Bartha Maria Knoppers’s research while affiliated with University of Helsinki and other places

... We ran the SIGNAL webtool (https://signal.mutationalsignatures.com/) (Degasperi et al. 2020) under default parameters to identify the single base substitution (SBS) signatures active in each patient (Alexandrov et al. 2020). As recommended by the authors, SBS fitting was performed using candidate SBS signatures from CRC. ...

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Genomic diversity and BCL9L mutational status in CTC pools predict overall survival in metastatic colorectal cancer

... In clinical practice, differentiating between multiple primary lung cancers and intrapulmonary metastasis is challenging using pathology or morphologic appearance alone, and NGS is now recommended to help definitively differentiate these entities [5,[8][9][10][11][12][13][14][15]. When using genomic results to define multiple primaries versus intrapulmonary metastasis, we observed significantly improved survival in those with genome-defined multiple primaries versus intrapulmonary metastasis. ...

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Repeat Next-Generation Sequencing (15-Gene Panel) in Unifocal, Synchronous, and Metachronous Non-Small-Cell Lung Cancer—A Single-Center Experience

... Characterizing the full spectrum of SVs in human genomes makes it possible to understand the distribution of SVs in different populations [8]. Additionally, SVs have been found to play a critical role in the development of certain diseases, such as cancer [22] and Alzheimer's [36]. SVs are typically referred to any genome sequence altering event, except for deletions or insertions (indels) shorter than 50 bp [32]. ...

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Blackbird: structural variant detection using synthetic and low-coverage long-reads

... RPL39L is a recently evolved ( 1 ) and non-redundant paralog of RPL39L that has just been implicated in the translation of long-lived, sperm cell-specific proteins ( 11 ). However, the RPL39L mRNA was also observed outside of the germ cell lineage, particularly in ovarian ( 12 ) and breast cancer tissues ( 2 ), as well as in lung cancer ( 13 ) and neuroblastoma ( 11 ) cell lines, where the expression appears to be driven by gene amplifications ( 14 ) and CpG island hypomethylation ( 13 ). These observations suggest that RPL39L's function extends beyond the translation of long-lived sperm cell proteins. ...

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Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding of a subset of proteins with alpha helical domains

... 16 Second, we highlight an association between higher risk of COVID-19 and an ultra-rare missense variant in ZC3HAV1 (rs769102632:A, MAF ¼ 0.002%; p ¼ 3EÀ8; OR ¼ 26.7; 95% CI 8.37-85.38; Figure S1), a gene that encodes a zinc finger antiviral protein 19,20 that inhibits SARS-CoV-2 replication, 21 potentially by upregulating type I interferon responses. 22 Given the potential significance of this finding, we attempted to replicate the ZC3HAV1 rs769102632:A association in an additional 6,223 individuals with COVID-19 with exome or whole-genome sequence data generated as part of the GenOMICC (n ¼ 4,851), 11 Columbia University COVID-19 Biobank (n ¼ 1,152), and Biobanque Quebec (n ¼ 220) 23 studies. We found no carriers for this variant in these additional COVID-19 cases (Table S5) when we expected about four given the observed allele frequency in cases in our study (three and one carriers expected in individuals of African and European ancestry, respectively). ...

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Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals

... We also re-estimated and leveraged the genetic correlation between the traits to amplify statistical power to discover IPF associations by performing multi-trait meta-analysis (MTAG) 24 . For these analyses we used the IPF meta-analysis statistics produced in this study and the latest meta-analysis summaries (Freeze 7) from the COVID-19 Host Genetics Initiative (HGI), for the Hospitalised covid vs. population phenotype (B2_ALL_leave_23andme), as this has produced the best balance between a carefully curated phenotype for severity and statistical power 15,25 (Supplementary Table 15). ...

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Common and rare variant analyses reveal novel genetic factors underlying Idiopathic Pulmonary Fibrosis and shared aetiology with COVID-19

... Genomic alterations have been ranked based on their recurrence and on their functional consequences, finally developing a clustering methodology to discriminate between potential driver events [46]. The extension of the sequencing to intergenic regions allowed evaluation of the burden of putative driver mutations in noncoding regions: on the pan-cancer database, 13% of all mutations were represented by driver point-mutation events in an intergenic region, with 25% of all PCAWG cancers analysed bearing at least one, one-third of which occurred in the TERT promoter, confirming its role in cancer [73][74][75][76][77][78][79]. On the counterpart, 91% of all cancers harboured a somatic driver event in a coding region of a gene (Fig. 3). ...

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Global mapping of cancers: The Cancer Genome Atlas and beyond

... Tumor hypoxia is a common feature of the microenvironment in solid tumors [67,68], primarily resulting from an imbalance between poor vascularization and high oxygen consumption by tumor cells [69]. Hypoxia induces a tumor-adapted phenotype, altering signaling, gene expression, and metabolism [70]. ...

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Myriad factors and pathways influencing tumor radiotherapy resistance

... 39 For pathway enrichments, we aggregated consistently curated FlyBase-associated genesets using the modEnrichr project. 40 We then used the ActivePathways gene set enrichment tool 41 Processing single-cell RNA sequencing data and cell-type-specific differential gene expression analysis ...

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Transcriptomic effects of the foraging gene shed light on pathways of pleiotropy and plasticity

... LncRNAs are involved in multiple developmental processes, including the regulation of Hox genes (Rinn et al. 2007), the regulation of chromatin accessibility in dosage compensation mechanisms (Loda and Heard 2019), and the development of organs such as the brain (Bernard et al. 2010) and heart (Klattenhoff et al. 2013). Alterations in the expression of lncRNAs have also been described for several diseases, including cancer (Huarte 2015;Carlevaro-Fita et al. 2020), cardiovascular diseases (Poller et al. 2018) and neurological disorders (Sunwoo et al. 2017). In fact, the public database LncRNADisease v2.0 currently describes more than 1,700 experimentally validated lncRNA-disease associations (Bao et al. 2019), highlighting lncRNAs as potential tools to understand the mechanisms and prognosis of multiple diseases. ...

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Expression dynamics of long non-coding RNAs during imaginal disc development and regeneration in Drosophila