scholarly journals Network analysis reveals rare disease signatures across multiple levels of biological organization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pisanu Buphamalai ◽  
Tomislav Kokotovic ◽  
Vanja Nagy ◽  
Jörg Menche
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Single Gene ◽  
Genetic Diseases ◽  
Physical Interaction ◽  
Biological Organization ◽  
Network Layers ◽  
Disease Module ◽  
Gene Defects ◽  
The Impact

AbstractRare genetic diseases are typically caused by a single gene defect. Despite this clear causal relationship between genotype and phenotype, identifying the pathobiological mechanisms at various levels of biological organization remains a practical and conceptual challenge. Here, we introduce a network approach for evaluating the impact of rare gene defects across biological scales. We construct a multiplex network consisting of over 20 million gene relationships that are organized into 46 network layers spanning six major biological scales between genotype and phenotype. A comprehensive analysis of 3,771 rare diseases reveals distinct phenotypic modules within individual layers. These modules can be exploited to mechanistically dissect the impact of gene defects and accurately predict rare disease gene candidates. Our results show that the disease module formalism can be applied to rare diseases and generalized beyond physical interaction networks. These findings open up new venues to apply network-based tools for cross-scale data integration.

Cooccurrence of Two Different Genetic Diseases: A Case of Valproic Acid Hepatotoxicity in Nicolaides–Baraitser Syndrome (SMARCA2 Mutation)—Due to a POLG1-Related Effect?

2019 ◽  
Vol 51 (01) ◽  
pp. 049-052
Author(s):  
Benedikt Hofmeister ◽  
Celina von Stülpnagel ◽  
Steffen Berweck ◽  
Angela Abicht ◽  
Gerhard Kluger ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Literature Review ◽  
Rare Disease ◽  
Clinical Features ◽  
Rare Diseases ◽  
Rare Complication ◽  
Genetic Diseases ◽  
Related Effect ◽  
Higher Sensitivity ◽  
Polg1 Mutation

AbstractNicolaides–Baraitser syndrome (NCBRS) is a rare disease caused by a mutation in the SMARCA2 gene. Clinical features include craniofacial dysmorphia and abnormalities of the limbs, as well as intellectual disorder and often epilepsy. Hepatotoxicity is a rare complication of the therapy with valproic acid (VPA) and a mutation of the polymerase γ (POLG) might lead to a higher sensitivity for liver hepatotoxicity. We present a patient with the coincidence of two rare diseases, the NCBRS and additionally a POLG1 mutation in combination with a liver hepatotoxicity. The co-occurrence in children for two different genetic diseases is discussed with the help of literature review.

scholarly journals Research and Management of Rare Diseases in the COVID-19 Pandemic Era: Challenges and Countermeasures

2021 ◽  
Vol 9 ◽  
Author(s):  
Sanjana Fatema Chowdhury ◽  
Syed Muktadir Al Sium ◽  
Saeed Anwar
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Management Strategies ◽  
Routine Care ◽  
Ongoing Research ◽  
The People ◽  
Number Of Patients ◽  
High Level ◽  
Disease Community

The ongoing coronavirus disease 2019 (COVID-19) pandemic has disrupted every aspect of our life. The need to provide high-level care for an enormous number of patients with COVID-19 infection during this pandemic has impacted resourcing for and restricted the routine care of all non-COVID-19 conditions. Since the beginning of the pandemic, the people living with rare disorders, who represent a marginalized group of the population even in a normal world, have not received enough attention that they deserve. Due to the pandemic situation, they have experienced (and experiencing) an extreme inadequacy of regular clinical services, counseling, and therapies they need, which have made their life more vulnerable and feel more marginalized. Besides, the clinicians, researchers, and scientists working on rare genetic diseases face extra challenges due to the pandemic. Many ongoing research projects and clinical trials for rare and genetic diseases were stalled to avoid patients' and research staff's transmission to COVID-19. Still, with all the odds, telehealth and virtual consultations for rare disease patients have shown hope. The clinical, organizational, and economic challenges faced by institutions, patients, their families, and the caregivers during the pandemic indicate the importance of ensuring continuity of care in managing rare diseases, including adequate diagnostics and priority management strategies for emergencies. In this review, we endeavored to shed light on the issues the rare disease community faces during the pandemic and the adaptations that could help the rare disease community to better sustain in the coming days.

Impact of genomics on biopharmaceutical industry: rare diseases as disruptive innovation

2019 ◽  
Vol 11 (2) ◽  
pp. 241-260 ◽  
Author(s):  
Mark J. Ahn ◽  
Amir Shaygan ◽  
Charles Weber
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Dynamic Capabilities ◽  
Disruptive Innovation ◽  
Increasing Returns ◽  
Biopharmaceutical Industry ◽  
Content Type ◽  
Enterprise Value ◽  
The Impact ◽  
Value Growth

Purpose Using a dynamic capabilities lens, this paper aims to study the impact of genomics generally and gene therapy specifically on the rare disease sector of the biopharmaceutical industry. Design/methodology/approach In this study, 24 genomics-based, rare disease-focused biopharma companies were studied and several variables were tested with respect to enterprise value growth. The companies were analyzed as a group of rare disease firms, as well as by size. Findings The authors found that number of employees, revenues, number of pipeline and marketed products and retained earnings are strongly correlated (in that order) with enterprise value in rare disease focused biopharma companies. These correlations seem to be weaker as a company’s market capitalization size decreases, indicating that there tends to be increasing returns to scale. Research limitations/implications This study found that increasing rates of cumulative returns to enterprise value growth depends on accumulating knowledge-based employees and expanding product portfolios of disruptive genomics-based technologies for treating rare diseases. Aggregating skilled and innovative employees (especially in bigger companies) can be seen as a cumulative bolstering factor in leveraging dynamic capabilities which can be recognized, understood and transformed into commercial success (i.e. increasing returns in enterprise value). In other words, technology managers’ job is to manage not only the financial aspects of the technology but also human resources, asset configuration and strategic alliances efficiently toward faster and better innovation. Strong dynamic capabilities can be formed with the accumulation of experience, articulation and codification of knowledge and an adaptive ability to change the way they solve problems as their environment transforms. Originality/value This is the first study to demonstrate and measure a relationship between dynamic capabilities and enterprise value in genomics-based rare disease firms. Further, this study highlights the importance of building the capability and capacity to absorb expertise and accumulate knowledge for new product innovations and sustainable competitive advantage in industries characterized by disruptive innovation.

scholarly journals PRIORITY NEEDS REFERRED BY FAMILIES OF RARE DISEASE PATIENTS

2016 ◽  
Vol 25 (4) ◽  
Author(s):  
Geisa dos Santos Luz ◽  
Mara Regina Santos da Silva ◽  
Francine DeMontigny
Keyword(s):  
Rare Disease ◽  
Social Services ◽  
Rare Diseases ◽  
Healthcare Services ◽  
Strong Impact ◽  
Structured Interviews ◽  
The Family ◽  
Priority Needs ◽  
The Impact ◽  
The Relationship

ABSTRACT Rare diseases cause strong impact in families and generate needs beyond those associated with the most frequent diseases. Some of these needs are the inclusion of new responsibilities and the relationship with the healthcare and social services. This study is aimed at identifying the priority needs of families of rare disease patients as perceived from the time of diagnosis. This is a qualitative study conducted with 16 relatives of rare disease patients who live in the state of Rio Grande do Sul. Data were collected from November 2012 to March 2013, through semi-structured interviews and submitted to content analysis, based on the bioecological system of human development. The results indicated the following priority needs: access to social and healthcare services; knowledge about rare diseases; social support structures; acceptance and social integration; preservation of personal and family life. It was concluded that (re)organizing services and meeting the specific needs are preconditions to qualify nursing care and soften the impact the rare disease has on the family.

scholarly journals RDmap: A Map for Exploring Rare Diseases

2021 ◽  
Author(s):  
Jian Yang ◽  
Cong Dong ◽  
Huilong Duan ◽  
Qiang Shu ◽  
Haomin Li
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Distance Matrix ◽  
Disease Diagnosis ◽  
Human Phenotype ◽  
Pathogenic Genes ◽  
Disease Information ◽  
Rare Genetic Diseases ◽  
Interactive Map

Abstract Background: The complexity of the phenotypic characteristics and molecular bases of many rare human genetic diseases makes the diagnosis of such diseases a challenge for clinicians. A map for visualizing, locating and navigating rare diseases based on similarity will help clinicians and researchers understand and easily explore these diseases. Methods: A distance matrix of rare diseases included in Orphanet was measured by calculating the quantitative distance among phenotypes and pathogenic genes based on Human Phenotype Ontology (HPO) and Gene Ontology (GO), and each disease was mapped into Euclidean space. A rare disease map, enhanced by clustering classes and disease information, was developed based on ECharts. Results: A rare disease map called RDmap was published at http://rdmap.nbscn.org. Total 3,287 rare diseases are included in the phenotype-based map, and 3,789 rare genetic diseases are included in the gene-based map; 1,718 overlapping diseases are connected between two maps. RDmap works similarly to the widely used Google Map service and supports zooming and panning. The phenotype similarity base disease location function performed better than traditional keyword searches in an in silico evaluation, and 20 published cases of rare diseases also demonstrated that RDmap can assist clinicians in seeking the rare disease diagnosis. Conclusion: RDmap is the first user-interactive map-style rare disease knowledgebase. It will help clinicians and researchers explore the increasingly complicated realm of rare genetic diseases.

scholarly journals Genomics of rare genetic diseases—experiences from India

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Sridhar Sivasubbu ◽  
◽  
Vinod Scaria
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Collaborative Research ◽  
Disease Burden ◽  
Genetic Diseases ◽  
Community Services ◽  
Health Concern ◽  
Healthy Population ◽  
Rare Genetic Diseases ◽  
Research Initiative

Abstract Home to a culturally heterogeneous population, India is also a melting pot of genetic diversity. The population architecture characterized by multiple endogamous groups with specific marriage patterns, including the widely prevalent practice of consanguinity, not only makes the Indian population distinct from rest of the world but also provides a unique advantage and niche to understand genetic diseases. Centuries of genetic isolation of population groups have amplified the founder effects, contributing to high prevalence of recessive alleles, which translates into genetic diseases, including rare genetic diseases in India. Rare genetic diseases are becoming a public health concern in India because a large population size of close to a billion people would essentially translate to a huge disease burden for even the rarest of the rare diseases. Genomics-based approaches have been demonstrated to accelerate the diagnosis of rare genetic diseases and reduce the socio-economic burden. The Genomics for Understanding Rare Diseases: India Alliance Network (GUaRDIAN) stands for providing genomic solutions for rare diseases in India. The consortium aims to establish a unique collaborative framework in health care planning, implementation, and delivery in the specific area of rare genetic diseases. It is a nation-wide collaborative research initiative catering to rare diseases across multiple cohorts, with over 240 clinician/scientist collaborators across 70 major medical/research centers. Within the GUaRDIAN framework, clinicians refer rare disease patients, generate whole genome or exome datasets followed by computational analysis of the data for identifying the causal pathogenic variations. The outcomes of GUaRDIAN are being translated as community services through a suitable platform providing low-cost diagnostic assays in India. In addition to GUaRDIAN, several genomic investigations for diseased and healthy population are being undertaken in the country to solve the rare disease dilemma. In summary, rare diseases contribute to a significant disease burden in India. Genomics-based solutions can enable accelerated diagnosis and management of rare diseases. We discuss how a collaborative research initiative such as GUaRDIAN can provide a nation-wide framework to cater to the rare disease community of India.

EXPLORING VALUES OF HEALTH TECHNOLOGY ASSESSMENT AGENCIES USING REFLECTIVE MULTICRITERIA AND RARE DISEASE CASE

2017 ◽  
Vol 33 (4) ◽  
pp. 504-520 ◽  
Author(s):  
Mireille M. Goetghebeur ◽  
Monika Wagner ◽  
Dima Samaha ◽  
William O'Neil ◽  
Danielle Badgley ◽  
...  
Keyword(s):  
Health Technology Assessment ◽  
Rare Disease ◽  
Rare Diseases ◽  
Technology Assessment ◽  
Ethical Reasoning ◽  
Stakeholder Involvement ◽  
Health Technology ◽  
Trade Offs ◽  
Disease Case ◽  
The Impact

Objectives: Tackling ethical dilemmas faced by reimbursement decision makers requires deeper understanding of values on which health technology assessment (HTA) agencies are founded and how trade-offs are made. This was explored in this study including the case of rare disease.Methods: Representatives from eight HTA explored values on which institutions are founded using a narrative approach and reflective multicriteria (developed from EVIDEM, criteria derived from ethical imperatives of health care). Trade-offs between criteria and the impact of incorporating defined priorities (including for rare diseases) were explored through a quantitative values elicitation exercise.Results: Participants reported a diversity of substantive and procedural values with a common emphasis on scientific excellence, stakeholder involvement, independence, and transparency. Examining the ethical imperatives behind EVIDEM criteria was found to be useful to further explore substantive values. Most criteria were deemed to reflect institutions’ values, while 70 percent of the criteria were reported by at least half of participants to be considered formally by their institutions. The quantitative values elicitation highlighted the difficulty to balance imperatives of “alleviating or preventing patient suffering,” “serving the whole population equitably,” “upholding healthcare system sustainability,” and “making decisions informed by evidence and context” but may help share the ethical reasoning behind decisions. Incorporating “Priorities” (including for rare diseases) helped reveal trade-offs from other criteria and their underlying ethical imperatives.Conclusions: Reflective multicriteria are useful to explore substantive values of HTAs, reflect how these values and their ethical underpinnings can be operationalized into criteria, and explore the ethical reasoning at the heart of the healthcare debate.

PP154 Funding Of Treatments For Rare Diseases In Singapore

2020 ◽  
Vol 36 (S1) ◽  
pp. 17-18
Author(s):  
Fiona Pearce ◽  
Liang Lin ◽  
Kwong Ng
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Evaluation Process ◽  
Public Healthcare ◽  
Clinical Group ◽  
Eligibility Criteria ◽  
Number Of Patients ◽  
Emerging Treatments ◽  
Multi Stakeholder

IntroductionA national multi-stakeholder charity fund has been established in Singapore to provide targeted support to patients with rare genetic diseases whose treatment costs remain unaffordable despite government subsidies and insurance. This presentation will provide an overview of the evaluation, price-setting, and stakeholder engagement processes established to inform the first list of drugs eligible for funding under the Rare Disease Fund (RDF).MethodsThe local prevalence of “rare” and “ultra-rare” conditions was defined in line with international rates (≤4 in 10,000 and <2 in 50,000, respectively) to facilitate an analysis of the rare disease landscape in Singapore, and to identify patients most likely to benefit from the RDF. Public healthcare institutions proposed drugs for consideration, which underwent technical evaluation and were then assessed in line with eligibility criteria by an expert clinical group and prioritized by decision makers for funding.ResultsThe number of patients with select rare diseases in Singapore was lower than global estimates contextualized to the local setting. Supporting clinical evidence, funding decisions from overseas health technology assessment agencies, reference pricing considerations, and local budget impact analyses informed the first tranche of drugs (n = 5) recommended. Extensive engagement with pharmaceutical companies was needed to negotiate fair drug prices relative to overseas countries. Additional treatments will be included in the RDF once sufficient funds are raised.ConclusionsAs the evaluation process evolves, wider considerations of disease and treatment experiences from a multi-stakeholder standpoint should be included to inform RDF listings. There is also a need to balance the sustainability of the fund in the longer term with the number of emerging treatments that may require coverage in the future.

scholarly journals RDmap: a map for exploring rare diseases

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jian Yang ◽  
Cong Dong ◽  
Huilong Duan ◽  
Qiang Shu ◽  
Haomin Li
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Distance Matrix ◽  
Disease Diagnosis ◽  
Human Phenotype ◽  
Pathogenic Genes ◽  
Disease Information ◽  
Rare Genetic Diseases ◽  
Interactive Map

Abstract Background The complexity of the phenotypic characteristics and molecular bases of many rare human genetic diseases makes the diagnosis of such diseases a challenge for clinicians. A map for visualizing, locating and navigating rare diseases based on similarity will help clinicians and researchers understand and easily explore these diseases. Methods A distance matrix of rare diseases included in Orphanet was measured by calculating the quantitative distance among phenotypes and pathogenic genes based on Human Phenotype Ontology (HPO) and Gene Ontology (GO), and each disease was mapped into Euclidean space. A rare disease map, enhanced by clustering classes and disease information, was developed based on ECharts. Results A rare disease map called RDmap was published at http://rdmap.nbscn.org. Total 3287 rare diseases are included in the phenotype-based map, and 3789 rare genetic diseases are included in the gene-based map; 1718 overlapping diseases are connected between two maps. RDmap works similarly to the widely used Google Map service and supports zooming and panning. The phenotype similarity base disease location function performed better than traditional keyword searches in an in silico evaluation, and 20 published cases of rare diseases also demonstrated that RDmap can assist clinicians in seeking the rare disease diagnosis. Conclusion RDmap is the first user-interactive map-style rare disease knowledgebase. It will help clinicians and researchers explore the increasingly complicated realm of rare genetic diseases.

scholarly journals Impact of single and combined rare diseases on adult inpatient outcomes: a retrospective, cross-sectional study of a large inpatient population

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Reka Maria Blazsik ◽  
Patrick Emanuel Beeler ◽  
Karol Tarcak ◽  
Marcus Cheetham ◽  
Viktor von Wyl ◽  
...  
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Cross Sectional Study ◽  
Hospital Death ◽  
Sectional Study ◽  
Cross Sectional ◽  
Inpatient Outcomes ◽  
Increased Risk ◽  
Icd 10 ◽  
The Impact

Abstract Background Little is known about the impact of rare diseases on inpatient outcomes. Objective To compare outcomes of inpatients with 0, 1, or > 1 rare disease. A catalogue of 628 ICD-10 coded rare diseases was applied to count rare diseases. Design Retrospective, cross-sectional study. Subjects 165,908 inpatients, Swiss teaching hospital. Main measures Primary outcome: in-hospital mortality. Secondary outcomes: length of stay (LOS), intensive care unit (ICU) admissions, ICU LOS, and 30-day readmissions. Associations with single and combined rare diseases were analyzed by multivariable regression. Key results Patients with 1 rare disease were at increased risk of in-hospital death (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.67, 1.95), combinations of rare diseases showed stronger associations (OR 2.78; 95% CI 2.39, 3.23). Females with 1 rare disease had an OR of 1.69 (95% CI 1.50, 1.91) for in-hospital death, an OR of 2.99 (95% CI 2.36, 3.79) if they had a combination of rare diseases. Males had an OR of 1.85 (95% CI 1.68, 2.04) and 2.61 (95% CI 2.15, 3.16), respectively. Rare diseases were associated with longer LOS (for 1 and > 1 rare diseases: increase by 28 and 49%), ICU admissions (for 1 and > 1: OR 1.64 [95% CI 1.57, 1.71] and 2.23 [95% CI 2.01, 2.48]), longer ICU LOS (for 1 and > 1 rare diseases: increase by 14 and 40%), and 30-day readmissions (for 1 and > 1: OR 1.57 [95% CI 1.47, 1.68] and 1.64 [95% CI 1.37, 1.96]). Conclusions Rare diseases are independently associated with worse inpatient outcomes. This might be the first study suggesting even stronger associations of combined rare diseases with in-hospital deaths, increased LOS, ICU admissions, increased ICU LOS, and 30-day readmissions.

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