, 5 and10 minutes as compared to ketamine group, but at 30 minutes,the delirium scores became comparable. Thus, ketaminewas able to prevent Emergence Delirium as well as decreasepain scores better than midazolam following sevofluraneanaesthesia in children with caudal block
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Introduction: Epidural anasthesia is a common method for anaesthetic management after lower limb orthopaedic surgery. The aim is to study the anesthetic effects along with hemodynamics and adverse effects, if any when fentanyl and dexmeditomidine are used as an adjuvant to 0.75% Ropivacaine in epidural anesthesia for major lower limb orthopaedic surgery. Material and methods: The study included 100 cases classified randomly into two groups (each=50): Group RF: Patient receiving epidural anesthesia with 15 ml of 0.75% Ropivacaine and 1microgram/kg Fentanyl. Group RD: Patients receiving epidural anesthesia with 15 ml of 0.75% Ropivacaine and 1microgram/Kg of Dexmeditomidine. Results: The quality of analgesia was better with dexmedetomidine than fentanyl group (p<0.05), andthe requirement for first rescue top up was significantly latter with dexmedetomidine than fentanyl group (p<0.05).In our study while comparing the adverse effects between the two groups we did not found any significant difference between the two groups statistically. The incidence of nausea and vomiting was higher in fentanyl group while incidences of urinary retention, shivering and dry mouth was higher in dexmedetomidine group. Conclusion: Dexmedetomidine is a better adjuvant to epidural ropivacaine compared to fentanyl for epidural anaesthesia in patients undergoing lower limb orthopaedic procedures.