Genetics of Preterm Birth

Lengyel, Candice; Muglia, Louis J.; Pavličev, Mihaela

doi:10.1002/9780470015902.a0025448

Cited by 5 publications

(3 citation statements)

References 57 publications

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“…Evidence from family, twin, and case-control studies suggests that genetics plays a role in determining birth timing and a recent GWAS identified a handful of genes linked to prematurity [ 30 ]. Nevertheless, the pathogenesis of PTB and its many subtypes remains poorly understood [ 31 – 33 ].…”

Section: Designmentioning

confidence: 99%

integRATE: a desirability-based data integration framework for the prioritization of candidate genes across heterogeneous omics and its application to preterm birth

et al. 2018

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BackgroundThe integration of high-quality, genome-wide analyses offers a robust approach to elucidating genetic factors involved in complex human diseases. Even though several methods exist to integrate heterogeneous omics data, most biologists still manually select candidate genes by examining the intersection of lists of candidates stemming from analyses of different types of omics data that have been generated by imposing hard (strict) thresholds on quantitative variables, such as P-values and fold changes, increasing the chance of missing potentially important candidates.MethodsTo better facilitate the unbiased integration of heterogeneous omics data collected from diverse platforms and samples, we propose a desirability function framework for identifying candidate genes with strong evidence across data types as targets for follow-up functional analysis. Our approach is targeted towards disease systems with sparse, heterogeneous omics data, so we tested it on one such pathology: spontaneous preterm birth (sPTB).ResultsWe developed the software integRATE, which uses desirability functions to rank genes both within and across studies, identifying well-supported candidate genes according to the cumulative weight of biological evidence rather than based on imposition of hard thresholds of key variables. Integrating 10 sPTB omics studies identified both genes in pathways previously suspected to be involved in sPTB as well as novel genes never before linked to this syndrome. integRATE is available as an R package on GitHub (https://github.com/haleyeidem/integRATE).ConclusionsDesirability-based data integration is a solution most applicable in biological research areas where omics data is especially heterogeneous and sparse, allowing for the prioritization of candidate genes that can be used to inform more targeted downstream functional analyses.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0426-y) contains supplementary material, which is available to authorized users.

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Section: Designmentioning

confidence: 99%

integRATE: a desirability-based data integration framework for the prioritization of candidate genes across heterogeneous omics and its application to preterm birth

et al. 2018

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“…This is so in part to our lack of understanding of whether the syndrome of PTB is human-specific, or whether other organisms experience PTB as well. Although to our knowledge this question has not been heretofore explicitly addressed, experts have so far argued for the uniqueness of human parturition [ 10 , 11 ]. If, as Smith has stated, ‘human parturition is a distinctly human event’ [ 10 ] then it follows that pathologies of parturition, such as PTB, might also be confined to our species.…”

Section: Introductionmentioning

confidence: 99%

Is preterm birth a human-specific syndrome?

Phillips

Abbot

Rokas

2015

EMPH

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Human preterm birth (PTB), a multifactorial syndrome affecting offspring born before 37 completed weeks of gestation, is the leading cause of newborn death worldwide. Remarkably, the degree to which early parturition contributes to mortality in other placental mammals remains unclear. To gain insights on whether PTB is a human-specific syndrome, we examined within- and between-species variation in gestation length across placental mammals and the impact of early parturition on offspring fitness. Within species, gestation length is normally distributed, and all species appear to occasionally give birth before the ‘optimal’ time. Furthermore, human gestation length, like that of many mammalian species, scales proportionally to body mass, suggesting that this trait, like many others, is constrained by body size. Premature humans suffer from numerous cognitive impairments, but little is known of cognitive impairments in other placental mammals. Human gestation differs in the timing of the ‘brain growth spurt’, where unlike many mammals, including closely related primates, the trajectory of human brain growth directly overlaps with the parturition time window. Thus, although all mammals experience early parturition, the fitness costs imposed by the cognitive impairments may be unique to our species. Describing PTB broadly in mammals opens avenues for comparative studies on the physiological and genetic regulators of birth timing as well as the development of new mammalian models of the disease.

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“…Evidence from family, twin, and case-control studies suggests that genetics plays a role in determining birth timing and a recent GWAS identified a handful of genes linked to prematurity [29]. Nevertheless, the pathogenesis of PTB and its many subtypes remains poorly understood [30][31][32].…”

mentioning

confidence: 99%

integRATE: a desirability-based data integration framework for the prioritization of candidate genes across heterogeneous omics and its application to preterm birth

Eidem

Steenwyk

Wisecaver

et al. 2018

Preprint

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Background:The integration of high-quality, genome-wide analyses offers a robust approach to elucidating genetic factors involved in complex human diseases. Even though several methods exist to integrate heterogeneous omics data, most biologists still manually select candidate genes by examining the intersection of lists of candidates stemming from analyses of different types of omics data that have been generated by imposing hard (strict) thresholds on quantitative variables, such as P-values and fold changes, increasing the chance of missing potentially important candidates. Methods:To better facilitate the unbiased integration of heterogeneous omics data collected from diverse platforms and samples, we propose a desirability function framework for identifying candidate genes with strong evidence across data types as targets for follow-up functional analysis. Our approach is targeted towards disease systems with sparse, heterogeneous omics data, so we tested it on one such pathology: spontaneous preterm birth (sPTB). Results:We developed the software integRATE, which uses desirability functions to rank genes both within and across studies, identifying well-supported candidate genes according to the cumulative weight of biological evidence rather than based on imposition of hard thresholds of key variables. Integrating 10 sPTB omics studies identified both genes in pathways previously suspected to be involved in sPTB as well as novel genes never before linked to this syndrome.integRATE is available as an R package on GitHub (https://github.com/haleyeidem/integRATE).3 Conclusions: Desirability-based data integration is a solution most applicable in biological research areas where omics data is especially heterogeneous and sparse, allowing for the prioritization of candidate genes that can be used to inform more targeted downstream functional analyses.

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Genetics of Preterm Birth

Cited by 5 publications

References 57 publications

integRATE: a desirability-based data integration framework for the prioritization of candidate genes across heterogeneous omics and its application to preterm birth

integRATE: a desirability-based data integration framework for the prioritization of candidate genes across heterogeneous omics and its application to preterm birth

Is preterm birth a human-specific syndrome?

integRATE: a desirability-based data integration framework for the prioritization of candidate genes across heterogeneous omics and its application to preterm birth

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