The vast majority of missense variants observed in the human genome are of unknown clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on human and primate variant population frequency databases to predict missense variant pathogenicity. By combining structural context and evolutionary conservation, our model achieves state-of-the-art results across a wide range of genetic and experimental benchmarks, all without explicitly training on such data.
View Article and Find Full Text PDFWe describe the operation and improvement of AlphaFold, the system that was entered by the team AlphaFold2 to the "human" category in the 14th Critical Assessment of Protein Structure Prediction (CASP14). The AlphaFold system entered in CASP14 is entirely different to the one entered in CASP13. It used a novel end-to-end deep neural network trained to produce protein structures from amino acid sequence, multiple sequence alignments, and homologous proteins.
View Article and Find Full Text PDFProtein structures can provide invaluable information, both for reasoning about biological processes and for enabling interventions such as structure-based drug development or targeted mutagenesis. After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally determined structure. Here we markedly expand the structural coverage of the proteome by applying the state-of-the-art machine learning method, AlphaFold, at a scale that covers almost the entire human proteome (98.
View Article and Find Full Text PDFProteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort, the structures of around 100,000 unique proteins have been determined, but this represents a small fraction of the billions of known protein sequences. Structural coverage is bottlenecked by the months to years of painstaking effort required to determine a single protein structure.
View Article and Find Full Text PDFBackground: Neck stoma patient care involves significant clinical complexity. Inadequate staff training, equipment provision and infrastructure have all been highlighted as causes for avoidable patient harm.
Aims: To establish the perception of knowledge and confidence levels relating to the emergency management of neck stomas among UK nurses during the COVID-19 pandemic.
Int J Pediatr Otorhinolaryngol
November 2020
Introduction: Virtual outpatient clinics (VOPC) have been integrated into both paediatric and based adult outpatient services due to a multitude of factors, including increased demand for services, technological advances and rising morbidity secondary to ageing populations. The novel coronavirus disease (COVID-19) has accentuated pressures on the National Health Service (NHS) infrastructure, particularly elective services, whilst radically altering patterns of practice.
Aim: To evaluate the impact of the COVID-19 pandemic on paediatric otolaryngology outpatient services whilst collating patient feedback to elicit long-term sustainability post COVID-19.
Protein structure prediction can be used to determine the three-dimensional shape of a protein from its amino acid sequence. This problem is of fundamental importance as the structure of a protein largely determines its function; however, protein structures can be difficult to determine experimentally. Considerable progress has recently been made by leveraging genetic information.
View Article and Find Full Text PDFWe describe AlphaFold, the protein structure prediction system that was entered by the group A7D in CASP13. Submissions were made by three free-modeling (FM) methods which combine the predictions of three neural networks. All three systems were guided by predictions of distances between pairs of residues produced by a neural network.
View Article and Find Full Text PDFThe goal of this work is to recognise phrases and sentences being spoken by a talking face, with or without the audio. Unlike previous works that have focussed on recognising a limited number of words or phrases, we tackle lip reading as an open-world problem - unconstrained natural language sentences, and in the wild videos. Our key contributions are: (1) we compare two models for lip reading, one using a CTC loss, and the other using a sequence-to-sequence loss.
View Article and Find Full Text PDFCerebellopontine angle (CPA) tumours are the most common neoplasms in the posterior fossa, accounting for 5-10% of intracranial tumours. Most CPA tumours are benign, with most being vestibular schwannomas. Meningiomas arising from the jugular foramen are among the rarest of all with very few being described in the literature.
View Article and Find Full Text PDFJ Surg Case Rep
November 2014
Gastric volvulus is a rare condition with two forms of presentation, either acute or chronic. Since its discovery, there have been no cases of acute on chronic volvulus discussed in the literature. Its vague presentation makes diagnosis and subsequent management difficult.
View Article and Find Full Text PDFBackground: Myocardial infarction (MI) is a leading cause of death in the UK. A good clinical outcome depends on rapid treatment following the onset of symptoms. A person's knowledge of typical symptoms determines how quickly they present to the medical services.
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