What defines cancer?Numerous factors have been found to be associated with cancer onset and development.Rudolf Virchow suggested some 150 years ago that cancer was causally linked to persistent irritation.Later studie...What defines cancer?Numerous factors have been found to be associated with cancer onset and development.Rudolf Virchow suggested some 150 years ago that cancer was causally linked to persistent irritation.Later studies have revealed that overexposure to radiation,persistent microbial infection,genetic mutations,and chronic(sterile)inflammation could all potentially lead to cancer,and the same has been observed about intermittent hypoxia,iron overload,and intake of certain “carcinogens”.In parallel,considerable information has been collected regarding animals that never or rarely develop cancer,such as blind mole rats and whales.Yet no general frameworks have been published that can functionally link potential drivers to the formation and progression of cancer in a predictable manner,which is consistent with the aforementioned and other epidemiological data.Here,we outline one such framework.展开更多
Acid–base homeostasis is a fundamental property of living cells,and its persistent disruption in human cells can lead to a wide range of diseases.In this study,we conducted a computational modeling analysis of transc...Acid–base homeostasis is a fundamental property of living cells,and its persistent disruption in human cells can lead to a wide range of diseases.In this study,we conducted a computational modeling analysis of transcriptomic data of 4750 human tissue samples of 9 cancer types in The Cancer Genome Atlas(TCGA)database.Built on our previous study,we quantitatively estimated the average production rate of OHby cytosolic Fenton reactions,which continuously disrupt the intracellular pH(pHi)homeostasis.Our predictions indicate that all or at least a subset of 43 reprogrammed metabolisms(RMs)are induced to produce net protons(H+)at comparable rates of Fenton reactions to keep the pHi stable.We then discovered that a number of wellknown phenotypes of cancers,including increased growth rate,metastasis rate,and local immune cell composition,can be naturally explained in terms of the Fenton reaction level and the induced RMs.This study strongly suggests the possibility to have a unified framework for studies of cancerinducing stressors,adaptive metabolic reprogramming,and cancerous behaviors.In addition,strong evidence is provided to demonstrate that a popular view that Na+/H+exchangers along with lactic acid exporters and carbonic anhydrases are responsible for the intracellular alkalization and extracellular acidification in cancer may not be justified.展开更多
Deep learning(DL)has shown explosive growth in its application to bioinformatics and has demonstrated thrillingly promising power to mine the complex relationship hidden in large-scale biological and biomedical data.A...Deep learning(DL)has shown explosive growth in its application to bioinformatics and has demonstrated thrillingly promising power to mine the complex relationship hidden in large-scale biological and biomedical data.A number of comprehensive reviews have been published on such applications,ranging from high-level reviews with future perspectives to those mainly serving as tutorials.展开更多
文摘What defines cancer?Numerous factors have been found to be associated with cancer onset and development.Rudolf Virchow suggested some 150 years ago that cancer was causally linked to persistent irritation.Later studies have revealed that overexposure to radiation,persistent microbial infection,genetic mutations,and chronic(sterile)inflammation could all potentially lead to cancer,and the same has been observed about intermittent hypoxia,iron overload,and intake of certain “carcinogens”.In parallel,considerable information has been collected regarding animals that never or rarely develop cancer,such as blind mole rats and whales.Yet no general frameworks have been published that can functionally link potential drivers to the formation and progression of cancer in a predictable manner,which is consistent with the aforementioned and other epidemiological data.Here,we outline one such framework.
基金supported by the National Science Foundation of USA(Grant No.2047631)and partially by Georgia Research Alliance,USA。
文摘Acid–base homeostasis is a fundamental property of living cells,and its persistent disruption in human cells can lead to a wide range of diseases.In this study,we conducted a computational modeling analysis of transcriptomic data of 4750 human tissue samples of 9 cancer types in The Cancer Genome Atlas(TCGA)database.Built on our previous study,we quantitatively estimated the average production rate of OHby cytosolic Fenton reactions,which continuously disrupt the intracellular pH(pHi)homeostasis.Our predictions indicate that all or at least a subset of 43 reprogrammed metabolisms(RMs)are induced to produce net protons(H+)at comparable rates of Fenton reactions to keep the pHi stable.We then discovered that a number of wellknown phenotypes of cancers,including increased growth rate,metastasis rate,and local immune cell composition,can be naturally explained in terms of the Fenton reaction level and the induced RMs.This study strongly suggests the possibility to have a unified framework for studies of cancerinducing stressors,adaptive metabolic reprogramming,and cancerous behaviors.In addition,strong evidence is provided to demonstrate that a popular view that Na+/H+exchangers along with lactic acid exporters and carbonic anhydrases are responsible for the intracellular alkalization and extracellular acidification in cancer may not be justified.
文摘Deep learning(DL)has shown explosive growth in its application to bioinformatics and has demonstrated thrillingly promising power to mine the complex relationship hidden in large-scale biological and biomedical data.A number of comprehensive reviews have been published on such applications,ranging from high-level reviews with future perspectives to those mainly serving as tutorials.
