Romero, J.P. (Juan Pablo)

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2018 - 20202

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    Comparison of RNA-seq and microarray platforms for splice event detection using a cross-platform algorithm
    (BioMed Central, 2018) Romero, J.P. (Juan Pablo); Pio, R. (Rubén); Ortiz-Estévez, M. (Maria); Loos, R. (Remco); Muniategui, A. (Ander); Carrancio, S. (Soraya); Carazo-Melo, F.(Fernando); Montuenga-Badia, L.M. (Luis M.); Miguel, F.J. (Fernando J.) de; Trotter, M. (Matthew); Rubio, A. (Ángel)
    Background: RNA-seq is a reference technology for determining alternative splicing at genome-wide level. Exon arrays remain widely used for the analysis of gene expression, but show poor validation rate with regard to splicing events. Commercial arrays that include probes within exon junctions have been developed in order to overcome this problem. We compare the performance of RNA-seq (Illumina HiSeq) and junction arrays (Affymetrix Human Transcriptome array) for the analysis of transcript splicing events. Three different breast cancer cell lines were treated with CX-4945, a drug that severely affects splicing. To enable a direct comparison of the two platforms, we adapted EventPointer, an algorithm that detects and labels alternative splicing events using junction arrays, to work also on RNA-seq data. Common results and discrepancies between the technologies were validated and/or resolved by over 200 PCR experiments. Results: As might be expected, RNA-seq appears superior in cases where the technologies disagree and is able to discover novel splicing events beyond the limitations of physical probe-sets. We observe a high degree of coherence between the two technologies, however, with correlation of EventPointer results over 0.90. Through decimation, the detection power of the junction arrays is equivalent to RNA-seq with up to 60 million reads. Conclusions: Our results suggest, therefore, that exon-junction arrays are a viable alternative to RNA-seq for detection of alternative splicing events when focusing on well-described transcriptional regions.
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    Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2
    (2020) Penninger, J.M. (Josef M.); Hagelkrüys, A. (Astrid); Garreta, E. (Elena); Romero, J.P. (Juan Pablo); Montserrat, N. (Nuria); Hurtado-del-Pozo, C. (Carmen); Leopoldi, A. (Alexandra); Wimmer, R.A. (Reiner A.); Stahl, M. (Martin); Conder, R. (Ryan); Wirnsberger, G. (Gerald); Zhang, H. (Haibo); Prosper-Cardoso, F. (Felipe); Kwon, H. (Hyesoo); Monteil, V. (Vanessa); Slutsky, A.S. (Arthur S.); Mirazimi, A. (Ali); Prado, P. (Patricia)
    We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000– 5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.