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Results for “Lineage tree reconstruction”

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At least 19 recordsLinked to original sources

PubMed2026

Bayesian inference of lineage trees by joint analysis of single-cell multimodal lineage-tracing data with BiLinT.

The advent of single-cell lineage-tracing technologies has enabled the simultaneous profiling of gene expression and lineage barcodes. However, accurate, high-resolution reconstruction of cell lineage trees remains challenging because most existing approaches treat these modalities separately and therefore fail to fully exploit their complementary information. Here we present BiLinT, a Bayesian framework that jointly models multimodal single-cell lineage-tracing data for lineage tree reconstruction. BiLinT integrates barcode evolution (a continuous-time Markov chain) with gene expression dynamics (an Ornstein-Uhlenbeck process) within a unified probabilistic model. Across synthetic and real data sets, BiLinT provides accurate lineage-tree reconstruction and reveals differentiation-associated clonal structure and developmental fate biases.

Journal Article↗

PubMed2025

Paired Single-Cell Transcriptome and DNA Barcode Detection in Zebrafish Using ScarTrace.

ScarTrace is a CRISPR/Cas9-based genetic lineage tracing method that allows for uniquely barcoding the DNA of single cells at a target GFP sequence during developing zebrafish embryos. Single cells from barcoded adult zebrafish can be isolated from various tissues (e.g., marrow, brain, eyes, fins), and their transcriptome and barcode sequences are captured by single-cell cDNA amplification and genomic DNA nested PCR, respectively. Computationally, cell type and barcode identification permit clone tracing and lineage tree reconstruction of tissues to unravel fate decisions during embryogenesis.

Animals↗

PubMed1997

Evolution and phylogeny of the Diptera: a molecular phylogenetic analysis using 28S rDNA sequences.

Portions of the large ribosomal subunit RNA gene (28S rDNA) encompassing the D1 and the D7 region were obtained from 16 dipteran species and families to reconstruct early phylogenetic events in the order Diptera. For outgroup comparison, the corresponding sequences were used from representative taxa of the Siphonaptera, Mecoptera, and Lepidoptera. A subset of 488 unambiguously alignable sites was analyzed with respect to important sequence evolution parameters. We found (1) sequence variability is significantly higher in double-stranded sites than in single-stranded sites, (2) transitions are close to saturation in most pairwise sequence comparisons, (3) significant substitution rate heterogeneity exists across sites, and (4) significant substitution rate heterogeneity exists among lineages. Tree reconstruction was carried out with the neighbor joining, maximum parsimony, and maximum likelihood methods. Four major subgroups are consistently and robustly supported: the Brachycera, the Culicomorpha, the Tipulomorpha sensu stricto, and the hitherto controversial Bibionomorpha sensu lato, which includes the families Sciaridae, Mycetophilidae, Cecidomyiidae, Bibionidae, Scatopsidae, and Anisopodidae. The phylogenetic relationships within or among these subclades and the positions of the families Psychodidae and Trichoceridae were not robustly resolved. These results support the view that the mouthparts of extant dipteran larvae evolved from a derived ground state characterized by subdivided and obliquely moving mandibles. Furthermore, sequence divergence and the paleontological record consistently indicate that a period of rapid cladogenesis gave rise to the major dipteran subgroups.

Animals↗

PubMed2003

Monitoring neural progenitor fate through multiple rounds of division in an intact vertebrate brain.

The behaviour of neural progenitors in the intact vertebrate brain and spinal cord is poorly understood, chiefly because of the inaccessibility and poor optical qualities inherent in many model systems. To overcome these problems we have studied the optically superior brain of the zebrafish embryo and have monitored the in vivo behaviour of fluorescently labelled neural progenitors and their daughter cells throughout a substantial period of hindbrain development. We find the majority (84%) of hindbrain neurons are born from progenitor divisions that generate two neurons and 68% of reconstructed lineage trees contained no asymmetric stem cell-like divisions. No progenitors divided in the manner expected of a classic stem cell; i.e. one that repeatedly self-renews and generates a differentiated cell type by asymmetric division. We also analysed the orientation of progenitor divisions relative to the plane of the ventricular zone (VZ) and find that this does not correlate with the fate of the daughter cells. Our results suggest that in this vertebrate system the molecular determinants that control whether a cell will become a neuron are usually not linked to a mechanism that generates asymmetric divisions.

Animals↗

PubMed2005

Genomic variability within an organism exposes its cell lineage tree.

What is the lineage relation among the cells of an organism? The answer is sought by developmental biology, immunology, stem cell research, brain research, and cancer research, yet complete cell lineage trees have been reconstructed only for simple organisms such as Caenorhabditis elegans. We discovered that somatic mutations accumulated during normal development of a higher organism implicitly encode its entire cell lineage tree with very high precision. Our mathematical analysis of known mutation rates in microsatellites (MSs) shows that the entire cell lineage tree of a human embryo, or a mouse, in which no cell is a descendent of more than 40 divisions, can be reconstructed from information on somatic MS mutations alone with no errors, with probability greater than 99.95%. Analyzing all approximately 1.5 million MSs of each cell of an organism may not be practical at present, but we also show that in a genetically unstable organism, analyzing only a few hundred MSs may suffice to reconstruct portions of its cell lineage tree. We demonstrate the utility of the approach by reconstructing cell lineage trees from DNA samples of a human cell line displaying MS instability. Our discovery and its associated procedure, which we have automated, may point the way to a future "Human Cell Lineage Project" that would aim to resolve fundamental open questions in biology and medicine by reconstructing ever larger portions of the human cell lineage tree.

Animals↗

PubMed1992

Statistical method for estimating the standard errors of branch lengths in a phylogenetic tree reconstructed without assuming equal rates of nucleotide substitution among different lineages.

A statistical method is developed for estimating the standard errors of branch lengths in a phylogenetic tree reconstructed without assuming equal rates of nucleotide substitution among different lineages. This method can be easily used for testing whether the length of an interior branch in a reconstructed tree is positive, i.e., whether the topology of the tree is correct. Computer simulations indicate that this method is appropriate for a statistical test. As an example, this method is applied to phylogenetic trees reconstructed for the four hominoid species: human, chimpanzee, gorilla, and orangutan. The results obtained show that the present method provides a powerful statistical test.

Animals↗

PubMed1998

Phylogeny of nematode-trapping fungi based on 18S rDNA sequences.

The small subunit (SSU) ribosomal DNA (18S rDNA) from 15 species of nematode-trapping fungi and closely related non-parasitic species were sequenced. Phylogenetic analysis indicated that species within the genera of Arthrobotrys, Dactylaria, Dactylella, Monacrosporium and Duddingtonia formed a monophyletic and isolated clade among an unresolved cluster of apothecial ascomycetes. The phylogenetic patterns within this clade were not concordant with the morphology of the conidia nor the conidiophores, but rather with that of the infection structures. The results from the different methods of tree reconstruction supported three lineages; the species having constricting rings, the non-parasitic species and the species having various adhesive structures (nets, hyphae, knobs and non-constricting rings) to infect nematodes.

Animals↗

PubMed2006

In situ origin of deep rooting lineages of mitochondrial Macrohaplogroup 'M' in India.

BACKGROUND: Macrohaplogroups 'M' and 'N' have evolved almost in parallel from a founder haplogroup L3. Macrohaplogroup N in India has already been defined in previous studies and recently the macrohaplogroup M among the Indian populations has been characterized. In this study, we attempted to reconstruct and re-evaluate the phylogeny of Macrohaplogroup M, which harbors more than 60% of the Indian mtDNA lineage, and to shed light on the origin of its deep rooting haplogroups. RESULTS: Using 11 whole mtDNA and 2231 partial coding sequence of Indian M lineage selected from 8670 HVS1 sequences across India, we have reconstructed the tree including Andamanese-specific lineage M31 and calculated the time depth of all the nodes. We defined one novel haplogroup M41, and revised the classification of haplogroups M3, M18, and M31. CONCLUSION: Our result indicates that the Indian mtDNA pool consists of several deep rooting lineages of macrohaplogroup 'M' suggesting in-situ origin of these haplogroups in South Asia, most likely in the India. These deep rooting lineages are not language specific and spread over all the language groups in India. Moreover, our reanalysis of the Andamanese-specific lineage M31 suggests population specific two clear-cut subclades (M31a1 and M31a2). Onge and Jarwa share M31a1 branch while M31a2 clade is present in only Great Andamanese individuals. Overall our study supported the one wave, rapid dispersal theory of modern humans along the Asian coast.

DNA, Mitochondrial↗

PubMed2006

Multi-character perspectives on the evolution of intraspecific differentiation in a neotropical hylid frog.

BACKGROUND: Multi-character empirical studies are important contributions to our understanding of the process of speciation. The relatively conserved morphology of, and importance of the mate recognition system in anurans, combined with phylogenetic tools, provide an opportunity to address predictions about the relative role of each in the process of speciation. We examine the relationship among patterns of variation in morphology, call characters, and 16S gene sequences across seven populations of a neotropical hylid frog, Hyla leucophyllata, to infer their relative importance in predicting the early stages of population differentiation. RESULTS: Multivariate analyses demonstrate that both morphological and call characteristics were significantly variable among populations, characterized by significantly lower intra-population dispersion in call space than morphological space, and significantly greater among-population variation in call structure. We found lack of concordance between a 16S DNA phylogeny of Hyla leucophyllata and the significant population-level differentiation evident in both external morphology and male advertisement call. Comparisons of the reconstructed gene trees to simulated lineages support the notion that variation in call cannot be simply explained by population history. CONCLUSION: Discordance among traits may reflect sampling biases (e.g. single genetic marker effects), or imply a decoupling of evolution of different suites of characters. Diagnostic differences among populations in call structure possibly reflect local selection pressures presented by different heterospecific calling assemblages and may serve as a precursor of species-wide differentiation. Differentiation among populations in morphology may be due to ecophenotypic variation or to diversifying selection on body size directly, or on frequency attributes of calls (mediated by female choice) that show a strong relationship to body size.

Animals↗

PubMed2006

A computer simulation analysis of the accuracy of partial genome sequencing and restriction fragment analysis in the reconstruction of phylogenetic relationships.

Partial genome sequencing (PGS) and restriction fragment analysis (RFA) are used frequently in molecular epidemiologic investigations. The relative accuracy of PGS and RFA in phylogenetic reconstruction has not been assessed. In this study, 32 model phylogenetic trees with 16 extant lineages were generated, for which DNA sequences were simulated under varying conditions of genome length, nucleotide substitution rate, and between-site substitution rate variation. Genotyping using PGS and RFA was simulated. The effect of tree structure (stemminess, imbalance, lineage variation) on the accuracy of phylogenetic reconstruction (topological and branch length similarity) was evaluated. Overall, PGS was more accurate than RFA. The accuracy of PGS increased with increasing sequence length. The accuracy of RFA increased with the number of restriction enzymes used. In fragment size comparison, the Dice and Nei-Li algorithms differed little, with both more accurate than the Fragment Size Distribution algorithm. For RFA, higher tree stemminess and longer genome length were associated with higher topological accuracy, whereas lower tree stemminess and lower substitution rates were associated with higher branch length accuracy. For PGS, lower tree imbalance was associated with higher topological accuracy, whereas lower tree stemminess, higher substitution rate, and lower between-site substitution rate variation were associated with higher branch length accuracy. RFA had higher topological accuracy than PGS only for the shortest sequence length (200 bps) at a low substitution rate, high tree stemminess, and long genome length. PGS had equal or higher accuracy in branch length reconstruction than RFA under all conditions investigated. Thus, partial genome sequencing is recommended over restriction fragment analysis for conditions within the parameter space examined.

Computational Biology↗

PubMed2004

Nuclear corroboration of DNA-DNA hybridization in deep phylogenies of hummingbirds, swifts, and passerines: the phylogenetic utility of ZENK (ii).

This paper documents the phylogenetic utility of ZENK at the avian intra-ordinal level using hummingbirds, swifts, and passerines as case studies. ZENK sequences (1.7 kb) were used to reconstruct separate gene trees containing the major lineages of each group, and the three trees were examined for congruence with existing DNA-DNA hybridization trees. The results indicate both that ZENK is an appropriate nuclear marker for resolving relationships deep in the avian tree, and that many relationships within these three particular groups are congruent among the different datasets. Specifically, within hummingbirds there was topological agreement that the major hummingbird lineages diverged in a graded manner from the "hermits," to the "mangoes," to the "coquettes," to the "emeralds," and finally to a sister relationship between the "mountain-gems" and the "bees." Concerning swifts, the deepest divergences were congruent: treeswifts (Hemiprocnidae) were sister to the typical swifts (Apodidae), and the subfamily Apodinae was monophyletic relative to Cypseloidinae. Within Apodinae, however, were short, unresolved branches among the swiftlets, spinetails, and more typical swifts; a finding which coincides with other datasets. Within passerine birds, there was congruent support for monophyly of sub-oscines and oscines, and within sub-oscines, for monophyly of New World groups relative to the Old World lineages. New World sub-oscines split into superfamilies Furnaroidea and Tyrannoidea, with the Tyrannoid relationships completely congruent among ZENK and DNA-DNA hybridization trees. Within Furnaroidea, however, there was some incongruence regarding the positions of Thamnophilidae and Formicariidae. Concerning oscine passerines, both datasets showed a split between Corvida and Passerida and confirmed the traditional membership of passerid superfamilies Muscicapoidea and Passeroidea. Monophyly of Sylvioidea, however, remained uncertain, as did the relationships among the superfamiles themselves. These results are strikingly similar to other recent findings and indicative of continuing uncertainty about the higher level relationships of oscine passerines.

Animals↗

PubMed2001

[Genetic relationship among four Yunnan populations revealed by sequence of mtDNA D-loop].

mtDNA D-loop noncoding region 16048-16569 and the following 1-41 (563 bp) in 99 individuals of four Yunnan ethnic minorities (Dai, Wa, Lahu and Tibetan) were sequenced and then a phylogenetic tree was reconstructed by Neighbor-Joining method. These 99 mtDNA lineages were classified into 3 genotype groups in the tree. All lineages with 9 bp deletion in the COII/tRAN(Lys) intergenic region were clustered in group I, some individuals of Dai, Lahu, Wa and only 2 Tibetan individuals clustered in group II, individuals of all four populations were included in group III. A phylogenetic tree of the four populations was constructed by NJ method on the basis of estimate of net genetic distance among them. Our results showed, the genetic distance among Dai, Wa and Lahu is very close, but far from Tibetan, their genetic distance is similar to their geographic distance. Although both as descendants of ancient Di-Qiang tribe in history and speaking similar language, Lahu and Tibetan are not closely related. This result indicates that there are different origins of these two populations.

China↗

PubMed2025

LINNAEUS: Simultaneous Single-Cell Lineage Tracing and Cell Type Identification.

A key goal of biology is to understand the origin of the many cell types that can be observed during diverse processes such as development, regeneration, and disease. Single-cell RNA-sequencing (scRNA-seq) is commonly used to identify cell types in a tissue or organ. However, organizing the resulting taxonomy of cell types into lineage trees to understand the origins of cell states and relationships between cells remains challenging. Here we present LINNAEUS (Spanjaard et al, Nat Biotechnol 36:469-473. https://doi.org/10.1038/nbt.4124 , 2018; Hu et al, Nat Genet 54:1227-1237. https://doi.org/10.1038/s41588-022-01129-5 , 2022) (LINeage tracing by Nuclease-Activated Editing of Ubiquitous Sequences)-a strategy for simultaneous lineage tracing and transcriptome profiling in thousands of single cells. By combining scRNA-seq with computational analysis of lineage barcodes, generated by genome editing of transgenic reporter genes, LINNAEUS can be used to reconstruct organism-wide single-cell lineage trees. LINNAEUS provides a systematic approach for tracing the origin of novel cell types, or known cell types under different conditions.

Single-Cell Analysis↗

PubMed2004

Lineage specificity of gene expression patterns.

The hematopoietic system offers many advantages as a model for understanding general aspects of lineage choice and specification. Using oligonucleotide microarrays, we compared gene expression patterns of multiple purified hematopoietic cell populations, including neutrophils, monocytes, macrophages, resting, centrocytic, and centroblastic B lymphocytes, dendritic cells, and hematopoietic stem cells. Some of these cells were studied under both resting and stimulated conditions. We studied the collective behavior of subsets of genes derived from the Biocarta database of functional pathways, hand-tuned groupings of genes into broad functional categories based on the Gene Ontology database, and the metabolic pathways in the Kyoto Encyclopedia of Genes and Genomes database. Principal component analysis revealed strikingly pervasive differences in relative levels of gene expression among cell lineages that involve most of the subsets examined. These results indicate that many processes in these cells behave differently in different lineages. Much of the variation among lineages was captured by the first few principal components. Principal components biplots were found to provide a convenient visual display of the contributions of the various genes within the subsets in lineage discrimination. Moreover, by applying tree-constructing methodologies borrowed from phylogenetics to the expression data from differentiated cells and stem cells, we reconstructed a tree of relationships that resembled the established hematopoietic program of lineage development. Thus, the mRNA expression data implicitly contained information about developmental relationships among cell types.

Cell Lineage↗

PubMed2005

Nuclear ribosomal DNA sequence variation and evolution of spotted marsh-orchids (Dactylorhiza maculata group).

Sequences of both internal and external transcribed spacers of nuclear ribosomal DNA were sequenced for four species belonging to the Dactylorhiza maculata group or "spotted marsh-Orchids". These four species are D. fuchsii, D. saccifera, D. foliosa, and D. maculata. Extensive nuclear ribosomal DNA polymorphism was uncovered within the diploid D. fuchsii and the putative autotetraploid D. maculata. Within the phylogenetic trees reconstructed using parsimony and Bayesian analyses, four main lineages (A, B, C, and D) were well supported. While D. saccifera, D. maculata, and D. foliosa were confined to clades B, C, and D, respectively, D. fuchsii accessions were spread over three clades (A, B, and C). Lineage C, which included accessions of the diploid D. fuchsii and the tetraploid D. maculata, was closely related to the lineage of D. foliosa (lineage D), an endemic diploid species from Madeira. Moreover, intra-individual polymorphism was found within accessions of D. maculata, D. fuchsii, and D. saccifera. It is shown that in some instances two lineages, contributed to the observed intra-individual polymorphism (C and A in D. maculata, A and B in D. fuchsii and D. saccifera). Evolutionary scenarios leading to this extensive nuclear ribosomal DNA polymorphism are discussed in the light of results from maternally inherited chloroplast DNA markers and an autopolyploid origin of D. maculata from a D. foliosa-like ancestor is postulated.

Animals↗

PubMed2026

LAML-Pro: joint maximum likelihood inference of cell genotypes and cell lineage trees.

MOTIVATION: Recent dynamic lineage tracing technologies use genome editing to induce heritable mutations, or edits, that accumulate across successive cell divisions. These edits are measured using single-cell sequencing or imaging, providing data to reconstruct cell lineages at single-cell resolution. Current computational approaches to infer cell lineage trees, or phylogenies, from these data perform two separate steps: (i) Identify each cell's edits (genotype) from the raw sequencing or imaging data; (ii) Infer a cell lineage tree from the cell genotypes. However, genotyping cells is an inexact process and genotype errors can yield an inaccurate lineage tree. For example, using fluorescence based-imaging to measure edits results in a high fraction (≈25%-50%) of uncertain or erroneous genotypes. RESULTS: We introduce Lineage Analysis via Maximum Likelihood with PRobabilistic Observations (LAML-Pro), an algorithm that jointly infers cell genotypes and a cell lineage tree. LAML-Pro is based on the Probabilistic Mixed-type Missing Observation (PMMO) model, which we derive to describe both the genome editing and genotype observation processes. LAML-Pro constructs lineage trees from thousands of cells in under an hour by leveraging the sparsity of transitions under the PMMO model. On simulated data, we demonstrate that LAML-Pro corrects genotype errors and infers substantially more accurate trees than existing methods which are vulnerable to genotype errors. Applied to data from two recent imaging-based lineage tracing systems, LAML-Pro reduces genotype errors by 5-fold and produces more spatially coherent lineage trees compared to existing methods. AVAILABILITY AND IMPLEMENTATION: LAML-Pro is implemented in C++ and is available as both a command-line interface and as a Python library at: github.com/raphael-group/LAML-Pro.

Cell Lineage↗

PubMed2026

LAML-Pro: Joint Maximum Likelihood Inference of Cell Genotypes and Cell Lineage Trees.

MOTIVATION: Recent dynamic lineage tracing technologies use genome editing to induce heritable mutations, or edits, that accumulate across successive cell divisions. These edits are measured using single-cell sequencing or imaging, providing data to reconstruct cell lineages at single-cell resolution. Current computational approaches to infer cell lineage trees, or phylogenies, from these data perform two separate steps: (1) Identify each cell's edits (genotype) from the raw sequencing or imaging data; (2) Infer a cell lineage tree from the cell genotypes. However, genotyping cells is an inexact process and genotype errors can yield an inaccurate lineage tree. For example, using fluorescence based-imaging to measure edits results in a high fraction (≈ 25-50%) of uncertain or erroneous genotypes. RESULTS: We introduce Lineage Analysis via Maximum Likelihood with PRobabilistic Observations (LAML-Pro), an algorithm that jointly infers cell genotypes and a cell lineage tree. LAML-Pro is based on the Probabilistic Mixed-type Missing Observation (PMMO) model, which we derive to describe both the genome editing and genotype observation processes. LAML-Pro constructs lineage trees from thousands of cells in under an hour by leveraging the sparsity of transitions under the PMMO model. On simulated data, we demonstrate that LAML-Pro corrects genotype errors and infers substantially more accurate trees than existing methods which are vulnerable to genotype errors. Applied to data from two recent imaging-based lineage tracing systems, LAML-Pro reduces genotype errors by 5-fold and produces more spatially coherent lineage trees compared to existing methods. AVAILABILITY AND IMPLEMENTATION: LAML-Pro is freely available at: github.com/raphael-group/LAML-Pro.

Journal Article↗

PubMed2002

Inferring genome trees by using a filter to eliminate phylogenetically discordant sequences and a distance matrix based on mean normalized BLASTP scores.

Darwin's paradigm holds that the diversity of present-day organisms has arisen via a process of genetic descent with modification, as on a bifurcating tree. Evidence is accumulating that genes are sometimes transferred not along lineages but rather across lineages. To the extent that this is so, Darwin's paradigm can apply only imperfectly to genomes, potentially complicating or perhaps undermining attempts to reconstruct historical relationships among genomes (i.e., a genome tree). Whether most genes in a genome have arisen via treelike (vertical) descent or by lateral transfer across lineages can be tested if enough complete genome sequences are used. We define a phylogenetically discordant sequence (PDS) as an open reading frame (ORF) that exhibits patterns of similarity relationships statistically distinguishable from those of most other ORFs in the same genome. PDSs represent between 6.0 and 16.8% (mean, 10.8%) of the analyzable ORFs in the genomes of 28 bacteria, eight archaea, and one eukaryote (Saccharomyces cerevisiae). In this study we developed and assessed a distance-based approach, based on mean pairwise sequence similarity, for generating genome trees. Exclusion of PDSs improved bootstrap support for basal nodes but altered few topological features, indicating that there is little systematic bias among PDSs. Many but not all features of the genome tree from which PDSs were excluded are consistent with the 16S rRNA tree.

Databases, Protein↗