Biology subjects

Henneberg, M.

Publications and source records attributed to Henneberg, M..

6 recordsLinked to original sources

bioRxiv2026

Relationship Between Gene Expression and Drug Response in Triple-Negative Breast Cancer: Leveraging Single-Cell RNA Sequencing and Machine Learning to Identify Biomarker Profiles

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by limited therapeutic options and poor prognosis. To address these challenges, we combined single-cell RNA sequencing (scRNA-seq) data with advanced machine learning techniques to find biomarkers that predict treatment response. Using tumor and blood samples from TNBC patients treated with either paclitaxel alone or in combination with atezolizumab, we constructed cellular maps, identified differentially expressed genes, and analyzed co-expression networks. Copy number variation (CNV) profiling and weighted gene co-expression network analysis (WGCNA) identified immune-related genes, including IL7R, CD6, and TNFAIP3, as candidate biomarkers linked to therapeutic response. A feature selection using Random Forest followed by bootstrap-enhanced K-nearest neighbors (K-NN) classification achieved high predictive accuracy across all subgroups (AUC > 0.93). Local Interpretable Model-Agnostic Explanations (LIME) based interpretability further identified important factors influencing treatment sensitivity and resistance, including EGR1, MKI67, C1QA/B/C, GZMB, and PRF1. Notably, blood-derived biomarkers showed strong predictive potential, highlighting the variability of liquid biopsy approaches for non-invasive monitoring. Our results indicate that integration of scRNA-seq with interpretable machine learning facilitates the identification of reliable biomarkers and yields clinically actionable insights for personalized therapeutic strategies in TNBC.

bioinformatics↗

bioRxiv2023

Microevolutionary Hypothesis of the Obesity Epidemic

The obesity epidemic represents potentially the largest phenotypic change in Homo sapiens since the origin of the species. Despite obesitys high heritability, a change in the gene pool has not generally been presumed as a potential cause of the obesity epidemic. Here we advance the hypothesis that a rapid change in the obesogenic gene pool has occurred second to the introduction of modern obstetrics dramatically altering evolutionary pressures on obesity - the microevolutionary hypothesis of the obesity epidemic. Obesity is known to increase childbirth related mortality several fold. Prior to modern obstetrics, childbirth related mortality occurred in over 10% of women. After modern obstetrics, this mortality reduced to a fraction of a percent, thereby lifting a strong negative selection pressure. Regression analysis of data for [~] 190 countries was carried out to examine associations between 1990 maternal death rates (MDR) and current obesity rates. Multivariate regression showed MDR correlated more strongly with national obesity rates than GDP, calorie intake and physical inactivity. Analyses controlling for confounders via partial correlation show that MDR explains approximately 11% of the variability of obesity rate between nations. For nations with MDR above the median (>0.45%), MDR explains over 20% of obesity variance, while calorie intake, and physical inactivity show no association with obesity in these nations. The microevolutionary hypothesis offers a parsimonious explanation of the global nature of the obesity epidemic. Significance StatementHumans underwent a rapid increase in obesity in the 20th century, and existing explanations for this trend are unsatisfactory. Here we present evidence that increases in obesity may be in large part attributable to microevolutionary changes brought about by dramatic reduction of childbirth mortality with the introduction of modern obstetrics. Given the higher relative risk of childbirth in women with obesity, obstetrics removed a strong negative selection pressure against obesity. This alteration would result in a rapid population-wide rise in obesity-promoting alleles. A cross-country analysis of earlier maternal death rates and obesity rate today found strong evidence supporting this hypothesis. These findings suggest recent medical intervention influenced the course of human evolution more profoundly than previously realized.

evolutionary biology↗

bioRxiv2021

Relationships between the hard and soft dimensions of the nose in Pan troglodytes and Homo sapiens reveal the nasal protrusions of Plio-Pleistocene hominids

By identifying similarity in bone and soft tissue covariation patterns in hominids, it is possible to produce facial approximation methods that are compatible with more than one species of primate. In this study, we conducted an interspecific comparison of the nasomaxillary region in chimpanzees and modern humans with the aim of producing a method for predicting the nasal protrusions of ancient Plio-Pleistocene hominids. We addressed this aim by first collecting and performing regression analyses of linear and angular measurements of nasal cavity length and inclination in modern humans (Homo sapiens; n = 72) and chimpanzees (Pan troglodytes; n = 19), and then by performing a set of out-of-group tests. The first test was performed on two subjects that belonged to the same genus as the training sample, i.e., Homo (n = 1) and Pan (n = 1), and the second test, which functioned as an interspecies compatibility test, was performed on Pan paniscus (n = 1), Gorilla gorilla (n = 3), Pongo pygmaeus (n = 1), Pongo abelli (n = 1), Symphalangus syndactylus (n = 3), and Papio hamadryas (n = 3). We identified statistically significant correlations in both humans and chimpanzees with slopes that displayed homogeneity of covariation. Joint prediction formulae were found to be compatible with humans and chimpanzees as well as all other African great apes, i.e., bonobos and gorillas. The main conclusion that can be drawn from this study is that regression models for approximating nasal projection are homogenous among humans and African apes and can thus be reasonably extended to ancestors leading to these clades.

paleontology↗

bioRxiv2021

Towards the restoration of ancient hominid craniofacial anatomy: Chimpanzee morphology reveals covariation between craniometrics and facial soft tissue thickness

In modern humans, facial soft tissue thicknesses have been shown to covary with craniometric dimensions. However, to date it has not been confirmed whether these relationships are shared with non-human apes. In this study, we analyze these relationships in chimpanzees (Pan troglodytes) with the aim of producing regression models for approximating facial soft tissue thicknesses in Plio-Pleistocene hominid individuals. Using CT scans of 19 subjects, 637 soft tissue, and 349 craniometric measurements, statistically significant multiple regression models were established for 26 points on the face and head. Examination of regression model validity resulted in minimal differences between observed and predicted soft tissue thickness values. Assessment of interspecies compatibility using a bonobo (Pan paniscus) and modern human (Homo sapiens) subject resulted in minimal differences for the bonobo but large differences for the modern human. These results clearly show that (1) soft tissue thicknesses covary with craniometric dimensions in P. troglodytes, (2) confirms that such covariation is uniformly present in both extant Homo and Pan species, and (3) suggests that chimp-derived regression models have interspecies compatibility with hominids who have similar craniometric dimensions to P. troglodytes. As the craniometric dimensions of early hominids, such as South African australopithecines, are more similar to P. troglodytes than those of H. sapiens, chimpanzee-derived regression models may be used for approximating their craniofacial anatomy. It is hoped that the results of the present study and the reference dataset for facial soft tissue thicknesses of chimpanzees it provides will encourage further research into this topic.

zoology↗

bioRxiv2020

Human major infections: tuberculosis, treponematoses, leprosy - a paleopathological perspective of their evolution

ObjectiveThe key to evolution is reproduction. Pathogens can either kill the human host or can invade the host without causing death, thus ensuring their own survival, reproduction and spread. Tuberculosis, treponematoses and leprosy are widespread chronic infectious diseases whereby the host is not immediately killed. These diseases are examples of the co-evolution of host and pathogen. They can be well studied as the paleopathological record is extensive, spanning over 200 human generations. MethodsThe paleopathology of each disease has been well documented in the form of published synthetic analyses recording each known case and case frequencies in the samples they were derived from. Here the data from these synthetic analyses were re-analysed to show changes in the prevalence of each disease over time. A total of 69,379 skeletons are included in this study. ResultsThere was ultimately a decline in the prevalence of each disease over time, this decline was statistically significant (Chi-squared, p<0.001). A trend may start with the increase in the diseases prevalence before the prevalence declines, in tuberculosis the decline is monotonic. ConclusionsIncrease in skeletal changes resulting from the respective diseases appears in the initial period of host-disease contact, followed by a decline resulting from co-adaptation that is mutually beneficial for the disease (spread and maintenance of pathogen) and host (less pathological reactions to the infection). Eventually either the host may become immune or tolerant, or the pathogen tends to be commensalic rather than parasitic.

evolutionary biology↗

bioRxiv2019

Non-canonical localization of RubisCO under high light conditions in the toxic cyanobacterium Microcystis aeruginosa PCC7806

The frequent production of the hepatotoxin microcystin and its impact on the life-style of bloom-forming cyanobacteria are poorly understood. Here we report that microcystin interferes with the assembly and the subcellular localization of RubisCO, in Microcystis aeruginosa PCC7806. Immunofluorescence, electron microscopic and cellular fractionation studies revealed a pronounced heterogeneity in the subcellular localization of RubisCO. At high cell density, RubisCO particles are largely separate from carboxysomes in M. aeruginosa and relocate to the cytoplasmic membrane under high-light conditions. We hypothesize that the binding of microcystin to RubisCO promotes its membrane association and enables an extreme versatility of the enzyme. Steady-state levels of the RubisCO CO2 fixation product 3-phosphoglycerate are significantly higher in the microcystin-producing wild type. We also detected noticeable amounts of the RubisCO oxygenase reaction product secreted into the medium that may support the mutual interaction of M. aeruginosa with its heterotrophic microbial community.

microbiology↗