Expanding the stdpopsim species catalog, and lessons learned for realistic genome simulations

Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic datasets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than threefold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed the best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone

Evaluating macroscopic sex estimation methods using genetically sexed archaeological material: The medieval skeletal collection from St John's Divinity School, Cambridge.

OBJECTIVES: In tests on known individuals macroscopic sex estimation has between 70% and 98% accuracy. However, materials used to create and test these methods are overwhelming modern. As sexual dimorphism is dependent on multiple factors, it is unclear whether macroscopic methods have similar success on earlier materials, which differ in lifestyle and nutrition. This research aims to assess the accuracy of commonly used traits by comparing macroscopic sex estimates to genetic sex in medieval English material. MATERIALS AND METHODS: Sixty-six individuals from the 13th to 16th century Hospital of St John the Evangelist, Cambridge, were assessed. Genetic sex was determined using a shotgun approach. Eighteen skeletal traits were examined, and macroscopic sex estimates were derived from the os coxae, skull, and os coxae and skull combined. Each trait was tested for accuracy to explore sex estimates errors. RESULTS: The combined estimate (97.7%) outperformed the os coxae only estimate (95.7%), which outperformed the skull only estimate (90.4%). Accuracy rates for individual traits varied: Phenice traits were most accurate, whereas supraorbital margins, frontal bossing, and gonial flaring were least accurate. The preauricular sulcus and arc compose showed a bias in accuracy between sexes. DISCUSSION: Macroscopic sex estimates are accurate when applied to medieval material from Cambridge. However, low trait accuracy rates may relate to differences in dimorphism between the method derivative sample and the St John's collection. Given the sex bias, the preauricular sulcus, frontal bossing, and arc compose should be reconsidered as appropriate traits for sex estimation for this group.St John's College, Cambridg

Evaluating macroscopic sex estimation methods using genetically sexed archaeological material: The medieval skeletal collection from St John's Divinity School, Cambridge

OBJECTIVES: In tests on known individuals macroscopic sex estimation has between 70% and 98% accuracy. However, materials used to create and test these methods are overwhelming modern. As sexual dimorphism is dependent on multiple factors, it is unclear whether macroscopic methods have similar success on earlier materials, which differ in lifestyle and nutrition. This research aims to assess the accuracy of commonly used traits by comparing macroscopic sex estimates to genetic sex in medieval English material. MATERIALS AND METHODS: Sixty-six individuals from the 13th to 16th century Hospital of St John the Evangelist, Cambridge, were assessed. Genetic sex was determined using a shotgun approach. Eighteen skeletal traits were examined, and macroscopic sex estimates were derived from the os coxae, skull, and os coxae and skull combined. Each trait was tested for accuracy to explore sex estimates errors. RESULTS: The combined estimate (97.7%) outperformed the os coxae only estimate (95.7%), which outperformed the skull only estimate (90.4%). Accuracy rates for individual traits varied: Phenice traits were most accurate, whereas supraorbital margins, frontal bossing, and gonial flaring were least accurate. The preauricular sulcus and arc compose showed a bias in accuracy between sexes. DISCUSSION: Macroscopic sex estimates are accurate when applied to medieval material from Cambridge. However, low trait accuracy rates may relate to differences in dimorphism between the method derivative sample and the St John's collection. Given the sex bias, the preauricular sulcus, frontal bossing, and arc compose should be reconsidered as appropriate traits for sex estimation for this group.status: publishe

Test of the lateral angle method of sex estimation on Anglo-Saxon and Medieval archaeological populations with genetically estimated sex

The lateral angle method of sex estimation is tested on an archaeological population with genetic sex. Casts of the internal auditory canal were made using a quick drying impression material on 90 individuals (76 adults and 14 nonadults) from Anglo-Saxon and Medieval Cambridgeshire. The anterior and posterior angles of the internal auditory canal were measured and the relationship of the angle to genetic sex was tested. The posterior angle failed intraobserver error tests, and only the anterior angle could be analysed. Using the previously published section point for unburnt remains (45°), the method did not adequately distinguish between the sexes. Furthermore, the difference between males and females was insufficient to create population-specific discriminant functions. The anterior angle does not meet the requirements for an osteological method of sex estimation, exhibiting no statistical correlation with genetic sex in this population.This research was supported by the Wellcome Trust “After the Plague: Health and History in Medieval Cambridge” Project (Award No. 2000368/Z/15/Z) and the European Union through the European Research Council Advanced Grant “Making Ancestors: the Politics of Death in European Prehistory” (Award No. 885137)

Test of the lateral angle method of sex estimation on Anglo‐Saxon and medieval archaeological populations with genetically estimated sex

Publication status: PublishedThe lateral angle method of sex estimation is tested on an archaeological population with genetic sex estimates. Casts of the internal auditory canal were made using a quick drying impression material on 90 individuals (76 adults and 14 nonadults) from Anglo‐Saxon and Medieval Cambridgeshire. The anterior and posterior angles of the internal auditory canal were measured, and the relationship of the angle to genetic sex was tested. The posterior angle failed intra‐observer error tests, and only the anterior angle could be analysed. Using the previously published sectioning point for unburnt remains (45°), the method did not adequately distinguish between the sexes. Furthermore, the difference between male and female was insufficient to create population‐specific discriminant functions. The anterior angle does not meet the requirements for an osteological method of sex estimation, exhibiting no statistical correlation with genetic sex in this population

East Anglian Early Neolithic monument burial linked to contemporary Megaliths

In the fourth millennium BCE a cultural phenomenon of monumental burial structures spread along the Atlantic façade. Megalithic burials have been targeted for aDNA analyses, but a gap remains in East Anglia where Neolithic structures were generally earthen or timber. An early Neolithic (3762 – 3648 cal. BCE) burial monument at the site of Trumpington Meadows, Cambridgeshire, U.K. contained the partially articulated remains of at least three individuals. To determine whether this monument fits a pattern present in megalithic burials regarding sex bias, kinship, diet, and relationship to modern populations, teeth and ribs were analysed for DNA and carbon and nitrogen isotopic values respectively. Whole ancient genomes were sequenced from two individuals to a mean genomic coverage of 1.6 and 1.2X and genotypes imputed. Results show that they were brothers from a small population genetically and isotopically similar to previously published British Neolithic individuals, with a level of genome-wide homozygosity consistent with a small island population sourced from continental Europe, but bearing no signs of recent inbreeding. The first Neolithic whole genomes from a monumental burial in East Anglia confirm that this region was connected with the larger pattern of Neolithic megaliths in the British Isles and the Atlantic façade.This work is supported by the Wellcome Trust (Award no. 2000368/Z/15/Z) and St John's College, Cambridge (J.E.R., T.K., R.H., S.A.I, A.R., T.C.O’C., C.C.); the European Union through the European Regional Development Fund (Project No. 2014-2020.4.01.16-0030) (C.L.S.); and the Estonian Research Council personal research grant (PRG243) (C.L.S). E.D’A was supported by Sapienza University of Rome fellowship “borsa di studio per attività di perfezionamento all’estero 2017”

East Anglian early Neolithic monument burial linked to contemporary Megaliths

In the fourth millennium BCE a cultural phenomenon of monumental burial structures spread along the Atlantic façade. Megalithic burials have been targeted for aDNA analyses, but a gap remains in East Anglia, where Neolithic structures were generally earthen or timber. An early Neolithic (3762-3648 cal. BCE) burial monument at the site of Trumpington Meadows, Cambridgeshire, UK, contained the partially articulated remains of at least three individuals. To determine whether this monument fits a pattern present in megalithic burials regarding sex bias, kinship, diet and relationship to modern populations, teeth and ribs were analysed for DNA and carbon and nitrogen isotopic values, respectively. Whole ancient genomes were sequenced from two individuals to a mean genomic coverage of 1.6 and 1.2X and genotypes imputed. Results show that they were brothers from a small population genetically and isotopically similar to previously published British Neolithic individuals, with a level of genome-wide homozygosity consistent with a small island population sourced from continental Europe, but bearing no signs of recent inbreeding. The first Neolithic whole genomes from a monumental burial in East Anglia confirm that this region was connected with the larger pattern of Neolithic megaliths in the British Isles and the Atlantic façade.status: publishe

Test of the lateral angle method of sex estimation on Anglo‐Saxon and Medieval archaeological populations with genetically estimated sex

The lateral angle method of sex estimation is tested on an archaeological population with genetic sex estimates. Casts of the internal auditory canal were made using a quick drying impression material on 90 individuals (76 adults and 14 nonadults) from Anglo-Saxon and Medieval Cambridgeshire. The anterior and posterior angles of the internal auditory canal were measured, and the relationship of the angle to genetic sex was tested. The posterior angle failed intra-observer error tests, and only the anterior angle could be analysed. Using the previously published sectioning point for unburnt remains (45°), the method did not adequately distinguish between the sexes. Furthermore, the difference between male and female was insufficient to create population-specific discriminant functions. The anterior angle does not meet the requirements for an osteological method of sex estimation, exhibiting no statistical correlation with genetic sex in this population.</p

Expanding the stdpopsim species catalog, and lessons learned for realistic genome simulations

Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic data sets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and to the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al.,2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than three-fold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone

Expanding the stdpopsim species catalog, and lessons learned for realistic genome simulations.

Peer reviewed: TrueAcknowledgements: We wish to thank the dozens of workshop attendees, and especially the two dozen or so hackathon participants, whose combined feedback motivated many of the updates made to stdpopsim in the past two years.Funder: Robertson Foundation; FundRef: http://dx.doi.org/10.13039/100013961Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic datasets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than threefold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed the best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone