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相关概念视频

From DNA to Protein03:06

From DNA to Protein

18.0K
The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
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Leaky Scanning02:28

Leaky Scanning

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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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DNA as a Genetic Template02:05

DNA as a Genetic Template

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Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
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Transfer RNA Synthesis02:36

Transfer RNA Synthesis

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One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
11.9K
Improving Translational Accuracy02:07

Improving Translational Accuracy

9.3K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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The Central Dogma01:25

The Central Dogma

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Overview
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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
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一套基础模型捕捉了codons之间的上下文交互.

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概括

我们开发了cdsFM,这是一套大型语言模型,用于解码同义符号使用的功能影响. 这些模型预测了编码子选择如何影响蛋白质表达,并识别了潜在的致病性同义变体.

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Residue-specific Incorporation of Noncanonical Amino Acids into Model Proteins Using an Escherichia coli Cell-free Transcription-translation System
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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
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科学领域:

  • 计算生物学 计算生物学
  • 基因组学就是基因组学.
  • 分子生物学分子生物学

背景情况:

  • 遗传密码为许多氨基酸分配多个编码子 (同义编码子).
  • 同义代码子选择是非随机的,影响蛋白质功能和细胞调节.
  • 当前的蛋白质基础模型忽视了编码序列的调节作用.

研究的目的:

  • 介绍cdsFM,一个代码子分辨率的大型语言模型套件 (EnCodon和DeCodon),以解决理解同义代码子函数的差距.
  • 评估模型学习子-氨基酸关系的能力,并预测同义子使用情况.
  • 评估同名编码子变化对蛋白质表达和模型性能的影响.

主要方法:

  • 开发和预训练cdsFM (最多1B参数) 在5000多种物种的600万个蛋白质编码序列上.
  • 创建了一个数据集,测量在不同同名编码子环境下测量蛋白质表达水平.
  • 微调EnCodon模型以预测同义代码子选择的后果,并将其应用于临床数据集.

主要成果:

  • cdsFM模型有效地回顾了遗传代码结构,并在零射击和少数射击的学习任务中优于现有的基因组模型.
  • 较大的cdsFM模型显示出对同名编码子选择的优异预测.
  • 精心调整的EnCodon模型准确地预测了同名编码子变化的对蛋白质表达的影响,并确定了潜在的致病性同名变体.

结论:

  • cdsFM套件提供了一个强大的工具来解码同义代码使用的功能语法.
  • EnCodon模型可以微调,以预测同名编码子变化的上下文效应.
  • 该研究确定了许多可能的致病性同名编码子,经过实验验证,突出了它们的临床相关性.