Monthly Digest :: Blog Posts

Genomic Analysis – Cholera
Through our Center for Vaccine Ethics and Policy, we closely track infectious diseases and vaccines/immunization response in our weekly digest. The current upsurge in cholera in a number of sites – often linked to conflict/post-conflict settings – is troubling as is the contuing severe shortage of OCV [oral cholera vaccine] severely limiting outbreak response. We highlight this article as a powerful application of genomic analysis on the “front-end: projecting and analyzing cholera spread.

medRxiv
2024.11.15.24317392; doi: https://doi.org/10.1101/2024.11.15.24317392
Analysis
Multicountry genomic analysis underscores regional cholera spread in Africa [Pre-Print]
Gerald Mboowa, Nathaniel Lucero Matteson, Collins Kipngetich Tanui, Mpanga Kasonde, Guyguy Kusanzangana Kamwiziku, Olusola Anuoluwapo Akanbi, Jucunu Johane Elias Chitio, Mathews Kagoli, Rene Ghislain Essomba, Alisen Ayitewala, Isaac Ssewanyana, Valentina Josiane Ngo Bitoungui, Adrienne Aziza Amuri, Andrew S Azman, Olajumoke Atinuke Babatunde, Blaise Mboringong Akenji, Anais Broban, Espoir Bwenge Malembaka, Francis Ongole, Chimaobi Emmanuel Chukwu, Nalia Ismael, Otridah Kapona, Osvaldo Laurindo, Placide Kingebeni Mbala, Georges Alain Etoundi Mballa, Imelda Carlos Zulfa Miambo, Alex Ansaye Mwanyongo, Grace Najjuka, Joseph Mutale, Kunda Musonda, Allan Muruta Niyonzima, Mirriam Ethel Nyenje, Michael Popoola, Doreen Mainza Shempela, Christiane Medi Sike, Sofiao Manjor Sitoe, Dorcas Waruguru Wanjohi, Placide Okitayemba Welo, Mtisunge Yelewa, Sebastian Yennan, Lucius Ziba, CholGEN Consortium, Joseph Ephram Bitilinyu-Bangoh, Roma Chilengi, Hamsatou Hadja, Jide Idris, Jose Paulo Mauricio Langa, Daniel Mukadi-Bamuleka, Susan Nabadda, Amanda K Debes, David A Sack, Jean Kaseya, Yenew Kebede Tebeje, Shirlee Wohl, Sofonias Kifle Tessema
Abstract
Cholera remains a significant public health burden in many countries in sub-Saharan Africa, though the exact mechanisms of bacterial emergence and spread remain largely undefined. We generated genomic data from 728 Vibrio cholerae O1 isolates predominantly collected between 2019-2024 to create the largest dataset of V. cholerae genomes sequenced locally in Africa. This dataset enabled us to interrogate recent patterns of spread, including the rapid circulation of the AFR15 lineage associated with unusually large outbreaks in Southern Africa.
We provide evidence for the movement of the AFR15 lineage into new African Member States and confirm previously observed differences in V. cholerae transmission dynamics in West versus East Africa, though cross-border transmission is prevalent on both sides of the continent. Despite observed differences, evolutionary processes are similar across lineages and we find no evidence for significant changes in antimicrobial resistance genotypes.
Overall, our findings emphasize the importance of regionally coordinated cross-border surveillance and interventions, while also demonstrating the critical role of locally generated genomic data in understanding the spread of cholera in Africa.

Molecular Informatics
Unprecedented advances in omics and informatics are helping drive a revolution in disease prevention, detection, and management. The editorial below provides a useful overview on a set of key articles in Frontiers in Medicine around molecular informatics in precision medicine.

Frontiers in Medicine
https://www.frontiersin.org/journals/medicine/volumes?volume-id=1237
Editorial
Molecular Informatics in Precision Medicine
Abdul Azeez Sayed, Hari S Sharma, PhD, DSc, FIABS, J. Francis Borgio
Accepted on 22 Nov 2024
Introduction
The emerging concept in medicine shifts towards precision medicine personalised to an individual’s unique genetic makeup and environmental factors. By integrating advanced molecular technologies such as genomics, transcriptomics, proteomics, metabolomics and microbiomics we can unlock the potential to revolutionize healthcare.

Molecular informatics plays a crucial role in this transformation. By analysing vast amounts of biological data, researchers can identify genetic markers, predict disease risk and develop personalized treatment strategies. This research topic deals the latest advancements in molecular informatics, exploring how these technologies can be connected to improve patient outcomes.

Key areas of focus include:
(i) next-generation sequencing, a leveraging cutting-edge sequencing technologies to unravel complex genetic variations,
(ii) computer-aided drug discovery for utilizing computational tools to accelerate drug discovery and development,
(iii) molecular modeling and simulation for simulating biological processes at the molecular level to gain insights into disease mechanisms and
(iv) bioinformatics specially applying computational methods to analyze and interpret biological data.

Through a comprehensive exploration of these topics, this collection of articles aims to provide a valuable resource for researchers, clinicians and industry professionals working at the forefront of precision medicine. By understanding the power of molecular informatics, we can move closer to a future where healthcare is truly personalized.

Africa CDC launches initiatives to advance molecular diagnostics and genomic surveillance in Africa
Addis Ababa, Ethiopia – 24 April 2024 – The Africa Centres for Disease Control and Prevention (Africa CDC) kicked-off two groundbreaking projects: the Integrated Genomic Surveillance and Data Sharing Platform (IGS) and Integrated Genomic Surveillance for Outbreak Detection (DETECT). These initiatives, co-funded by the European Union, are poised to fortify the Africa Pathogen Genomics Initiative (Africa PGI 2.0), enhancing the capacity of member states for molecular detection of outbreaks, AMR genomic surveillance, and timely data sharing across Africa…

Through these projects implemented by the European Health and Digital Executive Agency (HaDEA), Africa CDC, and HERA, in partnership with African Union (AU) Member States, the African Society for Laboratory Medicine (ASLM) and the Africa Public Health Foundation (APHF), will strengthen national and regional capacities to promptly detect outbreaks, support the integration of AMR genomic surveillance, and facilitate swift and high-quality data sharing for public health decision-making…

Africa CDC’s shift towards Africa PGI 2.0 signifies a transition from emergency response to building an optimized, resilient, and integrated molecular diagnostic and genomic surveillance ecosystem. It is critical and timely to incorporate lessons from the COVID-19 pandemic, and empower national and regional reference laboratories to expand their capabilities to detect and characterize epidemic and pandemic-prone diseases. As demonstrated in previous outbreaks, molecular detection and genomic sequencing improves early detection and response to public health emergencies.

Mr. Nqobile Ndlovu, CEO of ASLM, remarked, “The launch of the two projects is pivotal in devising scalable and sustainable approaches for integrating molecular diagnostics and sequencing within Africa’s routine surveillance structures. We are eager to collaborate with the Africa CDC and HERA to strengthen laboratory systems ensuring effective responses to current and future health threats”…

HHMI – Howard Hughes Medical Institute
Press Room
Scaling Up Precision Genome Editing
Precision genome editing tools – including prime editing – enable scientists to model genetic variants in their native environment. Now, researchers have developed a framework for engineering and measuring the effects of thousands of genetic mutations simultaneously while accurately quantifying the efficiency of prime editing. They’ve even found that some mutations once considered to be inconsequential or nonpathogenic may contribute to cancers.
March 15, 2024

Public Health Genomics
2024, Vol. 27, No. 1
Perspectives
Next-Generation Public Health Genomics: A Call to Assess the Equitable Implementation, Population Health Impact, and Sustainability of Precision Public Health Applications
Megan C. Roberts; Caitlin G. Allen
The field of Public Health Genomics recently celebrated its twenty-fifth anniversary [1]. Defined by the CDC as responsible and effective translation of genome-based knowledge and technologies for the benefit of population health, public health genomics applications have expanded beyond newborn screening to other applications poised to improve public health [2, 3]. Yet despite the promise and potential for public health genomics, the population health impact and sustainability of public health genomics applications has yet to be fully measured and achieved. Further access to public health genomics applications has been lower among underrepresented racial and ethnic communities, rural communities, and groups with lower education and income [2], deepening concerns that the field could exacerbate rather than redress health inequities [4, 5]. As we enter the next generation of public health genomics, we must shift our focus from not only understanding the collection of genetic risk information and related needs, but also the real-world use of this precision information and its impact on population health outcomes and health equity over time…

Nature Reviews Drug Discovery
Volume 23 Issue 3, March 2024
Comment 06 Feb 2024
The Bespoke Gene Therapy Consortium: facilitating development of AAV gene therapies for rare diseases
A public–private partnership managed by the FNIH aims to address biological, manufacturing and regulatory challenges to the development of gene therapies for rare diseases.
P. J. Brooks, Timothy M. Miller, Joni L. Rutter

Annals of Internal Medicine
February 2024 Volume 177, Issue 2
Original Research
Gene Therapy Versus Common Care for Eligible Individuals With Sickle Cell Disease in the United States – A Cost-Effectiveness Analysis
Anirban Basu, PhD, … et al.
Pages:155–164
The U.S. Food and Drug Administration recently approved 2 genetic therapies for sickle cell disease. Both therapies increase the production of nonsickling red blood cells, either fetal hemoglobin or a gene therapy–derived hemoglobin similar to hemoglobin A. In addition, both therapies require collection of a patient’s stem cells, modification of the cells in the laboratory, high-dose chemotherapy to remove existing bone marrow cells, and a single-dose infusion of the patient’s modified stem cells. This article uses 2 different cost-effectiveness models to estimate whether these therapies provide enough value to justify their high costs.

Cell
Feb 29, 2024 Volume 187 Issue 5 p1017-1314
Leading Edge
Five decades of genetics and genomics
The Cell Editorial Team
Some of the most significant discoveries in the life sciences over the last 50 years stem from genetics and genomics. This field has also seen large-scale collaborative efforts yield fundamental milestones and results, such as the Human Genome Project. Despite a long road ahead, progress in both basic and clinical genetics now drives sweeping efforts to cure complex human ailments such as blood and psychiatric disorders, metabolic diseases, cancer, and neurodegeneration. While these large tent-pole endeavors receive the most attention, cutting-edge modern genetics techniques are foundational to the science that happens daily across the biomedical life sciences.

Past, present, and future of CRISPR genome editing technologies
Martin Pacesa, Oana Pelea, Martin Jinek
A broad survey of the genome editing landscape, highlighting the potential and the challenges of genome editing applications for research and therapeutics.

Genomic Medicine :: Governance, Ethics, Policy, Practice: A Monthly Digest

---

October 2023 :: Number 08

Genomic medicine – spanning preclinical basic science through clinical development and translation into daily patient interventions – continues to evolve at an extraordinary pace. Advances in the scientific and technical dimensions of genomic medicine are extensively communicated through the peer-reviewed journal ecology and supporting grey literature.

Complementing this technical literature is a growing body of commentary, analysis and research around the governance, ethics, regulation, and policy dimensions of genomic medicine. Much of this content is communicated through academic journals and grey literature, but is also appearing in the general media. This digest intends to capture and curate the most substantive examples of this non-technical content.

In aggregating and editing this digest, we directly review a broad spectrum of peer-reviewed journals and grey literature, as well as announcements and strategic actions from various practice domains and organization types including international agencies, INGOs, governments/regulatory bodies, academic and research institutions, consortia and collaborations, foundations, and commercial organizations. More broadly, we utilize Google Scholar’s alert capability to scan current literature. We acknowledge that this approach and scope yields an indicative and not an exhaustive digest p

Genomic medicine – spanning pre-clinical basic science through clinical development and translation to daily patient interventions – continues to evolve at an extraordinary pace. Advances in the scientific and technical dimensions of genomic medicine are extensively communicated through the peer-reviewed journal literature and supporting grey literature.

Complementing this technical literature is a growing body of research, analysis and commentary addressing the governance, ethics, regulation, and policy dimensions of genomic medicine. Much of this content is communicated through academic journals and grey literature. This digest intends to capture and curate the most substantive examples of this non-technical content.

Further, we intend this digest to provide a useful summary of key strategic and programmatic announcements from across the genomic medicine ecology as issued by multilateral agencies, INGOs, governments/regulatory bodies, academic and research institutions, consortiums and collaborations, foundations, investors, and commercial organizations.

Given the complexity and velocity of the field, we recognize that this digest will be indicative, not exhaustive. We invite suggestions and ideas on how it can evolve to be more useful.

The digest is a program of the GE2P2 Global Foundation which is solely responsible for its content. Questions and comments should be directed to the Editor david.r.curry@ge2p2global.org or Associate Editor daima.bukini@ge2p2global.org.