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Sudhir Kumar

Publications and source records attributed to Sudhir Kumar.

At least 19 recordsLinked to original sources
PubMed2026

Phylogenomic subsampling and upsampling for efficient evolutionary analyses of big data.

Long runtimes, high memory demands, and reliance on high-performance computing impede phylogenomic analyses. We review a scalable phylogenomic subsampling with upsampling (PSU) framework to address this challenge, which reduces runtime and memory requirements by orders of magnitude. In PSU, small subsamples of sites from a concatenated alignment are analyzed, which are expanded by upsampling before inference, and the resulting inferences are aggregated to obtain evolutionary estimates. PSU harnesses the fact that the computational cost of maximum likelihood analysis is strongly influenced by the number of distinct site patterns in the concatenated alignment, whereas statistical power depends primarily on the amount of evolutionary information represented by the total number of sites and substitutions. By reducing the former while restoring the latter through upsampling, PSU can approximate many full-alignment analyses at substantially lower computational cost. Analysis of simulated and empirical datasets shows that PSU can accurately estimate bootstrap support values, select the optimal substitution model, test evolutionary hypotheses, and infer branch lengths, divergence times, and associated uncertainty measures. PSU also provides distributions of inferred clade support across independent subsamples, enabling detection of conflicting phylogenetic signals that may remain hidden in conventional bootstrap analysis of concatenated alignments. Automated tuning of subsample size, the number of subsamples, and the number of upsampling replicates make PSU practical. We suggest that PSU is a general approach for scalable phylogenomic inference using a broad range of statistical methods. By enabling analyses of genome-scale alignments on commodity hardware, PSU broadens research access and reduces environmental and infrastructural costs of big-data phylogenomics.

Phylogeny↗
PubMed2026

Phylogenomic subsampling and upsampling for efficient evolutionary analyses of big data.

Long runtimes, high memory demands, and reliance on high-performance computing impede phylogenomic analyses. We review a scalable phylogenomic subsampling with upsampling (PSU) framework, in which small subsamples of sites from a concatenated alignment are expanded by upsampling before inference, and the resulting analyses are then aggregated to obtain evolutionary estimates. PSU harnesses the fact that the computational cost of maximum likelihood analysis is strongly influenced by the number of distinct site patterns in the concatenated alignment, whereas statistical power depends primarily on the amount of evolutionary information represented by the total number of sites and substitutions. By reducing the former while restoring the latter through upsampling, PSU can approximate many full-data analyses at substantially lower computational cost. Analysis of simulated and empirical datasets shows that PSU can accurately estimate bootstrap support values, select the optimal substitution model, test evolutionary hypotheses, and infer branch lengths, divergence times, and associated uncertainty measures, while reducing runtime and memory requirements by orders of magnitude. PSU also provides distributions of inferred clade support across independent subsamples, enabling detection of conflicting phylogenetic signals that may remain hidden in conventional bootstrap analysis. Automated tuning of subsample size, the number of subsamples, and the number of upsampling replicates make PSU practical across diverse datasets. We suggest that PSU is a general strategy for scalable phylogenomic inference using a broad range of statistical methods. By enabling analyses of genome-scale alignments on commodity hardware, PSU broadens research access and reduces environmental and infrastructural costs of big-data phylogenomics.

confidence limits↗
PubMed2026

Treemble: a graphical tool to generate Newick strings from phylogenetic tree images.

SUMMARY: Phylogenetic trees are ubiquitous and central to biology, but most published trees are available only as visual diagrams and not in the machine-readable Newick format. There are, thus, thousands of published trees in the scientific literature that are unavailable for follow-up analyses, comparisons, and supertree construction. Experts can easily read such diagrams, but the manual construction of a Newick string from a diagram is laborious, error-prone, and time-consuming. Previous attempts to semi-automate the reading of tree images relied on image processing techniques. These often encounter difficulties as typical published tree diagrams contain various graphical elements and annotations that overlap the branches, such as error bars on internal nodes. Here we introduce Treemble, a user-friendly desktop application for generating Newick strings from tree images. The user simply clicks to mark node locations, assisted by a deep learning-based node detection tool, and Treemble algorithmically assembles the tree from the node coordinates alone. Treemble also facilitates the automatic reading of tip name labels and can be used for both rectangular and circular trees. AVAILABILITY AND IMPLEMENTATION: Treemble is a native desktop application for macOS and Windows and is freely available, with documentation, at treemble.org. Source code is available at github.com/John-Allard/Treemble. The trained node detection model is available at huggingface.co/John-Allard/treemble-1.

Phylogeny↗
PubMed2025

MyESL: A Software for Evolutionary Sparse Learning in Molecular Phylogenetics and Genomics.

Evolutionary sparse learning uses supervised machine learning to build evolutionary models where genomic sites loci are parameters. It uses the Least Absolute Shrinkage and Selection Operator with bi-level sparsity to connect a specific phylogenetic hypothesis with sequence variation across genomic loci. The MyESL software addresses the need for open-source tools to perform evolutionary sparse learning analyses, offering features to preprocess input phylogenomic alignments, post-process output models to generate molecular evolutionary metrics, and make Least Absolute Shrinkage and Selection Operator regression adaptable and efficient for phylogenetic trees and alignments. The core of MyESL, which constructs models with logistic regressions using bi-level sparsity, is written in C++. Its input data preprocessing and result post-processing tools are developed in Python. Compared to other tools, MyESL is more computationally efficient and provides evolution-friendly inputs and outputs. These features have already enabled the use of MyESL in two phylogenomic applications, one to identify outlier sequences and fragile clades in inferred phylogenies and another to build genetic models of convergent traits. In addition to the use in a Python environment, MyESL is available as a standalone executable compatible across multiple platforms, which can be directly integrated into scripts and third-party software. The source code, executable, and documentation for MyESL are openly accessible at https://github.com/kumarlabgit/MyESL.

Phylogeny↗
PubMed2006

Evolutionary anatomies of positions and types of disease-associated and neutral amino acid mutations in the human genome.

BACKGROUND: Amino acid mutations in a large number of human proteins are known to be associated with heritable genetic disease. These disease-associated mutations (DAMs) are known to occur predominantly in positions essential to the structure and function of the proteins. Here, we examine how the relative perpetuation and conservation of amino acid positions modulate the genome-wide patterns of 8,627 human disease-associated mutations (DAMs) reported in 541 genes. We compare these patterns with 5,308 non-synonymous Single Nucleotide Polymorphisms (nSNPs) in 2,592 genes from primary SNP resources. RESULTS: The abundance of DAMs shows a negative relationship with the evolutionary rate of the amino acid positions harboring them. An opposite trend describes the distribution of nSNPs. DAMs are also preferentially found in the amino acid positions that are retained (or present) in multiple vertebrate species, whereas the nSNPs are over-abundant in the positions that have been lost (or absent) in the non-human vertebrates. These observations are consistent with the effect of purifying selection on natural variation, which also explains the existence of lower minor nSNP allele frequencies at highly-conserved amino acid positions. The biochemical severity of the inter-specific amino acid changes is also modulated by natural selection, with the fast-evolving positions containing more radical amino acid differences among species. Similarly, DAMs associated with early-onset diseases are more radical than those associated with the late-onset diseases. A small fraction of DAMs (10%) overlap with the amino acid differences between species within the same position, but are biochemically the most conservative group of amino acid differences in our datasets. Overlapping DAMs are found disproportionately in fast-evolving amino acid positions, which, along with the conservative nature of the amino acid changes, may have allowed some of them to escape natural selection until compensatory changes occur. CONCLUSION: The consistency and predictability of genome-wide patterns of disease- associated and neutral amino acid variants reported here underscores the importance of the consideration of evolutionary rates of amino acid positions in clinical and population genetic analyses aimed at understanding the nature and fate of disease-associated and neutral population variation. Establishing such general patterns is an early step in efforts to diagnose the pathogenic potentials of novel amino acid mutations.

Amino Acid Substitution↗
PubMed2006

TimeTree: a public knowledge-base of divergence times among organisms.

UNLABELLED: Biologists and other scientists routinely need to know times of divergence between species and to construct phylogenies calibrated to time (timetrees). Published studies reporting time estimates from molecular data have been increasing rapidly, but the data have been largely inaccessible to the greater community of scientists because of their complexity. TimeTree brings these data together in a consistent format and uses a hierarchical structure, corresponding to the tree of life, to maximize their utility. Results are presented and summarized, allowing users to quickly determine the range and robustness of time estimates and the degree of consensus from the published literature. AVAILABILITY: TimeTree is available at http://www.timetree.net

Biological Evolution↗
PubMed2006

Higher intensity of purifying selection on >90% of the human genes revealed by the intrinsic replacement mutation rates.

For over 3 decades, the rate of replacement mutations has been assumed to be equal to, and estimated from, the rate of "strictly" neutral sequence divergence in noncoding regions and in silent-codon positions where mutations do not alter the amino acid encoded. This assumption is fundamental to estimating the fraction of harmful protein mutations and to identifying adaptive evolution at individual codons and proteins. We show that the assumption is not justifiable because a much larger fraction of codon positions is involved in hypermutable CpG dinucleotides as compared with the introns, leading to a higher expected replacement mutation rate per site in a vast majority of the genes. Consideration of this difference reveals a higher intensity of purifying natural selection than previously inferred in human genes. We also show that a much smaller number of genes are expected to be evolving with positive selection than that predicted using sequence divergence at intron and silent positions in the human genome. These patterns indicate the need for using new approaches for estimating rates of amino acid-altering mutations in order to find positively selected genes and codons in genomes that contain hypermutable CpG's.

Animals↗
PubMed2006

Signatures of ecological resource availability in the animal and plant proteomes.

Although substantial and ecologically significant differences in elemental composition are well documented for whole organisms, little is known about whether such differences extend to lower levels of biological organization, such as the elemental composition of major molecules. In a proteome-scale investigation of 9 plant genomes and 9 animal genomes, we find that the nitrogen (N) content of plant proteins is lower than that in animal proteins. Furthermore, protein N content declines with the intensity of gene expression for plants, whereas the N content of animal proteins shows no consistent pattern with expression. Additional analyses indicate that the differences in N content between plant and animal proteomes and in plant proteins as a function of gene expression cannot be attributed to protein size, GC content, gene function, or amino acid properties. These patterns suggest that ecophysiological selection has operated to conserve N in plants via decreased reliance on N-rich amino acids. This inference was supported by an analysis of conserved and variable sites indicating that the N content of plant amino acids coded by variable sites is similar to that of the sites conserved between plant and animal genomes and shows no association with expression level. In contrast, in animals, the N content of amino acids coded by variable sites is significantly higher than that for conserved sites, suggesting relaxation of selective constraints for N usage in the animal lineage. This constitutes the first evidence for an influence of environmental resource availability on proteomes of multicellular organisms.

Amino Acids↗
PubMed2006

Impact of pediatric epilepsy on Indian families: influence of psychopathology and seizure related variables.

The impact of epilepsy on families has been little studied in the developing countries, where it is the most common neurological disorder among children. In Vellore, India, the impact on 132 families who had a child with epilepsy was rated with the Impact of Pediatric Epilepsy on the Family Scale (IPES). An adverse impact was experienced by 42% of families. Multivariate statistical analysis revealed four factors that were significantly associated with high impact: fewer years since diagnosis (OR=0.81, 95% CI=0.71-0.93), fewer months since last seizure (OR=0.58, 95% CI=0.39-0.87), treatment with multiple antiepileptic drugs (OR=4.34, 95% CI=1.22-15.52), and increased behavior problem scores on the Child Behavior Checklist (OR=1.10, 95% CI=1.05-1.14). Factor analysis of the IPES was also conducted as a comparison with earlier findings in a developed country. We suggest that early monotherapy should be employed whenever possible and that early recognition and treatment of associated psychological problems may help to reduce the burden on families.

Adaptation, Psychological↗
PubMed2006

Chromosomal localization, copy number assessment, and transcriptional status of BamHI repeat fractions in water buffalo Bubalus bubalis.

Higher eukaryotes contain a wide variety of repetitive DNA, although their functions often remain unknown. We describe cloning, chromosomal localization, copy number assessment, and transcriptional status of 1378- and 673-bp repeat fractions in the buffalo genome. The pDS5, representing the 1378-bp fragment, showed FISH signals in the centromeric region of acrocentric chromosomes only, whereas pDS4, corresponding to 673 bp, detected signals in the centromeric regions of all the chromosomes. Crosshybridization studies of pDS5 and pDS4 with genomic DNA from different sources showed signals only in buffalo, cattle, goat, and sheep. Real-time PCR analysis uncovered 1234 and 3420 copies of pDS5 and pDS4 fragments per the haploid genome, corresponding to 30 and 68 copies per chromosome, respectively. Analysis of cDNA from different tissues of buffalo with Real-time PCR showed maximum expression of pDS5 and pDS4 in the spleen and liver, respectively. Phylogenetic analysis of these sequences showed a close relationship between buffalo and cattle. The prospect of this approach in comparative genomics is highlighted.

Animals↗
PubMed2006

Transperitoneal, transmesocolic approach for laparoscopic excision of an extra-adrenal pheochromocytoma.

Laparoscopic surgery is an established treatment modality for adrenal disease, especially pheochromocytomas. We describe the successful excision of an extra-adrenal pheochromocytoma using a novel transperitoneal, transmesocolic approach. The tumor was located inferior to the left renal hilum in the para-aortic region and was found bulging through the descending mesocolon at laparoscopy. The tumor was removed without mobilization of the descending colon.

Humans↗
PubMed2006

Early recombinant factor VIIa therapy in acute intracerebral hemorrhage: promising approach.

Intracerebral hemorrhage (ICH) is the most devastating form of stroke with a high morbidity and mortality. ICH constitutes about 20-30% of all strokes, with the prevalence being higher in Asian population. Treatment of ICH is predominantly conservative, which includes control of blood pressure, use of anti-cerebral edema measures such as mannitol and mechanical ventilation. The benefit of early surgery in ICH is debatable. Initial hematoma volume and subsequent growth in its size are important predictors of a poor outcome in ICH. This means that therapies aimed at preventing hematoma enlargement in the earliest possible window period could lead to a better outcome in ICH. Recombinant factor VIIa (rFVIIa) is one such agent, which has been shown to prevent hematoma expansion and improve outcome in acute ICH. The purpose of the current review is to focus on the evidence regarding the usefulness of rFVIIa in acute ICH.

Cerebral Hemorrhage↗
PubMed2006

Cranial nerve involvement in patients with leprous neuropathy.

BACKGROUND: Leprosy is one of the most common causes of peripheral neuropathy, perhaps closely matched by diabetic neuropathy. Patterns of peripheral neuropathy in leprosy can be varied, which may include mononeuropathy, mononeuritis multiplex and symmetric polyneuropathy. Cranial nerves, especially facial and trigeminal nerves, are also commonly involved in leprosy. AIMS: To find out the pattern and spectrum of cranial nerve involvement in a consecutive series of patients with leprous neuropathy. SETTINGS AND DESIGN: A retrospective review of patients admitted with leprosy to the Neurology Department of a tertiary care center. MATERIALS AND METHODS: All consecutive patients admitted during an 8-year period (1995-2003) and diagnosed to have leprosy were included. They were clinically evaluated to determine the frequency and pattern of cranial nerve involvement. RESULTS: About 18% (9/51) of the leprosy patients seen during that period had clinical evidence of cranial nerve involvement. Facial and trigeminal nerves were the most commonly affected (five and four patients respectively). CONCLUSIONS: Cranial nerve involvement is common in leprosy, which emphasizes the need to carefully examine them. Also, one should exclude leprosy in patients presenting with isolated cranial neuropathies.

Adult↗
PubMed2006

Clozapine-responsive cluster headache.

Headaches are commonly associated with various psychiatric disorders. The comorbidity of migraine and psychiatric disorders has been well documented. Here we present a case of schizophrenia with comorbid headache treated with clozapine. The patient's headache fulfilled the diagnostic criteria for cluster headache (CH). To our knowledge this is the first report of CH responding to clozapine therapy. The relationship of headache and psychiatric disorders is a matter of debate and there has been very little research on the aspect of causality or direction of causation. The response of both the conditions to a serotonin-dopamine antagonist such as clozapine might be important in giving newer insights into the pathogenesis of these disorders. It also has the clinical implication of being useful in patients with dual diagnosis.

Adult↗
PubMed2006

Hypomania as an aura in migraine.

We report a 19-year-old man presenting to the department of Psychiatry for the evaluation of prominent behavioral symptoms associated with episodic headaches, with normal inter-episodic periods. A diagnosis of classic migraine with hypomanic aura was made. Other possible co-morbid or causative illnesses were excluded and preventive therapy with valproate was started due to the prominent affective symptoms as a part of the migranous aura. With this the frequency of headaches gradually decreased over the next four months. He was followed up for 2 years when he was found to be symptom-free. Recent research into the mechanisms of migraine has identified that the cortical hyperexcitability and an imbalance between neuronal inhibition and excitement mediated by gamma-aminobutyric acid and excitatory amino acids respectively may be the underlying mechanism. The high rate of affective disorders in patients with migraine, association of migraine with an aura comprising of mood symptoms and good response to treatment with mood-stabilisers might give newer insights into the pathophysiology of mood disorder as well.

Adult↗