Biomedical subjects

Vladimir Makarenkov

Publications and source records attributed to Vladimir Makarenkov.

8 recordsLinked to original sources

PubMed2024

Assessing the emergence time of SARS-CoV-2 zoonotic spillover.

Understanding the evolution of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and its relationship to other coronaviruses in the wild is crucial for preventing future virus outbreaks. While the origin of the SARS-CoV-2 pandemic remains uncertain, mounting evidence suggests the direct involvement of the bat and pangolin coronaviruses in the evolution of the SARS-CoV-2 genome. To unravel the early days of a probable zoonotic spillover event, we analyzed genomic data from various coronavirus strains from both human and wild hosts. Bayesian phylogenetic analysis was performed using multiple datasets, using strict and relaxed clock evolutionary models to estimate the occurrence times of key speciation, gene transfer, and recombination events affecting the evolution of SARS-CoV-2 and its closest relatives. We found strong evidence supporting the presence of temporal structure in datasets containing SARS-CoV-2 variants, enabling us to estimate the time of SARS-CoV-2 zoonotic spillover between August and early October 2019. In contrast, datasets without SARS-CoV-2 variants provided mixed results in terms of temporal structure. However, they allowed us to establish that the presence of a statistically robust clade in the phylogenies of gene S and its receptor-binding (RBD) domain, including two bat (BANAL) and two Guangdong pangolin coronaviruses (CoVs), is due to the horizontal gene transfer of this gene from the bat CoV to the pangolin CoV that occurred in the middle of 2018. Importantly, this clade is closely located to SARS-CoV-2 in both phylogenies. This phylogenetic proximity had been explained by an RBD gene transfer from the Guangdong pangolin CoV to a very recent ancestor of SARS-CoV-2 in some earlier works in the field before the BANAL coronaviruses were discovered. Overall, our study provides valuable insights into the timeline and evolutionary dynamics of the SARS-CoV-2 pandemic.

Animals↗

PubMed2006

Using clustering techniques to improve hit selection in high-throughput screening.

A typical modern high-throughput screening (HTS) operation consists of testing thousands of chemical compounds to select active ones for future detailed examination. The authors describe 3 clustering techniques that can be used to improve the selection of active compounds (i.e., hits). They are designed to identify quality hits in the observed HTS measurements. The considered clustering techniques were first tested on simulated data and then applied to analyze the assay inhibiting Escherichia coli dihydrofo-late reductase produced at the HTS laboratory of McMaster University.

Cluster Analysis↗

PubMed2006

HTS-Corrector: software for the statistical analysis and correction of experimental high-throughput screening data.

MOTIVATION: High-throughput screening (HTS) plays a central role in modern drug discovery, allowing for testing of >100,000 compounds per screen. The aim of our work was to develop and implement methods for minimizing the impact of systematic error in the analysis of HTS data. To the best of our knowledge, two new data correction methods included in HTS-Corrector are not available in any existing commercial software or freeware. RESULTS: This paper describes HTS-Corrector, a software application for the analysis of HTS data, detection and visualization of systematic error, and corresponding correction of HTS signals. Three new methods for the statistical analysis and correction of raw HTS data are included in HTS-Corrector: background evaluation, well correction and hit-sigma distribution procedures intended to minimize the impact of systematic errors. We discuss the main features of HTS-Corrector and demonstrate the benefits of the algorithms.

Algorithms↗

PubMed2005

Statistical analysis of systematic errors in high-throughput screening.

High-throughput screening (HTS) is an efficient technology for drug discovery. It allows for screening of more than 100,000 compounds a day per screen and requires effective procedures for quality control. The authors have developed a method for evaluating a background surface of an HTS assay; it can be used to correct raw HTS data. This correction is necessary to take into account systematic errors that may affect the procedure of hit selection. The described method allows one to analyze experimental HTS data and determine trends and local fluctuations of the corresponding background surfaces. For an assay with a large number of plates, the deviations of the background surface from a plane are caused by systematic errors. Their influence can be minimized by the subtraction of the systematic background from the raw data. Two experimental HTS assays from the ChemBank database are examined in this article. The systematic error present in these data was estimated and removed from them. It enabled the authors to correct the hit selection procedure for both assays.

Algorithms↗

PubMed2004

A weighted least-squares approach for inferring phylogenies from incomplete distance matrices.

MOTIVATION: The problem of phylogenetic inference from datasets including incomplete or uncertain entries is among the most relevant issues in systematic biology. In this paper, we propose a new method for reconstructing phylogenetic trees from partial distance matrices. The new method combines the usage of the four-point condition and the ultrametric inequality with a weighted least-squares approximation to solve the problem of missing entries. It can be applied to infer phylogenies from evolutionary data including some missing or uncertain information, for instance, when observed nucleotide or protein sequences contain gaps or missing entries. RESULTS: In a number of simulations involving incomplete datasets, the proposed method outperformed the well-known Ultrametric and Additive procedures. Generally, the new method also outperformed all the other competing approaches including Triangle and Fitch which is the most popular least-squares method for reconstructing phylogenies. We illustrate the usefulness of the introduced method by analyzing two well-known phylogenies derived from complete mammalian mtDNA sequences. Some interesting theoretical results concerning the NP-hardness of the ordinary and weighted least-squares fitting of a phylogenetic tree to a partial distance matrix are also established. AVAILABILITY: The T-Rex package including this method is freely available for download at http://www.info.uqam.ca/~makarenv/trex.html

Algorithms↗

PubMed2004

From a phylogenetic tree to a reticulated network.

In many phylogenetic problems, assuming that species have evolved from a common ancestor by a simple branching process is unrealistic. Reticulate phylogenetic models, however, have been largely neglected because the concept of reticulate evolution have not been supported by using appropriate analytical tools and software. The reticulate model can adequately describe such complicated mechanisms as hybridization between species or lateral gene transfer in bacteria. In this paper, we describe a new algorithm for inferring reticulate phylogenies from evolutionary distances among species. The algorithm is capable of detecting contradictory signals encompassed in a phylogenetic tree and identifying possible reticulate events that may have occurred during evolution. The algorithm produces a reticulate phylogeny by gradually improving upon the initial solution provided by a phylogenetic tree model. The new algorithm is compared to the popular SplitsGraph method in a reanalysis of the evolution of photosynthetic organisms. A computer program to construct and visualize reticulate phylogenies, called T-Rex (Tree and Reticulogram Reconstruction), is available to researchers at the following URL: www.fas.umontreal.ca/biol/casgrain/en/labo/t-rex.

Algorithms↗

PubMed2003

Incomplete distance matrices, supertrees and bat phylogeny.

In this paper, we evaluate the relative performance of competing approaches for estimating phylogenies from incomplete distance matrices. The direct approach proceeds with phylogenetic reconstruction while ignoring missing cells, whereas the indirect approach proceeds by estimating the missing distances prior to phylogenetic analysis. Two distinct indirect procedures based on the ultrametric inequality and the four-point condition are further compared. Using simulations, we show that more reliable results are obtained when such indirect methods are used. Expectedly, the phylogenies become less accurate as the percentage of missing cells increases, but combining different estimation methods greatly improves the accuracy. An application to bat phylogeny confirms the results obtained in the simulation study and illustrates the effect of missing distances in the construction of supertrees.

Animals↗

PubMed2002

Reconstruction of biogeographic and evolutionary networks using reticulograms.

A reticulogram is a general network capable of representing a reticulate evolutionary structure. It is particularly useful for portraying relationships among organisms that may be related in a nonunique way to their common ancestor - relationships that cannot be represented by a dendrogram or a phylogenetic tree. We propose a new method for constructing reticulograms that represent a given distance matrix. Reticulate evolution applies first to phylogenetic problems; it has been found in nature, for example, in the within-species microevolution of eukaryotes and in lateral gene transfer in bacteria. In this paper, we propose a new method for reconstructing reticulation networks and we develop applications of the reticulate evolution model to ecological biogeographic, population microevolutionary, and hybridization problems. The first example considers a spatially constrained reticulogram representing the postglacial dispersal of freshwater fishes in the Québec peninsula; the reticulogram provides a better model of postglacial dispersal than does a tree model. The second example depicts the morphological similarities among local populations of muskrats in a river valley in Belgium; adding supplementary branches to a tree depicting the river network leads to a better representation of the morphological distances among local populations of muskrats than does a tree structure. A third example involves hybrids between plants of the genus Aphelandra.

Algorithms↗