{"doi":"10.3389/fgene.2021.737741","title":"Whole Blood Transcriptome Analysis in Children with Sickle Cell Anemia","abstract":"Whole transcriptome RNA-sequencing was performed to quantify RNA expression changes in whole blood samples collected from steady state sickle cell anemia (SCA) and control subjects. Pediatric SCA and control subjects were recruited from Atlanta (GA)—based hospital(s) systems and consented for RNA sequencing. RNA sequencing was performed on an Ion Torrent S5 sequencer, using the Ion Total RNA-seq v2 protocol. Data were aligned to the hg19 reference genome and analyzed in the Partek Genomics studio package (v7.0). 223 genes were differentially expressed between SCA and controls (± 1.5 fold change FDR p < 0.001) and 441 genes show differential transcript expression (± 1.5 fold FDR p < 0.001). Differentially expressed RNA are enriched for hemoglobin associated genes and ubiquitin-proteasome pathway genes. Further analysis shows higher gamma globin gene expression in SCA (33-fold HBG1 and 49-fold HBG2, both FDR p < 0.05), which did not correlate with hemoglobin F protein levels. eQTL analysis identified SNPs in novel non-coding RNA RYR2 gene as having a potential regulatory role in HBG1 and HBG2 expression levels. Gene expression correlation identified JHDM1D-AS1(KDM7A-DT), a non-coding RNA associated with angiogenesis, enhanced GATA1 and decreased JAK-STAT signaling to correlate with HBG1 and HBG2 mRNA levels. These data suggest novel regulatory mechanisms for fetal hemoglobin regulation, which may offer innovative therapeutic approaches for SCA.","journal":"Frontiers in Genetics","year":2022,"id":280090,"datarank":0.540322780310629,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.14446418086834004,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.14446418086834004,"corpus_percentile":64.03651272530362,"corpus_rank":4650,"citation_count":13,"citer_count":12,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6475,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":62.5,"fair_percentile":81.0149801284011,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":637625,"name":"Andrea Pearson","orcid":null,"position":1,"is_corresponding":false},{"id":782203,"name":"Iris Buchanan-Perry","orcid":null,"position":2,"is_corresponding":false},{"id":954134,"name":"Roger P. Simon","orcid":"0000-0001-7287-6915","position":3,"is_corresponding":false},{"id":471010,"name":"David R. Archer","orcid":"0000-0002-9185-0865","position":4,"is_corresponding":false},{"id":229076,"name":"Robert Meller","orcid":"0000-0003-3528-8019","position":5,"is_corresponding":false},{"id":732888,"name":"Beatrice E. Gee","orcid":"0000-0003-0233-0321","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T00:28:59.341002Z","pmid":"35095995","pmcid":"PMC8793691","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":83.3333,"fair_a":81.25,"fair_i":20.0,"fair_r":33.3333,"fair_zscore":1.1103,"fair_rationale":{"fair_score":62.5,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":83.33,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"phs002687.v1.p1","grounded":true,"rationale":"The paper gives a dbGAP accession (phs002687.v1.p1), which is a persistent identifier scheme.","anchors":["RDA-F1-01D — FAIR Data Maturity Model: 'Data is identified by a persistent identifier' (priorit","RDA-F1-02D — FAIR Data Maturity Model: 'Data is identified by a globally unique identifier'","FsF-F1-02D — F-UJI/FAIRsFAIR: 'Data is assigned a persistent identifier'"],"scored":true,"signal":null},{"key":"f_repository_named","label":"Named repository","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"dbGAP","grounded":true,"rationale":"The paper names dbGAP as the repository holding the data.","anchors":["RDA-F4-01M — FAIR Data Maturity Model: metadata is offered so it can be harvested and indexed (","NIH DMS Policy Element 4 (NOT-OD-21-014) — name the repository where data will be archived","NSTC Desirable Characteristics of Data Repositories (2022) — 'Long-Term Sustainability', 'Reten"],"scored":true,"signal":null},{"key":"f_data_availability_statement","label":"Data-availability statement","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"Data are available at dbGAP, Accession: phs002687.v1.p1 ( http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs002687.v1.p1 ). 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