Algorithmic approaches to clonal reconstruction in heterogeneous cell populations

Background: The reconstruction of clonal haplotypes and their evolutionary history in evolving populations is a common problem in both microbial evolutionary biology and cancer biology. The clonal theory of evolution provides a theoretical framework for modeling the evolution of clones.Results: In this paper, we review the theoretical framework and assumptions over which the clonal reconstruction problem is formulated. We formally define the problem and then discuss the complexity and solution space of the problem. Various methods have been proposed to find the phylogeny that best explains the observed data. We categorize these methods based on the type of input data that they use (space-resolved or time-resolved), and also based on their computational formulation as either combinatorial or probabilistic. It is crucial to understand the different types of input data because each provides essential but distinct information for drastically reducing the solution space of the clonal reconstruction problem. Complementary information provided by single cell sequencing or from whole genome sequencing of randomly isolated clones can also improve the accuracy of clonal reconstruction. We briefly review the existing algorithms and their relationships. Finally we summarize the tools that are developed for either directly solving the clonal reconstruction problem or a related computational problem.Conclusions: In this review, we discuss the various formulations of the problem of inferring the clonal evolutionary history from allele frequeny data, review existing algorithms and catergorize them according to their problem formulation and solution approaches. We note that most of the available clonal inference algorithms were developed for elucidating tumor evolution whereas clonal reconstruction for unicellular genomes are less addressed. We conclude the review by discussing more open problems such as the lack of benchmark datasets and comparison of performance between available tools.     

Algorithmic approaches to selecting control clones in DNA array hybridization experiments

We study the problem of selecting control clones in DNA array hybridization experiments. The problem arises in the OFRG method for analyzing microbial communities. The OFRG method performs classification of rRNA gene clones using binary fingerprints created from a series of hybridization experiments, where each experiment consists of hybridizing a collection of arrayed clones with a single oligonucleotide probe. This experiment produces analog signals, one for each clone, which then need to be classified, that is, converted into binary values 1 and 0 that represent hybridization and non-hybridization events. In addition to the sample rRNA gene clones, the array contains a number of control clones needed to calibrate the classification procedure of the hybridization signals. These control clones must be selected with care to optimize the classification process. We formulate this as a combinatorial optimization problem called Balanced Covering. We prove that the problem is NP-hard, and we show some results on hardness of approximation. We propose approximation algorithms based on randomized rounding, and we show that, with high probability, our algorithms approximate well the optimum solution. The experimental results confirm that the algorithms find high quality control clones. The algorithms have been implemented and are publicly available as part of the software package called CloneTools.     

Theoretical models of species' borders: single species approaches

The range of potential mechanisms limiting species' distributions in space is nearly as varied and complex as the diversity of life itself. Yet viewed abstractly, a species' border is a geographic manifestation of a species' demographic responses to a spatially and temporally varying world. Population dynamic models provide insight into the different routes by which range limits can arise owing to gradients in demographic rates. In a metapopulation context, for example, range limits may be caused by gradients in extinction rates, colonization rates or habitat availability. We have consider invasion models in uniform and heterogeneous environments as a framework for understanding non-equilibrium range limits, and explore conditions under which invasions may cease to spread leaving behind a stationary range limit. We conclude that non-equilibrial range dynamics need further theoretical and empirical attention.     

Multidisciplinary approaches for species delimitation in Sisyrinchium (Iridaceae)

A remarkable morphological similarity in natural populations of different groups of Sisyrinchium spp. (Iridaceae) makes classification of some species difficult. The present paper focused on two morphological categories of S. sellowianum (MC‐I and MC‐II) with distinct morphological traits. Morphological, cytogenetic, reproductive biology and genetic studies were performed, aiming to elucidate and better characterize such variation. The basic chromosome number established for the species was x = 9 and diploid and tetraploid populations were observed for MC‐I, whereas MC‐II showed only diploid populations. Different pollen morphologies were recognized in each morphological category. Based on pollination experiments, MC‐I is out‐crossing, whereas MC‐II is selfing. The populations were highly differentiated (F_ST = 0.46, θ^B = 0.62). In MC‐I, observed variation was greater within populations (69%) than among populations (31%), whereas in MC‐II, 61% of the variation was among populations and 39% within populations. This study evidenced that the two morphological categories correspond to distinct and reproductively isolated species and that floral traits reflect their breeding system, with allogamous plants in MC‐I and autogamous in MC‐II. Furthermore, MC‐II is unveiled as S. platycaule, a neglected taxon of Sisyrinchium in Brazil. The tools applied in this study were substantially able to check the identity of the two morphological categories as two different species and present the variation encountered in the taxa.     

Algorithmic approaches for identification of RNA editing sites.

Recently a number of groups have introduced computational methods for the detection of A-to-I RNA editing sites. These approaches have resulted in finding thousands of editing sites within the genomic repeats, as well as a few novel genetic recoding sites. We review these recent advancements, emphasizing the principles underlying the various methods used. Possible directions for extending these methods are discussed.     

Rigorous approaches to species delimitation have significant implications for African crocodilian systematics and conservation

Accurate species delimitation is a central assumption of biology that, in groups such as the Crocodylia, is often hindered by highly conserved morphology and frequent introgression. In Africa, crocodilian systematics has been hampered by complex regional biogeography and confounded taxonomic history. We used rigorous molecular and morphological species delimitation methods to test the hypothesis that the slender-snouted crocodile (Mecistops cataphractus) is composed of multiple species corresponding to the Congolian and Guinean biogeographic zones. Speciation probability was assessed by using 11 mitochondrial and nuclear genes, and cranial morphology for over 100 specimens, representing the full geographical extent of the species distribution. Molecular Bayesian and phylogenetic species delimitation showed unanimous support for two Mecistops species isolated to the Upper Guinean and Congo (including Lower Guinean) biomes that were supported by 13 cranial characters capable of unambiguously diagnosing each species. Fossil-calibrated phylogenetic reconstruction estimated that the species split ± 6.5–7.5 Ma, which is congruent with intraspecies divergence within the sympatric crocodile genus Osteolaemus and the formation of the Cameroon Volcanic Line. Our results underscore the necessity of comprehensive phylogeographic analyses within currently recognized taxa to detect cryptic species within the Crocodylia. We recommend that the community of crocodilian researchers reconsider the conceptualization of crocodilian species especially in the light of the conservation ramifications for this economically and ecologically important group.     

Multiphase morphospace saturation in cyrtocrinid crinoids

The study of the relationship between disparity (occupied morphospace) and diversity (number of taxa) through geological time represents a powerful tool in the macroevolutionary study of groups. In this contribution, this approach is applied for the first time to the cyrtocrinid crinoids, a major clade of mostly Mesozoic articulate crinoids also represented by rare Cenozoic forms (two extant taxa). The analysis of disparity identified two separate evolutionary radiations for cyrtocrinids with maximum morphospace exploration, one at the beginning of the evolutionary history of the group in the Pliensbachian and a second one between the Late Jurassic and Early Cretaceous. On the methodological level, the disparity measured both as total variance and as sum of ranges shows compatible results, with trends well coupled to the diversity curve indicating that, in cyrtocrinid crinoids, an increase or decrease in the number of taxa in the history of the clade corresponds a proportional increase and decrease also in the occupied morphospace. The curves obtained were interpreted in the light of the clade's phylogeny, major oceanographic events, newly available ecological niches and relative key innovations, which would be able to increase the fitness of the group. The group diversity was already in decline starting from the Aptian, and the mass extinction at the K‐PG boundary had no effect on the history of the clade. The results show once again the importance and potential of diversity/disparity studies when put into the light of palaeotectonic, palaeoecological and palaeoenvironmental factors.     

Ontogenic tracks and evolutionary vestiges in morphospace

Strombid shells were used to exemplify how to construct ontogenic tracks and evolutionary vestiges in morphological space (morphospace). Parameters in a mathematical model of shell form were used to construct morphospaces. Ontogenic information was mapped into these morphospaces to form 'tracks' Ontogenic tracks showed that the predominant trend of morphological evolution of strombid species consisted of an increase of vertical dimensions of whorls (apertures). Integrating information extracted from cladograms with ontogenic tracks in morphospace, 'evolutionary vestiges' were determined and used to infer and reconstruct ancestral shell forms.     

New approaches in first aid for cardiovascular patients]

Sudden cardiac arrest is a major problem of our society. Ventricular fibrillation strikes without any warning. It leads to unconsciousness and death occurs within minutes. Every year at least 100,000 people die from sudden cardiac arrest in Germany alone. The following article is concerned with how todays rescue system can be improved in order to increase survival rates. The time which passes between occurrence of the ventricular fibrillation and the therapeutic defibrillation plays a major role. It is being observed that decentralizing the rescue system is of great advantage. The idea of the "first responder", involving laymen, family members, and company paramedics, reduces the rescue time extraordinarily. The introduction of a digital emergency health record which provides the doctor with all the important data on the patient briefly seems to be of equal importance. Hereby, delays based on false information can be reduced to a minimum. Optimizing the equipment by means of implementing automatic procedures which enable the application by laymen is just as important. But the key to medical success appears to be educating and repeatedly training as many people as possible.     

How to fail at species delimitation

Species delimitation is the act of identifying species‐level biological diversity. In recent years, the field has witnessed a dramatic increase in the number of methods available for delimiting species. However, most recent investigations only utilize a handful (i.e. 2–3) of the available methods, often for unstated reasons. Because the parameter space that is potentially relevant to species delimitation far exceeds the parameterization of any existing method, a given method necessarily makes a number of simplifying assumptions, any one of which could be violated in a particular system. We suggest that researchers should apply a wide range of species delimitation analyses to their data and place their trust in delimitations that are congruent across methods. Incongruence across the results from different methods is evidence of either a difference in the power to detect cryptic lineages across one or more of the approaches used to delimit species and could indicate that assumptions of one or more of the methods have been violated. In either case, the inferences drawn from species delimitation studies should be conservative, for in most contexts it is better to fail to delimit species than it is to falsely delimit entities that do not represent actual evolutionary lineages.     

Biodiversity inhibits species' evolutionary responses to changing environments

Despite growing interplay between ecological and evolutionary studies, the question of how biodiversity influences evolutionary dynamics within species remains understudied. Here, using a classical model of phenotypic evolution in species occupying a patchy environment, but introducing global change affecting patch conditions, we show that biodiversity can inhibit species' evolution during global change. The presence of several species increases the chance that one or more species are pre-adapted to new conditions, which restricts the ecological opportunity for evolutionary responses in all the species. Consequently, environmental change tends to select for changes in species abundances rather than for changing phenotypes within each species. The buffering effects of species diversity that we describe might be one important but neglected explanation for widely observed niche conservatism in natural systems. Furthermore, the results show that attempts to understand biotic responses to environmental change need to consider both ecological and evolutionary processes in a realistically diverse setting.     

An empirical comparison of character‐based and coalescent‐based approaches to species delimitation in a young avian complex

The process of discovering species is a fundamental responsibility of systematics. Recently, there has been a growing interest in coalescent‐based methods of species delimitation aimed at objectively identifying species early in the divergence process. However, few empirical studies have compared these new methods with character‐based approaches for discovering species. In this study, we applied both a character‐based and a coalescent‐based approaches to delimit species in a closely related avian complex, the light‐vented/Taiwan bulbul (Pycnonotus sinensis/Pycnonotus taivanus). Population aggregation analyses of plumage, mitochondrial and 13 nuclear intron character data sets produced conflicting species hypotheses with plumage data suggesting three species, mitochondrial data suggesting two species, and nuclear intron data suggesting one species. Such conflict is expected among recently diverged species, and by integrating all sources of data, we delimited three species verified with independently congruent character evidence as well as a more weakly supported fourth species identified by a single character. Attempts to validate species hypothesis using Bayesian Phylogenetics and Phylogeography (BPP), a coalescent‐based method of species delimitation, revealed several issues that can seemingly affect statistical support for species recognition. We found that θ priors had a dramatic impact on speciation probabilities, with lower values consistently favouring splitting and higher values consistently favouring lumping. More resolved guide trees also resulted in overall higher speciation probabilities. Finally, we found suggestive evidence that BPP is sensitive to the divergent effects of nonrandom mating caused by intraspecific processes such as isolation‐with‐distance, and therefore, BPP may not be a conservative method for delimiting independently evolving population lineages. Based on these concerns, we questioned the reliability of BPP results and based our conclusions about species limits exclusively on character data.     

Rethinking species' ability to cope with rapid climate change

Ongoing climate change is assumed to be exceptional because of its unprecedented velocity. However, new geophysical research suggests that dramatic climatic changes during the Late Pleistocene occurred extremely rapid, over just a few years. These abrupt climatic changes may have been even faster than contemporary ones, but relatively few continent‐wide extinctions of species have been documented for these periods. This raises questions about the ability of extant species to adapt to ongoing climate change. We propose that the advances in geophysical research challenge current views about species' ability to cope with climate change, and that lessons must be learned for modelling future impacts of climate change on species.