Detecting haplotype-specific transcript variation in long reads with FLAIR2 Article Swipe
Alison D. Tang
,
Colette Felton
,
Eva Hrabeta‐Robinson
,
Roger Volden
,
Christopher Vollmers
,
Angela N. Brooks
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1186/s13059-024-03301-y
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1186/s13059-024-03301-y
Background RNA-seq has brought forth significant discoveries regarding aberrations in RNA processing, implicating these RNA variants in a variety of diseases. Aberrant splicing and single nucleotide variants (SNVs) in RNA have been demonstrated to alter transcript stability, localization, and function. In particular, the upregulation of ADAR, an enzyme that mediates adenosine-to-inosine editing, has been previously linked to an increase in the invasiveness of lung adenocarcinoma cells and associated with splicing regulation. Despite the functional importance of studying splicing and SNVs, the use of short-read RNA-seq has limited the community’s ability to interrogate both forms of RNA variation simultaneously. Results We employ long-read sequencing technology to obtain full-length transcript sequences, elucidating cis-effects of variants on splicing changes at a single molecule level. We develop a computational workflow that augments FLAIR, a tool that calls isoform models expressed in long-read data, to integrate RNA variant calls with the associated isoforms that bear them. We generate nanopore data with high sequence accuracy from H1975 lung adenocarcinoma cells with and without knockdown of ADAR . We apply our workflow to identify key inosine isoform associations to help clarify the prominence of ADAR in tumorigenesis. Conclusions Ultimately, we find that a long-read approach provides valuable insight toward characterizing the relationship between RNA variants and splicing patterns.
Related Topics
Concepts
ADAR
Biology
RNA editing
RNA splicing
RNA
Alternative splicing
Computational biology
Genetics
Transcriptome
Gene isoform
RNA-Seq
Gene
Gene expression
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1186/s13059-024-03301-y
- https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-024-03301-y
- OA Status
- gold
- Cited By
- 9
- References
- 84
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4400248480
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4400248480Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1186/s13059-024-03301-yDigital Object Identifier
- Title
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Detecting haplotype-specific transcript variation in long reads with FLAIR2Work title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
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2024-07-02Full publication date if available
- Authors
-
Alison D. Tang, Colette Felton, Eva Hrabeta‐Robinson, Roger Volden, Christopher Vollmers, Angela N. BrooksList of authors in order
- Landing page
-
https://doi.org/10.1186/s13059-024-03301-yPublisher landing page
- PDF URL
-
https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-024-03301-yDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-024-03301-yDirect OA link when available
- Concepts
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ADAR, Biology, RNA editing, RNA splicing, RNA, Alternative splicing, Computational biology, Genetics, Transcriptome, Gene isoform, RNA-Seq, Gene, Gene expressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
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9Total citation count in OpenAlex
- Citations by year (recent)
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2025: 7, 2024: 1, 2023: 1Per-year citation counts (last 5 years)
- References (count)
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84Number of works referenced by this work
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-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.sequence | 158 |
| abstract_inverted_index.splicing | 23, 70, 78, 115, 210 |
| abstract_inverted_index.studying | 77 |
| abstract_inverted_index.valuable | 200 |
| abstract_inverted_index.variants | 16, 27, 113, 208 |
| abstract_inverted_index.workflow | 126, 175 |
| abstract_inverted_index.diseases. | 21 |
| abstract_inverted_index.expressed | 136 |
| abstract_inverted_index.function. | 40 |
| abstract_inverted_index.integrate | 141 |
| abstract_inverted_index.knockdown | 168 |
| abstract_inverted_index.long-read | 102, 138, 197 |
| abstract_inverted_index.patterns. | 211 |
| abstract_inverted_index.regarding | 8 |
| abstract_inverted_index.variation | 97 |
| abstract_inverted_index.Background | 1 |
| abstract_inverted_index.associated | 68, 147 |
| abstract_inverted_index.functional | 74 |
| abstract_inverted_index.importance | 75 |
| abstract_inverted_index.nucleotide | 26 |
| abstract_inverted_index.previously | 55 |
| abstract_inverted_index.prominence | 186 |
| abstract_inverted_index.sequences, | 109 |
| abstract_inverted_index.sequencing | 103 |
| abstract_inverted_index.short-read | 84 |
| abstract_inverted_index.stability, | 37 |
| abstract_inverted_index.technology | 104 |
| abstract_inverted_index.transcript | 36, 108 |
| abstract_inverted_index.Conclusions | 191 |
| abstract_inverted_index.Ultimately, | 192 |
| abstract_inverted_index.aberrations | 9 |
| abstract_inverted_index.cis-effects | 111 |
| abstract_inverted_index.discoveries | 7 |
| abstract_inverted_index.elucidating | 110 |
| abstract_inverted_index.full-length | 107 |
| abstract_inverted_index.implicating | 13 |
| abstract_inverted_index.interrogate | 92 |
| abstract_inverted_index.particular, | 42 |
| abstract_inverted_index.processing, | 12 |
| abstract_inverted_index.regulation. | 71 |
| abstract_inverted_index.significant | 6 |
| abstract_inverted_index.associations | 181 |
| abstract_inverted_index.demonstrated | 33 |
| abstract_inverted_index.invasiveness | 62 |
| abstract_inverted_index.relationship | 205 |
| abstract_inverted_index.upregulation | 44 |
| abstract_inverted_index.community’s | 89 |
| abstract_inverted_index.computational | 125 |
| abstract_inverted_index.localization, | 38 |
| abstract_inverted_index.adenocarcinoma | 65, 163 |
| abstract_inverted_index.characterizing | 203 |
| abstract_inverted_index.tumorigenesis. | 190 |
| abstract_inverted_index.simultaneously. | 98 |
| abstract_inverted_index.adenosine-to-inosine | 51 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 89 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 6 |
| citation_normalized_percentile.value | 0.8970059 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |