Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across dif...Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.展开更多
It has been observed that both cancer tissue cells and normal proliferating cells(NPCs)have the Warburg effect.Our goal here is to demonstrate that they do this for different reasons.To accomplish this,we have analyze...It has been observed that both cancer tissue cells and normal proliferating cells(NPCs)have the Warburg effect.Our goal here is to demonstrate that they do this for different reasons.To accomplish this,we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer types in TCGA and data of five NPC types in GEO.Our analyses reveal that NPCs accumulate large quantities of ATPs produced by the respiration process before starting the Warburg effect,to raise the intracellular pH from 6.8 to 7.2 and to prepare for cell division energetically.Once cell cycle starts,the cells start to rely on glycolysis for ATP generation followed by ATP hydrolysis and lactic acid release,to maintain the elevated intracellular pH as needed by cell division since together the three processes are pH neutral.The cells go back to the normal respirationbased ATP production once the cell division phase ends.In comparison,cancer cells have reached their intracellular pH at 7.4 from top down as multiple acid-loading transporters are up-regulated and most acid-extruding ones except for lactic acid exporters are repressed.Cancer cells use continuous glycolysis for ATP production as way to acidify the intracellular space since the lactic acid secretion is decoupled from glycolysis-based ATP generation and is pH balanced by increased expressions of acid-loading transporters.Co-expression analyses suggest that lactic acid secretion is regulated by external,non-pH related signals.Overall,our data strongly suggest that the two cell types have the Warburg effect for very different reasons.展开更多
While some pseudogenes have been reported to play important roles in gene regulation, little is known about the possible relationship between pseudogene functions and evolutionary process of pseudogenes, or about the ...While some pseudogenes have been reported to play important roles in gene regulation, little is known about the possible relationship between pseudogene functions and evolutionary process of pseudogenes, or about the forces responsible for the pseudogene evolution. In this study, we characterized human processed pseudogenes in terms of evolutionary dynamics. Our results show that pseudogenes tend to evolve toward: lower GC content, strong dinucleotide bias, reduced abundance of transcription factor binding motifs and short palindromes, and decreased ability to form nucleosomes. We explored possible evolutionary forces that shaped the evolution pattern of pseudogenes, and concluded that mutations in pseudogenes are likely determined, at least partially, by neighbor-dependent mutational bias and recombination-associated selection.展开更多
Lactates play key roles in facilitating or protecting the development of a cancer in most cancer types.While its beneficial effects to cancer development have been extensively studied,very little is known about what d...Lactates play key roles in facilitating or protecting the development of a cancer in most cancer types.While its beneficial effects to cancer development have been extensively studied,very little is known about what derives the high-level production of lactates in a cancer throughout its entire development.Here we present a novel computational analysis of transcriptomic data of nine primary cancer types,plus a few precancerous and metastatic cancer,to address this issue.Our approach is to identify stress types,which are known to play key roles in cancer development and show strong co-expressions with lactate dehydrogenase-A(LDHA),at different stages of cancer development.A number of interesting observations are made through our analyses,including(i)all nine primary cancer types show similar association patterns between stresses and LDHA,namely the strengths of the associations increase from early-to intermediate-stage cancer tissues but then make a substantial down turn at the most advanced stage;(ii)while the detailed stress types associated with LDHA may vary across different cancer types,stresses induced by apoptosis and adaptive immune responses are present universally,suggesting that these two stresses are possibly two key drivers to keep the high-level production of lactates;and(iii)there is a clear distinction between stress types associated with LDHA in precancerous tissues vs.cancer and metastasis tissues.We anticipate that the analyses can provide highly useful information for designing personalized treatments for different cancers at different stages,as stopping lactate production could have devastating effects on a cancer development.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
基金supported by Georgia Research Alliance and the National Natural Science Foundation of China(Grant Nos.81320108025,61402194,61572227)the Science-Technology Development Project from Jilin Province(Nos.20160101259JC,20160204022GX,20170520063JH)
文摘Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.
基金funding support from Georgia Research Alliance,the National Natural Science Foundation of China(Grant Nos.61472158,61572228,and 61572227)the Premier-Discipline Enhancement Scheme supported by Zhuhai Government and Premier Key-Discipline Enhancement Scheme supported by Guangdong Government,China
文摘It has been observed that both cancer tissue cells and normal proliferating cells(NPCs)have the Warburg effect.Our goal here is to demonstrate that they do this for different reasons.To accomplish this,we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer types in TCGA and data of five NPC types in GEO.Our analyses reveal that NPCs accumulate large quantities of ATPs produced by the respiration process before starting the Warburg effect,to raise the intracellular pH from 6.8 to 7.2 and to prepare for cell division energetically.Once cell cycle starts,the cells start to rely on glycolysis for ATP generation followed by ATP hydrolysis and lactic acid release,to maintain the elevated intracellular pH as needed by cell division since together the three processes are pH neutral.The cells go back to the normal respirationbased ATP production once the cell division phase ends.In comparison,cancer cells have reached their intracellular pH at 7.4 from top down as multiple acid-loading transporters are up-regulated and most acid-extruding ones except for lactic acid exporters are repressed.Cancer cells use continuous glycolysis for ATP production as way to acidify the intracellular space since the lactic acid secretion is decoupled from glycolysis-based ATP generation and is pH balanced by increased expressions of acid-loading transporters.Co-expression analyses suggest that lactic acid secretion is regulated by external,non-pH related signals.Overall,our data strongly suggest that the two cell types have the Warburg effect for very different reasons.
基金This work was supported by grants from Georgia Research Alliance, the National Natural Science Foundation of China （61572227）, Projects of international Cooperation and Exchanges of the National Natural Science Foundation of China （81320108025）, and Jilin University.
基金supported by the National Natural Science Foundation(61102162,61271448,31260274,31260219)the Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region(NJYT-14-B10)the Inner Mongolia Science&Technology Plan(20140401)
文摘While some pseudogenes have been reported to play important roles in gene regulation, little is known about the possible relationship between pseudogene functions and evolutionary process of pseudogenes, or about the forces responsible for the pseudogene evolution. In this study, we characterized human processed pseudogenes in terms of evolutionary dynamics. Our results show that pseudogenes tend to evolve toward: lower GC content, strong dinucleotide bias, reduced abundance of transcription factor binding motifs and short palindromes, and decreased ability to form nucleosomes. We explored possible evolutionary forces that shaped the evolution pattern of pseudogenes, and concluded that mutations in pseudogenes are likely determined, at least partially, by neighbor-dependent mutational bias and recombination-associated selection.
基金This work is supported by Georgia Research Alliance,USA and the Technology Development Plan Project of Shandong Province,China(Grant No.2014GSF1181).
文摘Lactates play key roles in facilitating or protecting the development of a cancer in most cancer types.While its beneficial effects to cancer development have been extensively studied,very little is known about what derives the high-level production of lactates in a cancer throughout its entire development.Here we present a novel computational analysis of transcriptomic data of nine primary cancer types,plus a few precancerous and metastatic cancer,to address this issue.Our approach is to identify stress types,which are known to play key roles in cancer development and show strong co-expressions with lactate dehydrogenase-A(LDHA),at different stages of cancer development.A number of interesting observations are made through our analyses,including(i)all nine primary cancer types show similar association patterns between stresses and LDHA,namely the strengths of the associations increase from early-to intermediate-stage cancer tissues but then make a substantial down turn at the most advanced stage;(ii)while the detailed stress types associated with LDHA may vary across different cancer types,stresses induced by apoptosis and adaptive immune responses are present universally,suggesting that these two stresses are possibly two key drivers to keep the high-level production of lactates;and(iii)there is a clear distinction between stress types associated with LDHA in precancerous tissues vs.cancer and metastasis tissues.We anticipate that the analyses can provide highly useful information for designing personalized treatments for different cancers at different stages,as stopping lactate production could have devastating effects on a cancer development.
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.
