First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target Genes
<p dir="ltr">In 2019, we confirmed that the haploinsufficiency of CHD8 does indeed cause the novel syndromic neurodevelopmental disease we first discovered a dozen years before. Here, we report the first whole transcriptome RNAseq gene expression profiling for a patient with this new...
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2020
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| _version_ | 1864513505653161984 |
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| author | Heba Yasin (14152542) |
| author2 | Robert Stowe (19653565) Chi Kin Wong (3842545) Puthen Veettil Jithesh (12040358) Farah R Zahir (19653568) |
| author2_role | author author author author |
| author_facet | Heba Yasin (14152542) Robert Stowe (19653565) Chi Kin Wong (3842545) Puthen Veettil Jithesh (12040358) Farah R Zahir (19653568) |
| author_role | author |
| dc.creator.none.fl_str_mv | Heba Yasin (14152542) Robert Stowe (19653565) Chi Kin Wong (3842545) Puthen Veettil Jithesh (12040358) Farah R Zahir (19653568) |
| dc.date.none.fl_str_mv | 2020-11-19T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.7759/cureus.11571 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/First_Whole_Transcriptome_RNAseq_on_CHD8_Haploinsufficient_Patient_and_Meta-Analyses_Across_Cellular_Models_Uncovers_Likely_Key_Pathophysiological_Target_Genes/27003466 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Neurosciences Paediatrics chd8 intellectual disability neurodevelopmental disorders autism spectrum disorder rnaseq |
| dc.title.none.fl_str_mv | First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target Genes |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">In 2019, we confirmed that the haploinsufficiency of CHD8 does indeed cause the novel syndromic neurodevelopmental disease we first discovered a dozen years before. Here, we report the first whole transcriptome RNAseq gene expression profiling for a patient with this new syndrome, as a preliminary exploration of potential pathophysiological mechanisms. We compared our patient transcriptome profile with that of all publicly available RNAseq datasets from human cellular models including neuronal progenitor cells, neurons and organoids. We compared differential gene expression profiles overall and conducted phenotype-informed data filtration based on the characteristic syndrome presentation. We found that concordance among differential gene expression profiles was poor across all datasets. Nevertheless, remarkably, we show that the patient blood differential gene expression profile most resembled that of the neuronal cell model, a finding that encourages further transcriptome profiling using patient blood samples. In addition, our custom phenotype-informed analyses yielded important, differentially expressed syndrome pathophysiology target genes. Finally, we note that genes dysregulated due to CHD8 heterozygous deletion are linked to known neurological as well as oncological pathways.</p><h2>Other Information</h2><p dir="ltr">Published in: Cureus<br>License: <a href="https://creativecommons.org/licenses/by/4.0/deed.en" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.7759/cureus.11571" target="_blank">https://dx.doi.org/10.7759/cureus.11571</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_1e7cd3a94c35a06b0d1e966843734442 |
| identifier_str_mv | 10.7759/cureus.11571 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/27003466 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target GenesHeba Yasin (14152542)Robert Stowe (19653565)Chi Kin Wong (3842545)Puthen Veettil Jithesh (12040358)Farah R Zahir (19653568)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesNeurosciencesPaediatricschd8intellectual disabilityneurodevelopmental disordersautism spectrum disorderrnaseq<p dir="ltr">In 2019, we confirmed that the haploinsufficiency of CHD8 does indeed cause the novel syndromic neurodevelopmental disease we first discovered a dozen years before. Here, we report the first whole transcriptome RNAseq gene expression profiling for a patient with this new syndrome, as a preliminary exploration of potential pathophysiological mechanisms. We compared our patient transcriptome profile with that of all publicly available RNAseq datasets from human cellular models including neuronal progenitor cells, neurons and organoids. We compared differential gene expression profiles overall and conducted phenotype-informed data filtration based on the characteristic syndrome presentation. We found that concordance among differential gene expression profiles was poor across all datasets. Nevertheless, remarkably, we show that the patient blood differential gene expression profile most resembled that of the neuronal cell model, a finding that encourages further transcriptome profiling using patient blood samples. In addition, our custom phenotype-informed analyses yielded important, differentially expressed syndrome pathophysiology target genes. Finally, we note that genes dysregulated due to CHD8 heterozygous deletion are linked to known neurological as well as oncological pathways.</p><h2>Other Information</h2><p dir="ltr">Published in: Cureus<br>License: <a href="https://creativecommons.org/licenses/by/4.0/deed.en" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.7759/cureus.11571" target="_blank">https://dx.doi.org/10.7759/cureus.11571</a></p>2020-11-19T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.7759/cureus.11571https://figshare.com/articles/journal_contribution/First_Whole_Transcriptome_RNAseq_on_CHD8_Haploinsufficient_Patient_and_Meta-Analyses_Across_Cellular_Models_Uncovers_Likely_Key_Pathophysiological_Target_Genes/27003466CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/270034662020-11-19T09:00:00Z |
| spellingShingle | First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target Genes Heba Yasin (14152542) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Neurosciences Paediatrics chd8 intellectual disability neurodevelopmental disorders autism spectrum disorder rnaseq |
| status_str | publishedVersion |
| title | First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target Genes |
| title_full | First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target Genes |
| title_fullStr | First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target Genes |
| title_full_unstemmed | First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target Genes |
| title_short | First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target Genes |
| title_sort | First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target Genes |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Neurosciences Paediatrics chd8 intellectual disability neurodevelopmental disorders autism spectrum disorder rnaseq |