抗生物質の作用メカニズムを明らかにするためのホワイトボックスの機械学習アプローチ
Jason H Yang1, Sarah N Wright1, Meagan Hamblin2
1Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell
|May 14, 2019
まとめ
生物学的スクリーニング,ネットワークモデリング,機械学習を組み合わせた 新しいアプローチを開発し 生物学的信号と表型の間の因果関係を明らかにし 抗生物質の有効性のメカニズムを明らかにしました
科学分野:
- 生物化学
- システム生物学
- 機械学習
背景:
- 現在の機械学習方法は 生物学的信号と現象型を 関連付けるのに優れているが 因果関係を確立することはできません
- 薬の発見と有効性研究を進めるには 原因メカニズムを理解することが重要です
研究 の 目的:
- 抗生物質の有効性の基礎となる因果メカニズムを特定するための統合的アプローチを開発し,適用する.
- 抗生物質に対する細菌の反応における代謝状態の役割を解明する.
主な方法:
- バイオケミカルスクリーニング,ゲノムスケールの代謝ネットワークモデリング,機械学習を統合した"ホワイトボックス"アプローチを開発した.
- エシェリキア・コリ菌における抗菌剤に対する代謝物の対スクリーニングを行った.
- メタボリックネットワークモデルとシミュレーションに対する回帰スクリーニングデータを用いてシミュレーションされた代謝状態.
主要な成果:
- 抗生物質の致死性の重要な要因として ピューリン生物合成を特定した.
- 抗生物質によるアデニン制限がATPの需要と中央の炭素代謝を高めることを示した.
- 代謝活動が増加すると 抗生物質の殺菌効果が強化されます
結論:
- 統合されたネットワークモデリングと機械学習のアプローチは,複雑な因果メカニズムを特定することができます.
- 代謝障害,特にアデニンの制限は,抗生物質の有効性に大きな影響を与えます.
- この枠組みは 薬物への反応を理解し 予測する道を示しています
キーワード:
ATP についてLC-MS/MS についてNADPH:NADP ((+) の比率についてアデニラートエネルギー抗生物質生化学スクリーニング機械学習メタボリズムネットワークモデリングピューリン生物合成さらに関連する動画
関連する概念動画
01:14Mechanical Efficiency of Real Machines
1.3K
The mechanical efficiency of a machine is a fundamental concept that describes how effectively a machine can convert input work into output work. According to this concept, the efficiency of a machine is equal to the ratio of the output work to the input work. An ideal machine, meaning a machine that has no energy losses, has an efficiency of one. This implies that the input work and the output work are equal.
However, in reality, no machine can be truly ideal, and all of them experience some...
However, in reality, no machine can be truly ideal, and all of them experience some...
1.3K
01:28Depolarizing Blockers: Mechanism of Action
2.8K
Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
2.8K
01:23Local Anesthetics: Mechanism of Action
3.3K
Local anesthetics (LAs) block sensory and motor impulses by inhibiting the sodium channels on the nerve cell membranes. This induces temporary loss of sensation, relieving pain in a specific body area.
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
3.3K
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
2.5K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
2.5K
01:17Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action
2.8K
Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
2.8K
00:57Antibiotic Selection
59.6K
Overview
59.6K