Biology subjects

Siwo, G. H.

Publications and source records attributed to Siwo, G. H..

3 recordsLinked to original sources

bioRxiv2018

“Global Transcriptional Response to CRISPR/CAS9-AAV6 Based Genome Editing” Matches Transcriptional Response to Specific Small Molecule Perturbations

Cromer et al. [1] recently reported global transcriptional changes occuring in cells in response to CRISPR/Cas9 gene editing. Using a CD34+ hematopoietic and progenitor stem cell model, they observed differentially expressed genes enriched for immune, stress and apoptotic processes following treatment with a CRISPR/Cas9-AAV6 genome-editing system. Following treatment with Cas9s mRNA they observed transcriptional changes enriched for viral response as well as a downregulation of metabolic and cell cycle processes. Similarly, they observed a downregulation of metabolic processes in response to electroporation. Surprisingly, no enrichment for viral response genes was observed following treatment with AAV6 while minor transcriptional changes enriched for DNA damage signature occurred in response to Cas9/sgRNA ribonucleoprotein.

molecular biology↗

bioRxiv2018

The Global State of Genome Editing

Genome editing technologies hold great promise in fundamental biomedical research, development of treatments for animal and plant diseases, and engineering biological organisms for food and industrial applications. Therefore, a global understanding of the growth of the field is needed to identify challenges, opportunities and biases that could shape the impact of the technology. To address this, this work applies automated literature mining of scientific publications on genome editing in the past year to infer research trends in 2 key genome editing technologies-CRISPR/Cas systems and TALENs. The study finds that genome editing research is disproportionately distributed between and within countries, with researchers in the US and China accounting for 50% of authors in the field whereas countries across Africa are underrepresented. Furthermore, genome editing research is also disproportionately being explored on diseases such as cancer, Duchene Muscular Dystrophy, sickle cell disease and malaria. Gender biases are also evident in genome editing research with considerably fewer women as principal investigators. The results of this study suggest that automated mining of scientific literature could help identify biases in genome editing research as a means to mitigate future inequalities and tap the full potential of the technology.

genomics↗

bioRxiv2017

Prediction of Molecular Mechanisms of Breast Cancer Metastasis

Metastasis -the spread of cancer to other parts of the body- causes 90% of cancer deaths, underlies major health complications in cancer patients and renders most cancers incurable. Unfortunately, the molecular mechanisms underlying the process are poorly understood and therapeutics to block it remain elusive. Here, we present a computational technique for scanning genome-scale regulatory networks for potential genes associated with metastasis. First, we demonstrate that in the breast cancer cell line MCF7, the commonly dysregulated cancer biomarkers TP53, ERBB2, ESR1 and PGR are closely connected to known metastasis genes with a significant proportion being 2nd degree neighbors of a given biomarker. Next, we identify genes whose 2nd degree neighbors are connected in a similar manner to these biomarkers. Consequently, these are referred to as metastasis associated genes or MAGs. We identify 190 genes that are TP53-MAGs, 22 ERBB2-MAGs, 240 ESR1-MAGs and 84 PGR-MAGs (FDR adjusted P <0.001). Analysis of the MAGs reveals statistically significant enrichment with biological functions previously associated with metastasis including the extracellular matrix (ECM) receptor interaction, focal adhesion, cytokine-cytokine receptor interaction and chemokine signaling. The biological significance of MAGs is further supported by their enrichment with experimentally validated binding sites for transcription factors that regulate metastasis, for example BACH1- a master regulator of breast cancer metastasis to bone. The predicted MAGs are also clinically relevant as therapeutic targets for metastasis blocking agents. Specifically, genes that are perturbed by drugs and miRNAs that influence metastasis are enriched with MAGs. Furthermore, some MAGs are associated with patient survival and provide insights into the proclivity for breast cancer subtypes to preferentially spread to specific organs. The results of this study imply that aberrations in primary tumors may constrict metastasis trajectories. This could enable the prediction of organ specific metastases based on aberrations in the primary tumor and lay a foundation for future studies on individualized or personalized models of metastasis. The approach is potentially scalable across other cancers and has clinical implications.

cancer biology↗