The Experts below are selected from a list of 186 Experts worldwide ranked by ideXlab platform
Paul Franken - One of the best experts on this subject based on the ideXlab platform.
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Recent advances in understanding the Genetics of Sleep.
F1000Research, 2020Co-Authors: Maxime Jan, Bruce F. O'hara, Paul FrankenAbstract:Sleep is a ubiquitous and complex behavior in both its manifestation and regulation. Despite its essential role in maintaining optimal performance, health, and well-being, the genetic mechanisms underlying Sleep remain poorly understood. Here, we review the forward genetic approaches undertaken in the last four years to elucidate the genes and gene pathways affecting Sleep and its regulation. Despite an increasing number of studies and mining large databases, a coherent picture on "Sleep" genes has yet to emerge. We highlight the results achieved by using unbiased genetic screens mainly in humans, mice, and fruit flies with an emphasis on normal Sleep and make reference to lessons learned from the circadian field.
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a multi omics digital research object for the Genetics of Sleep regulation
Scientific Data, 2019Co-Authors: Maxime Jan, Nastassia Gobet, Shanaz Diessler, Paul Franken, Ioannis XenariosAbstract:With the aim to uncover the molecular pathways underlying the regulation of Sleep, we recently assembled an extensive and comprehensive systems Genetics dataset interrogating a genetic reference population of mice at the levels of the genome, the brain and liver transcriptomes, the plasma metabolome, and the Sleep-wake phenome. To facilitate a meaningful and efficient re-use of this public resource by others we designed, describe in detail, and made available a Digital Research Object (DRO), embedding data, documentation, and analytics. We present and discuss both the advantages and limitations of our multi-modal resource and analytic pipeline. The reproducibility of the results was tested by a bioinformatician not implicated in the original project and the robustness of results was assessed by re-annotating genetic and transcriptome data from the mm9 to the mm10 mouse genome assembly.
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a multi omics digital research object for the Genetics of Sleep regulation
bioRxiv, 2019Co-Authors: Maxime Jan, Nastassia Gobet, Shanaz Diessler, Paul Franken, Ioannis XenariosAbstract:Abstract More and more researchers make use of multi-omics approaches to tackle complex cellular and organismal systems. It has become apparent that the potential for re-use and integrate data generated by different labs can enhance knowledge. However, a meaningful and efficient re-use of data generated by others is difficult to achieve without in depth understanding of how these datasets were assembled. We therefore designed and describe in detail a digital research object embedding data, documentation and analytics on mouse Sleep regulation. The aim of this study was to bring together electrophysiological recordings, Sleep-wake behavior, metabolomics, Genetics, and gene regulatory data in a systems Genetics model to investigate Sleep regulation in the BXD panel of recombinant inbred lines. We here showcase both the advantages and limitations of providing such multi-modal data and analytics. The reproducibility of the results was tested by a bioinformatician not implicated in the original project and the robustness of results was assessed by re-annotating genetic and transcriptome data from the mm9 to the mm10 mouse genome assembly.
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A multi-omics digital research object for the Genetics of Sleep regulation: Input-data and code
2019Co-Authors: Maxime Jan, Nastassia Gobet, Shanaz Diessler, Paul Franken, Ioannis XenariosAbstract:Input, Output data and source code for the systems Genetics of Sleep regulation using the mm9 assembly and mm10 assembly.HivePlots_v3.1f_PearsonQuick2.PrecomputedCorrelations.Rdata is an intermediate file for hiveplot visualization using the mm9 assembly.and HivePlots_v3.2_PearsonQuick2.PrecomputedCorrelations.Rdata is an intermediate file for hiveplot visualization using the mm10 assembly.Source Code zip files are backup scripts, description and documentation that are available here: https://gitlab.unil.ch/mjan/Systems_Genetics_of_Sleep_Regulation. Scripts using the mm10 assembly are available as the mm10 branch. Master branch is for the mm9 assembly and our related publication.bxd.vital-it.ch.zip are backup files from the bxd.vital-it.ch website.
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Genetics of Sleep
Annual review of genetics, 2008Co-Authors: Rozi Andretic, Paul Franken, Mehdi TaftiAbstract:Molecular and genetic approaches in several species have provided new insights into the mechanisms of rest-activity and Sleep-wake regulation. Many of these discoveries are believed to support hypotheses about Sleep functions, which nevertheless remain elusive. In this review we discuss the specific contribution of both mammalian and invertebrate models to our understanding of the molecular basis of Sleep.
Mehdi Tafti - One of the best experts on this subject based on the ideXlab platform.
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The Genetics of Sleep
Oxford Medicine Online, 2017Co-Authors: Alexandra Sousek, Mehdi TaftiAbstract:Although there is strong evidence for a genetic contribution to inter-individual variations in Sleep, the underlying factors and their interaction remain largely elusive. Much effort has been expended in studying genetic variations contributing to circadian and Sleep phenotypes, the individual pattern of the human Sleep EEG, reactions to Sleep loss, and the pathophysiology of Sleep-related disorders. Certain Sleep-related diseases may be caused by single genes, while the etiology of others seems to be variable and complex. This is especially the case when the immune system is involved. This chapter reports on twin and familial studies, genetic variations and mutations affecting neurotransmitters and other signaling pathways and thereby affecting Sleep, and impacts of gene expression processes and the immune system on Sleep. Although much knowledge has been gained, further research is needed to elucidate the all-embracing mechanisms and their interactions that regulate Sleep.
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Genetics of Sleep
Annual review of genetics, 2008Co-Authors: Rozi Andretic, Paul Franken, Mehdi TaftiAbstract:Molecular and genetic approaches in several species have provided new insights into the mechanisms of rest-activity and Sleep-wake regulation. Many of these discoveries are believed to support hypotheses about Sleep functions, which nevertheless remain elusive. In this review we discuss the specific contribution of both mammalian and invertebrate models to our understanding of the molecular basis of Sleep.
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Narcolepsy and familial advanced Sleep-phase syndrome: molecular Genetics of Sleep disorders.
Current opinion in genetics & development, 2007Co-Authors: Mehdi Tafti, Yves Dauvilliers, Sebastiaan OvereemAbstract:Sleep disorders are very prevalent and represent an emerging worldwide epidemic. However, research into the molecular Genetics of Sleep disorders remains surprisingly one of the least active fields. Nevertheless, rapid progress is being made in several prototypical disorders, leading recently to the identification of the molecular pathways underlying narcolepsy and familial advanced Sleep-phase syndrome. Since the first reports of spontaneous and induced loss-of-function mutations leading to hypocretin deficiency in human and animal models of narcolepsy, the role of this novel neurotransmission pathway in Sleep and several other behaviors has gained extensive interest. Also, very recent studies using an animal model of familial advanced Sleep-phase syndrome shed new light on the regulation of circadian rhythms.
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Quantitative Genetics of Sleep in inbred mice.
Dialogues in clinical neuroscience, 2007Co-Authors: Mehdi TaftiAbstract:The timing and the organization of Sleep architecture are mainly controlled by the circadian system, while Sleep need and intensity are regulated by a homeostatic process. How independent these two systems are in regulating Sleep is not well understood. In contrast to the impressive progress in the molecular Genetics of circadian rhythms, little is known about the molecular basis of Sleep. Nevertheless, as summarized here, phenotypic dissection of Sleep into its most basic aspects can be used to identify both the single major genes and small effect quantitative trait loci involved. Although experimental models such as the mouse are more readily amenable to genetic analysis of Sleep, similar approaches can be applied to humans.
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Genetics of Sleep AND Sleep DISORDERS
Frontiers in Bioscience, 2003Co-Authors: Paul Franken, Mehdi TaftiAbstract:Sleep disorders are among the most common health problems encountered in medicine and have important social and economic impacts. New technologies as well as the current progress in genome sequencing projects of different species raise new hopes to understand the molecular basis of Sleep and its disorders. Substantial progress has been achieved in our understanding of the neurobiology underlying the expression and regulation of Sleep, but little is known about the molecular basis of Sleep. In this chapter, we review the various approaches that can be used to identify and isolate Sleep-related genes and then present a general overview of the different Sleep disorders for which a genetic component has been described.
Susan Redline - One of the best experts on this subject based on the ideXlab platform.
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The DSM-v Sleep-wake disorders nosology: an update and an invitation to the Sleep community.
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2010Co-Authors: Charles F. Reynolds, Susan Redline, AdvisorsAbstract:During the period of January 18–March 18, 2010 (approximately), the American Psychiatric Association is planning to post on its website updates of the DSM-V Sleep-wake disorders nosology. The updates will include draft diagnostic criteria, research and clinically based rationales for changes, and proposed dimensional measures of severity. We would like to invite the readers of the Journal of Clinical Sleep Medicine to comment, to offer a rationale and supporting evidence to argue for or against the changes proposed by the DSM-V Sleep-wake disorders workgroup, and to propose additional revisions to the criteria. The workgroup's recommended changes were posted on the website (DSM5.org) on or about January 20, 2010. The overriding goal of the revision has been to enhance the clinical utility, reliability, and validity of the DSM Sleep-wake disorders nosology. The primary users of DSM are mental health and general medical clinicians, not Sleep disorder specialists. Mindful of these users, the workgroup has sought to simplify the classification of Sleep-wake disorders in clinically meaningful ways, to facilitate identification of Sleep disorders, and to offer useful dimensional measures of severity. In refining the diagnostic criteria and expanding the accompanying text, the DSM-V workgroup has also strived to incorporate information that reflects major advances in the basic physiology and Genetics of Sleep conditions, information about lifespan issues, and evidence-based research in treatment outcomes that have occurred in the years since DSM-IV. In this context, we have an abundance of biomarker data (polysomnographic and neurobiologic) generally lacking in other areas of psychiatric diagnosis. Thus, we have an opportunity to model for other areas of psychiatric classification the incorporation of quantitative, physiologic measures into the diagnostic classification system, dimensional measures of severity, and the accompanying text. An important goal of DSM-V Sleep nosology will be to improve recognition of Sleep disorders by mental health and general medical clinicians, to improve appropriate referrals to a Sleep specialist, and to improve the approach to treatment of Sleep disorders that are comorbid with other health conditions. The major changes under consideration include: (1) eliminating the diagnosis of “primary insomnia” in favor of “insomnia disorder”, with concurrent specification of clinically comorbid conditions (both medical and psychiatric). Making this change will allow us also to (2) eliminate “Sleep disorder related to another mental disorder” and “Sleep disorder due to a general medical condition”, in favor of “insomnia disorder” (or “hypersomnia disorder”) with concurrent specification of clinically comorbid conditions. These changes move away from the causal attribution inherent in DSM-IV and simply specify clinically relevant comorbidities. As such they are consistent with the data and recommendations of the 2005 NIH State of the Science position on classification of insomnia disorders. The criteria underscore that the patient has a Sleep disorder (either insomnia or hypersomnia) that warrants independent clinical attention, in addition to mental/psychiatric or medical disorders also present. The workgroup will also propose (3) aggregating hypersomnia disorder and narcolepsy without cataplexy, which will be distinguished from narcolepy/cataplexy/hypocretin-1 deficiency disorder. We will also propose (4) breaking up the unitary DSM-IV “breathing-related Sleep disorder” into distinct syndromes of obstructive versus central forms of Sleep apnea in order to better inform treatment planning. Similar to other workgroups in DSM-V, we will (5) decrease the use of “not otherwise specified” (NOS) as a diagnostic category. This change will encompass elevation of REM Sleep behavior disorder and restless legs syndrome to full-fledged diagnostic status (from their current classification in DSM-IV as “not otherwise specified”). We will argue for (6) aggregation of NREM parasomnias under “confusional arousal disorders” (to include confusional arousal disorder, Sleep walking, and Sleep terrors). Finally, we will propose (7) further elaboration of a greater number of distinct types of circadian rhythm disorders, such as advanced Sleep phase syndrome, which were not in DSM-IV. The secondary analyses performed by the workgroup and our reviews of the literature published since DSM-IV are leading to greater and more specific quantification of some criteria, as well as elaboration of epidemiologic, genetic, neurobiological, and treatment response data in the accompanying text. These data serve as concurrent and prognostic validators of the proposed diagnostic categories. We will continue to provide linkages to ICSD nosology in the text, while recognizing that DSM-V diagnoses are often broader in scope than those in ICSD. “Insomnia disorder” is a good example of this. Finally, we anticipate engaging in field trials to assess the clinical utility and reliability of some of the diagnostic changes proposed, especially related to insomnia disorder. We are working with other DSM-V groups to incorporate simple dimensional measures of Sleep quality into their field trials. We believe that the use of dimensional severity measures is also likely to reveal subthreshold or subdiagnostic conditions in some patients at risk for developing full-fledged, syndromal Sleep disorders. Such patients may be candidates for preventive interventions. Many of these recommendations resulted from long hours of careful deliberation. Compromise was sometimes needed to strike the appropriate balance between scientific precision and clinical utility. At other times, the evidence base was relatively weak and required expert opinion. For these reasons, the workgroup recognizes that some stakeholders will have different, valid perspectives about the proposed changes. The process of revision of the DSM-V has been intended to be transparent and inclusive. For these reasons the Sleep community's input is sincerely sought and will be considered before finalizing the recommendations.
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The DSM-V Sleep-Wake Disorders Nosology: An Update and an Invitation to the Sleep Community
Sleep, 2010Co-Authors: Charles F. Reynolds, Susan RedlineAbstract:DURING THE PERIOD of JANUARY 18–MARCH 18, 2010 (APPROXIMATELY), THE AMERICAN PSYCHIATRIC ASSOCIATION IS PLANNING TO POST ON ITS website updates of the DSM-V Sleep-wake disorders nosology. The updates will include draft diagnostic criteria, research and clinically based rationales for changes, and proposed dimensional measures of severity. We would like to invite the readers of Sleep to comment, to offer a rationale and supporting evidence to argue for or against the changes proposed by the DSM-V Sleep-wake disorders workgroup, and to propose additional revisions to the criteria. The workgroup's recommended changes will be posted on the website (DSM5.org) on or about January 18, 2010. The overriding goal of the revision has been to enhance the clinical utility, reliability, and validity of the DSM Sleep-wake disorders nosology. The primary users of DSM are mental health and general medical clinicians, not Sleep disorder specialists. Mindful of these users, the workgroup has sought to simplify the classification of Sleep-wake disorders in clinically meaningful ways, to facilitate identification of Sleep disorders, and to offer useful dimensional measures of severity. In refining the diagnostic criteria and expanding the accompanying text, the DSM-V workgroup has also strived to incorporate information that reflects major advances in the basic physiology and Genetics of Sleep conditions, information about lifespan issues, and evidence-based research in treatment outcomes that have occurred in the years since DSM-IV. In this context, we have an abundance of biomarker data (polysomnographic and neurobiologic) generally lacking in other areas of psychiatric diagnosis. Thus, we have an opportunity to model for other areas of psychiatric classification the incorporation of quantitative, physiologic measures into the diagnostic classification system, dimensional measures of severity, and the accompanying text. An important goal of DSM-V Sleep nosology will be to improve recognition of Sleep disorders by mental health and general medical clinicians, to improve appropriate referrals to a Sleep specialist, and to improve the approach to treatment of Sleep disorders that are comorbid with other health conditions. The major changes under consideration include: (1) eliminating the diagnosis of “primary insomnia” in favor of “insomnia disorder,” with concurrent specification of clinically comorbid conditions (both medical and psychiatric). Making this change will allow us also to (2) eliminate “Sleep disorder related to another mental disorder” and “Sleep disorder due to a general medical condition,” in favor of “insomnia disorder” (or “hypersomnia disorder”) with concurrent specification of clinically comorbid conditions. These changes move away from the causal attribution inherent in DSM-IV and simply specify clinically relevant comorbidities. As such they are consistent with the data and recommendations of the 2005 NIH State of the Science position on classification of insomnia disorders. The criteria underscore that the patient has a Sleep disorder (either insomnia or hypersomnia) that warrants independent clinical attention, in addition to mental/psychiatric or medical disorders also present. The workgroup will also propose (3) aggregating hypersomnia disorder and narcolepsy without cataplexy, which will be distinguished from narcolepy/cataplexy/hypocretin-1 deficiency disorder. We will also propose (4) breaking up the unitary DSM-IV “breathing-related Sleep disorder” into distinct syndromes of obstructive versus central forms of Sleep apnea in order to better inform treatment planning. Similar to other workgroups in DSM-V, we will (5) decrease the use of “not otherwise specified” (NOS) as a diagnostic category. This change will encompass elevation of REM Sleep behavior disorder and restless legs syndrome to full-fledged diagnostic status (from their current classification in DSM-IV as “not otherwise specified”). We will argue for (6) aggregation of NREM parasomnias under “confusional arousal disorders” (to include confusional arousal disorder, Sleep walking, and Sleep terrors). Finally, we will propose (7) further elaboration of a greater number of distinct types of circadian rhythm disorders, such as advanced Sleep phase syndrome, which were not in DSM-IV. The secondary analyses performed by the workgroup and our reviews of the literature published since DSM-IV are leading to greater and more specific quantification of some criteria, as well as elaboration of epidemiologic, genetic, neurobiological, and treatment response data in the accompanying text. These data serve as concurrent and prognostic validators of the proposed diagnostic categories. We will continue to provide linkages to ICSD nosology in the text, while recognizing that DSM-V diagnoses are often broader in scope than those in ICSD. “Insomnia disorder” is a good example of this. Finally, we anticipate engaging in field trials to assess the clinical utility and reliability of some of the diagnostic changes proposed, especially related to insomnia disorder. We are working with other DSM-V groups to incorporate simple dimensional measures of Sleep quality into their field trials. We believe that the use of dimensional severity measures is also likely to reveal subthreshold or subdiagnostic conditions in some patients at risk for developing full-fledged, syndromal Sleep disorders. Such patients may be candidates for preventive interventions. Many of these recommendations resulted from long hours of careful deliberation. Compromise was sometimes needed to strike the appropriate balance between scientific precision and clinical utility. At other times, the evidence base was relatively weak and required expert opinion. For these reasons, the workgroup recognizes that some stakeholders will have different, valid perspectives about the proposed changes. The process of revision of the DSM-V has been intended to be transparent and inclusive. For these reasons the Sleep community's input is sincerely sought and will be considered before finalizing the recommendations.
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Sleep apnea Genetics of Sleep apnea
Encyclopedia of Respiratory Medicine, 2006Co-Authors: Sanjay R. Patel, Susan RedlineAbstract:Obstructive Sleep apnea is a disorder that has a clear genetic component. A familial basis for the disorder is evidenced by the substantially increased risk for snoring or Sleep apnea among relatives of affected individuals. Approximately one-third of the population variance in apnea severity, as measured by the apnea/hypopnea index, is explained by familial clustering. The pathways by which genetic predisposition may influence the development of Sleep apnea are multiple. Obesity, craniofacial anatomy, and ventilatory control are all traits that are highly heritable, and each influences the risk of apnea development. The Genetics of obesity has been most well studied, with dozens of candidate genes proposed to influence a person's weight. Data suggest that these obesity-defining loci explain only half of the genetic variance in Sleep apnea. Thus, other mechanisms are also important. Work is under way to identify risk genes for Sleep apnea, and several candidates such as APOE have emerged. Research has also begun to identify genetic loci that may modulate the physiologic effect of Sleep apnea on the development of secondary disorders, such as Sleepiness, hypertension, and cardiac disease.
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Sleep APNEA | Genetics of Sleep Apnea
Encyclopedia of Respiratory Medicine, 2006Co-Authors: Sanjay R. Patel, Susan RedlineAbstract:Obstructive Sleep apnea is a disorder that has a clear genetic component. A familial basis for the disorder is evidenced by the substantially increased risk for snoring or Sleep apnea among relatives of affected individuals. Approximately one-third of the population variance in apnea severity, as measured by the apnea/hypopnea index, is explained by familial clustering. The pathways by which genetic predisposition may influence the development of Sleep apnea are multiple. Obesity, craniofacial anatomy, and ventilatory control are all traits that are highly heritable, and each influences the risk of apnea development. The Genetics of obesity has been most well studied, with dozens of candidate genes proposed to influence a person's weight. Data suggest that these obesity-defining loci explain only half of the genetic variance in Sleep apnea. Thus, other mechanisms are also important. Work is under way to identify risk genes for Sleep apnea, and several candidates such as APOE have emerged. Research has also begun to identify genetic loci that may modulate the physiologic effect of Sleep apnea on the development of secondary disorders, such as Sleepiness, hypertension, and cardiac disease.
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The Genetics of Sleep apnea
Sleep medicine reviews, 2000Co-Authors: Susan Redline, Peter V. TishlerAbstract:Obstructive Sleep apnea hypopnea syndrome (OSAHS) is a complex chronic condition that is undoubtedly influenced by multiple factors. Accumulating data suggest that there are strong genetic underpinnings for this condition. It has been estimated that approximately 40% of the variance in the apnea hypopnea index (AHI) may be explained by familial factors. It is likely that genetic factors associated with craniofacial structure, body fat distribution and neural control of the upper airway muscles interact to produce the OSAHS phenotype. Although the role of specific genes that influence the development of OSAHS have not yet been identified, current research in rodents suggests that several genetic systems may be important. In this chapter, we shall first define the OSAHS phenotype, and then review the evidence that suggests an underlying genetic basis of OSAHS, the risk factors for OSAHS that may be inherited, and potential candidate genes.
Allan I. Pack - One of the best experts on this subject based on the ideXlab platform.
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Genetics of Sleep Disorders.
The Psychiatric clinics of North America, 2015Co-Authors: Philip R. Gehrman, Brendan T. Keenan, Enda M. Byrne, Allan I. PackAbstract:Sleep disorders are, in part, attributable to genetic variability across individuals. There has been considerable progress in understanding the role of genes for some Sleep disorders, such as the identification of a human leukocyte antigen gene for narcolepsy. For other Sleep disorders, such as insomnia, little work has been done. Optimizing phenotyping strategies is critical, as is the case for Sleep apnea, for which intermediate traits such as obesity and craniofacial features may prove to be more tractable for genetic studies. Rapid advances in genotyping and statistical Genetics are likely to lead to greater discoveries in the near future.
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Genetics of Sleep and Its Disorders
Sleep Medicine Clinics, 2011Co-Authors: Allan I. PackAbstract:cl in ic s. co m In this issue there are reviews of many aspects of the Genetics of Sleep and its disorders. As the reviews point out, there are major opportunities for genetic research. Many aspects of normal Sleep are heritable—Sleep duration, timing of Sleep, response to Sleepdeprivation,ECGcharacteristics. Moreover, many of the common Sleep disorders such as insomnia, parasomnias, circadian rhythm disorders, restless legs syndrome, narcolepsy, and obstructive Sleep apnea are heritable. Thus, there are many, many opportunities for genetic research.Moreover, as described throughout these reviews, therehavebeendramatic improvements in the technological approaches available for genotyping and continued development of these technologies. Another major advantage for studies of the Genetics of Sleep and its disorders is that over the last decade, a Sleep-like state has been identified in model systems, in particular, Drosophila, zebra fish, and Caenorhabditis elegans (for discussion of these, see Raizen and Zimmerman). This complements studies in rodent models described by Summa and Turek. Thus, Sleep research is ideally positioned to first identify genes responsible for particular aspects of the phenotype in model systems and transfer findings to human studies. Identification of clock genes in Drosophila andmice with subsequent identification of variants of these genes leading to circadian rhythm disorders is a good example of this (see Chang and Zee). But the reverse is also possible, ie, identifying mutants in human studies and then assessing their functional significance by expressing these human mutations in model systems. The
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Genetics of Sleep Apnea
Sleep Medicine Clinics, 2011Co-Authors: Allan I. PackAbstract:Obstructive Sleep apnea (OSA) is a common disorder with multiple adverse consequences. This disorder leads to excessive Sleepiness, with increased risk of motor vehicle crashes, and is an independent risk factor for cardiovascular disease and insulin resistance. However, not all patients with OSA get all these consequences. There is a differential susceptibility to these consequences. Even patientswith severeOSAmaynot complain of excessive Sleepiness. It is likely that this differential susceptibility is in part genetic, which complicates identifying genes conferring risk for OSA because patients with consequences, such as excessive Sleepiness, are more likely to present clinically. In this article, the evidence that there is a genetic contribution to OSA is reviewed. The likely intermediate traits are discussed, each of which may have genetic contributions. The studies identifying gene variants conferring risk for OSA are described. The studies of the genetic determinants of cardiovascular consequences of OSA are also described in the contribution by Ryan and colleagues in this issue. At present, there are no firmly established gene variants conferring risk for OSA, which have been replicated in several studies. In all genetic studies, replication is the key and adds confidence to the findings.
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Molecular Mechanisms of Sleep and Wakefulness
Annals of the New York Academy of Sciences, 2008Co-Authors: Miroslaw Mackiewicz, Nirinjini Naidoo, John E. Zimmerman, Allan I. PackAbstract:Major questions on the biology of Sleep include the following: what are the molecular functions of Sleep; why can wakefulness only be sustained for defined periods before there is behavioral impairment; what genes contribute to the individual differences in Sleep and the response to Sleep deprivation? Behavioral criteria to define Sleep have facilitated identification of Sleep states in a number of different model systems: Drosophila, zebrafish, and Caenorhabditis elegans. Each system has unique strengths. Studies in these model systems are identifying conserved signaling mechanisms regulating Sleep that are present in mammals. For example, the PKA-CREB signaling mechanism promotes wakefulness in Drosophila, mice, and C. elegans. Microarray studies indicate that genes whose expression is upregulated during Sleep are involved in macromolecule biosynthesis (proteins, lipids [including cholesterol], heme). Thus, a key function of Sleep is likely to be macromolecule synthesis. Moreover, in all species studied to date, there is upregulation of the molecular chaperone BiP with extended wakefulness. Sleep deprivation leads to cellular ER stress in brain and the unfolded protein response. Identification of genes regulating Sleep has the potential for translational studies to elucidate the Genetics of Sleep and response to Sleep deprivation in humans.
Ioannis Xenarios - One of the best experts on this subject based on the ideXlab platform.
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a multi omics digital research object for the Genetics of Sleep regulation
Scientific Data, 2019Co-Authors: Maxime Jan, Nastassia Gobet, Shanaz Diessler, Paul Franken, Ioannis XenariosAbstract:With the aim to uncover the molecular pathways underlying the regulation of Sleep, we recently assembled an extensive and comprehensive systems Genetics dataset interrogating a genetic reference population of mice at the levels of the genome, the brain and liver transcriptomes, the plasma metabolome, and the Sleep-wake phenome. To facilitate a meaningful and efficient re-use of this public resource by others we designed, describe in detail, and made available a Digital Research Object (DRO), embedding data, documentation, and analytics. We present and discuss both the advantages and limitations of our multi-modal resource and analytic pipeline. The reproducibility of the results was tested by a bioinformatician not implicated in the original project and the robustness of results was assessed by re-annotating genetic and transcriptome data from the mm9 to the mm10 mouse genome assembly.
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a multi omics digital research object for the Genetics of Sleep regulation
bioRxiv, 2019Co-Authors: Maxime Jan, Nastassia Gobet, Shanaz Diessler, Paul Franken, Ioannis XenariosAbstract:Abstract More and more researchers make use of multi-omics approaches to tackle complex cellular and organismal systems. It has become apparent that the potential for re-use and integrate data generated by different labs can enhance knowledge. However, a meaningful and efficient re-use of data generated by others is difficult to achieve without in depth understanding of how these datasets were assembled. We therefore designed and describe in detail a digital research object embedding data, documentation and analytics on mouse Sleep regulation. The aim of this study was to bring together electrophysiological recordings, Sleep-wake behavior, metabolomics, Genetics, and gene regulatory data in a systems Genetics model to investigate Sleep regulation in the BXD panel of recombinant inbred lines. We here showcase both the advantages and limitations of providing such multi-modal data and analytics. The reproducibility of the results was tested by a bioinformatician not implicated in the original project and the robustness of results was assessed by re-annotating genetic and transcriptome data from the mm9 to the mm10 mouse genome assembly.
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A multi-omics digital research object for the Genetics of Sleep regulation: Input-data and code
2019Co-Authors: Maxime Jan, Nastassia Gobet, Shanaz Diessler, Paul Franken, Ioannis XenariosAbstract:Input, Output data and source code for the systems Genetics of Sleep regulation using the mm9 assembly and mm10 assembly.HivePlots_v3.1f_PearsonQuick2.PrecomputedCorrelations.Rdata is an intermediate file for hiveplot visualization using the mm9 assembly.and HivePlots_v3.2_PearsonQuick2.PrecomputedCorrelations.Rdata is an intermediate file for hiveplot visualization using the mm10 assembly.Source Code zip files are backup scripts, description and documentation that are available here: https://gitlab.unil.ch/mjan/Systems_Genetics_of_Sleep_Regulation. Scripts using the mm10 assembly are available as the mm10 branch. Master branch is for the mm9 assembly and our related publication.bxd.vital-it.ch.zip are backup files from the bxd.vital-it.ch website.