arXiv subjects

Vince Grolmusz

Publications and source records attributed to Vince Grolmusz.

At least 37 records · Page 2Linked to original sources

arXiv2019

The Frequent Complete Subgraphs in the Human Connectome

While it is still not possible to describe the neural-level connections of the human brain, we can map the human connectome with several hundred vertices, by the application of diffusion-MRI based techniques. In these graphs, the nodes correspond to anatomically identified gray matter areas of the brain, while the edges correspond to the axonal fibers, connecting these areas. In our previous contributions, we have described numerous graph-theoretical phenomena of the human connectomes. Here we map the frequent complete subgraphs of the human brain networks: in these subgraphs, every pair of vertices is connected by an edge. We also examine sex differences in the results. The mapping of the frequent subgraphs gives robust substructures in the graph: if a subgraph is present in the 80% of the graphs, then, most probably, it could not be an artifact of the measurement or the data processing workflow. We list here the frequent complete subgraphs of the human braingraphs of 414 subjects, each with 463 nodes, with a frequency threshold of 80%, and identify 812 complete subgraphs, which are more frequent in male and 224 complete subgraphs, which are more frequent in female connectomes.

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arXiv2018

The Frequent Network Neighborhood Mapping of the Human Hippocampus Shows Much More Frequent Neighbor Sets in Males Than in Females

In the study of the human connectome, the vertices and the edges of the network of the human brain are analyzed: the vertices of the graphs are the anatomically identified gray matter areas of the subjects; this set is exactly the same for all the subjects. The edges of the graphs correspond to the axonal fibers, connecting these areas. In the biological applications of graph theory, it happens very rarely that scientists examine numerous large graphs on the very same, labeled vertex set. Exactly this is the case in the study of the connectomes. Because of the particularity of these sets of graphs, novel, robust methods need to be developed for their analysis. Here we introduce the new method of the Frequent Network Neighborhood Mapping for the connectome, which serves as a robust identification of the neighborhoods of given vertices of special interest in the graph. We apply the novel method for mapping the neighborhoods of the human hippocampus and discover strong statistical asymmetries between the connectomes of the sexes, computed from the Human Connectome Project. We analyze 413 braingraphs, each with 463 nodes. We show that the hippocampi of men have much more significantly frequent neighbor sets than women; therefore, in a sense, the connections of the hippocampi are more regularly distributed in men and more varied in women. Our results are in contrast to the volumetric studies of the human hippocampus, where it was shown that the relative volume of the hippocampus is the same in men and women.

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arXiv2018

PDB_Amyloid: The Extended Live Amyloid Structure List from the PDB

The Protein Data Bank (PDB) contains more than 135 000 entries today. From these, relatively few amyloid structures can be identified, since amyloids are insoluble in water. Therefore, mostly solid state NMR-recorded amyloid structures are deposited in the PDB. Based on the geometric analysis of these deposited structures we have prepared an automatically updated webserver, which generates the list of the deposited amyloid structures, and, additionally, those globular protein entries, which have amyloid-like substructures of a given size and characteristics. We have found that applying only the properly chosen geometric conditions, it is possible to identify the deposited amyloid structures, and a number of globular proteins with amyloid-like substructures. We have analyzed these globular proteins and have found that many of them are known to form amyloids more easily than many other globular proteins. Our results relate to the method of (Stankovic, I. et al. (2017): Construction of Amyloid PDB Files Database. Transactions on Internet Research. 13 (1): 47-51), who have applied a hybrid textual-search and geometric approach for finding amyloids in the PDB. If one intends to identify a subset of the PDB for some applications, the identification algorithm needs to be re-run periodically, since in 2017, on average, every day 30 new entries were deposited in the data bank. Our webserver is updated regularly and automatically, and the identified amyloid- and partial amyloid structures can be viewed or their list can be downloaded from the site https://pitgroup.org/amyloid.

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arXiv2017

The Frequent Subgraphs of the Connectome of the Human Brain

In mapping the human structural connectome, we are in a very fortunate situation: one can compute and compare graphs, describing the cerebral connections between the very same, anatomically identified small regions of the gray matter among hundreds of human subjects. The comparison of these graphs has led to numerous recent results, as the (i) discovery that women's connectomes have deeper and richer connectivity-related graph parameters like those of men, or (ii) the description of more and less conservatively connected lobes and cerebral regions, and (iii) the discovery of the phenomenon of the Consensus Connectome Dynamics. Today one of the greatest challenges of brain science is the description and modeling of the circuitry of the human brain. For this goal, we need to identify sub-circuits that are present in almost all human subjects and those, which are much less frequent: the former sub-circuits most probably have functions with general importance, the latter sub-circuits are probably related to the individual variability of the brain structure and functions. The present contribution describes the frequent connected subgraphs (instead of sub-circuits) of at most 6 edges in the human brain. We analyze these frequent graphs and also examine sex differences in these graphs: we demonstrate numerous connected sub-graphs that are more frequent in female or the male connectome. While our results describe subgraphs, instead of sub-circuits, we need to note that all macroscopic sub-circuits correspond to an underlying connected subgraph. Our data source is the public release of the Human Connectome Project, and we are applying the data of 426 human subjects in this study.

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arXiv2017

MetaHMM: A Webserver for Identifying Novel Genes with Specified Functions in Metagenomic Samples

The fast and affordable sequencing of large clinical and environmental metagenomic datasets opens up new horizons in medical and biotechnological applications. It is believed that today we have described only about 1\% of the microorganisms on the Earth, therefore, metagenomic analysis mostly deals with unknown species in the samples. Microbial communities in extreme environments may contain genes with high biotechnological potential, and clinical metagenomes, related to diseases, may uncover still unknown pathogens and pathological mechanisms in known diseases. While the species-level identification and description of the taxa in the samples does not seem to be possible today, we can search for novel genes with known functions in these samples, using numerous techniques, including artificial intelligence tools, like the hidden Markov models (HMMs). Here we describe a simple-to-use webserver, the MetaHMM, which is capable of homology-based automatic model-building for the genes to be searched for, and it also finds the closest matches in the metagenome. The webserver uses already highly successful building blocks: it performs multiple alignment by applying Clustal Omega, builds a hidden Markov model with HMMER components of hmmbuild and uses hmmsearch for finding similar sequences to the specified model in the metagenomes. The webserver is publicly available at \url{https://metahmm.pitgroup.org}.

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arXiv2017

SCARF: A Biomedical Association Rule Finding Webserver

The analysis of enormous datasets with missing data entries is a standard task in biological and medical data processing. Large-scale, multi-institution clinical studies are the typical examples of such datasets. These sets make possible the search for multi-parametric relations since from the plenty of the data one is likely to find a satisfying number of subjects with the required parameter ensembles. Specifically, finding combinatorial biomarkers for some given condition also needs a very large dataset to analyze. For this goal, statistical regression analysis is not the preferred tool of choice, since (i) the {\em a priori} knowledge of the parameter-sets to analyze is missing, and (ii) typically relatively few subjects have the interesting parameter-value ensembles for the analysis. For fast and automatic multi-parametric relation discovery association-rule finding tools are used for more than two decades in the data-mining community. Here we present the SCARF webserver for {\em generalized} association rule mining. Association rules are of the form: $a$ AND $b$ AND ... AND $x \rightarrow y$, meaning that the presence of properties $a$ AND $b$ AND ... AND $x$ implies property $y$; our algorithm finds generalized association rules, since it also finds logical disjunctions (i.e., ORs) at the left-hand side, allowing the discovery of more complex rules in a more compressed form in the database. This feature also helps reducing the typically very large result-tables of such studies, since allowing ORs in the left-hand side of a single rule could include dozens of classical rules. The capabilities of the SCARF algorithm were demonstrated in mining the Alzheimer's database of the Coalition Against Major Diseases (CAMD) in our recent publication (Archives of Gerontology and Geriatrics Vol. 73, pp. 300-307, 2017). Here we describe the webserver implementation of the algorithm.

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arXiv2017

Comparing Advanced Graph-Theoretical Parameters of the Connectomes of the Lobes of the Human Brain

Deep, classical graph-theoretical parameters, like the size of the minimum vertex cover, the chromatic number, or the eigengap of the adjacency matrix of the graph were studied widely by mathematicians in the last century. Most researchers today study much simpler parameters of braingraphs or connectomes which were defined in the last twenty years for enormous networks -- like the graph of the World Wide Web -- with hundreds of millions of nodes. Since the connectomes, describing the connections of the human brain, typically contain several hundred vertices today, one can compute and analyze the much deeper, harder-to-compute classical graph parameters for these, relatively small graphs of the brain. This deeper approach has proven to be very successful in the comparison of the connectomes of the sexes in our earlier works: we have shown that graph parameters, deeply characterizing the graph connectivity are significantly better in women's connectomes than in men's. In the present contribution we compare numerous graph parameters in the three largest lobes --- frontal, parietal, temporal --- and in both hemispheres of the brain. We apply the diffusion weighted imaging data of 423 subjects of the NIH-funded Human Connectome Project, and present some findings, never described before, including that the right parietal lobe contains significantly more edges, has higher average degree, density, larger minimum vertex cover and Hoffman bound than the left parietal lobe. Similar advantages in the deep graph connectivity properties are hold for the left frontal vs. the right frontal and for the right temporal vs. the left temporal lobes.

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arXiv2017

SECLAF: A Webserver and Deep Neural Network Design Tool for Biological Sequence Classification

Artificial intelligence (AI) tools are gaining more and more ground each year in bioinformatics. Learning algorithms can be taught easily by using the existing enormous biological databases, and the resulting models can be used for the high-quality classification of novel, un-categorized data in numerous areas, including biological sequence analysis. Here we introduce SECLAF, an artificial neural-net based biological sequence classifier framework, which uses the Tensorflow library of Google, Inc. By applying SECLAF for residue-sequences, we have reported (Methods (2017), https://doi.org/10.1016/j.ymeth.2017.06.034) the most accurate multi-label protein classifier to date (UniProt --into 698 classes-- AUC 99.99\%; Gene Ontology --into 983 classes-- AUC 99.45\%). Our framework SECLAF can be applied for other sequence classification tasks, as we describe in the present contribution. Availability and implementation: The program SECLAF is implemented in Python, and is available for download, with example datasets at the website https://pitgroup.org/seclaf/. For Gene Ontology and UniProt based classifications a webserver is also available at the address above.

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arXiv2017

Near Perfect Protein Multi-Label Classification with Deep Neural Networks

Artificial neural networks (ANNs) have gained a well-deserved popularity among machine learning tools upon their recent successful applications in image- and sound processing and classification problems. ANNs have also been applied for predicting the family or function of a protein, knowing its residue sequence. Here we present two new ANNs with multi-label classification ability, showing impressive accuracy when classifying protein sequences into 698 UniProt families (AUC=99.99%) and 983 Gene Ontology classes (AUC=99.45%).

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arXiv2016

The Robustness and the Doubly-Preferential Attachment Simulation of the Consensus Connectome Dynamics of the Human Brain

The increasing quantity and quality of the publicly available human cerebral diffusion MRI data make possible the study of the brain as it was unimaginable before. The Consensus Connectome Dynamics (CCD) is a remarkable phenomenon that was discovered by continuously decreasing the minimum confidence-parameter at the graphical interface of the Budapest Reference Connectome Server (\url{http://connectome.pitgroup.org}). The Budapest Reference Connectome Server depicts the cerebral connections of $n=418$ subjects with a frequency-parameter $k$: For any $k=1,2,...,n$ one can view the graph of the edges that are present in at least $k$ connectomes. If parameter $k$ is decreased one-by-one from $k=n$ through $k=1$ then more and more edges appear in the graph, since the inclusion condition is relaxed. The surprising observation is that the appearance of the edges is far from random: it resembles a growing, complex structure, like a tree or a shrub (visualized on \url{https://www.youtube.com/watch?v=yxlyudPaVUE}). Here we examine the robustness of the CCD phenomenon, and we show that it is almost independent of the particular choice of the set of underlying individual connectomes, yielding the CCD phenomenon. This result shows that the CCD phenomenon is very likely a biological property of the human brain and not just a property of the data sets examined. We also present a simulation that well-describes the growth of the CCD structure: in our random graph model a doubly-preferential attachment distribution is found to mimic the CCD: a new edge appear with a probability proportional to the sum of the degrees of the endpoints of the new edge.

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arXiv2016

The braingraph.org Database of High Resolution Structural Connectomes and the Brain Graph Tools

Based on the data of the NIH-funded Human Connectome Project, we have computed structural connectomes of 426 human subjects in five different resolutions of 83, 129, 234, 463 and 1015 nodes and several edge weights. The graphs are given in anatomically annotated GraphML format that facilitates better further processing and visualization. For 96 subjects, the anatomically classified sub-graphs can also be accessed, formed from the vertices corresponding to distinct lobes or even smaller regions of interests of the brain. For example, one can easily download and study the connectomes, restricted to the frontal lobes or just to the left precuneus of 96 subjects using the data. Partially directed connectomes of 423 subjects are also available for download. We also present a GitHub-deposited set of tools, called the Brain Graph Tools, for several processing tasks of the connectomes on the site \url{http://braingraph.org}.

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arXiv2016

High-Resolution Directed Human Connectomes and the Consensus Connectome Dynamics

Here we show a method of directing the edges of the connectomes, prepared from diffusion tensor imaging (DTI) datasets from the human brain. Before the present work, no high-definition directed braingraphs (or connectomes) were published, because the tractography methods in use are not capable of assigning directions to the neural tracts discovered. Previous work on the functional connectomes applied low-resolution functional MRI-detected statistical causality for the assignment of directions of connectomes of typically several dozens of vertices. Our method is based on the phenomenon of the "Consensus Connectome Dynamics" (CCD), described earlier by our research group. In this contribution, we apply the method to the 423 braingraphs, each with 1015 vertices, computed from the public release of the Human Connectome Project, and we also made the directed connectomes publicly available at the site \url{http://braingraph.org}. We also show the robustness of our edge directing method in four independently chosen connectome datasets: we have found that 86\% of the edges, which were present in all four datasets, get the very same directions in all datasets; therefore the direction method is robust, it does not depend on the particular choice of the dataset. We think that our present contribution opens up new possibilities in the analysis of the high-definition human connectome: from now on we can work with a robust assignment of directions of the connections of the human brain.

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arXiv2016

The Dorsal Striatum and the Dynamics of the Consensus Connectomes in the Frontal Lobe of the Human Brain

In the applications of the graph theory it is unusual that one considers numerous, pairwise different graphs on the very same set of vertices. In the case of human braingraphs or connectomes, however, this is the standard situation: the nodes correspond to anatomically identified cerebral regions, and two vertices are connected by an edge if a diffusion MRI-based workflow identifies a fiber of axons, running between the two regions, corresponding to the two vertices. Therefore, if we examine the braingraphs of $n$ subjects, then we have $n$ graphs on the very same, anatomically identified vertex set. It is a natural idea to describe the $k$-frequently appearing edges in these graphs: the edges that are present between the same two vertices in at least $k$ out of the $n$ graphs. Based on the NIH-funded large Human Connectome Project's public data release, we have reported the construction of the Budapest Reference Connectome Server \url{http://connectome.pitgroup.org} that generates and visualizes these $k$-frequently appearing edges. We call the graphs of the $k$-frequently appearing edges "$k$-consensus connectomes" since an edge could be included only if it is present in at least $k$ graphs out of $n$. Considering the whole human brain, we have reported a surprising property of these consensus connectomes earlier. In the present work we are focusing on the frontal lobe of the brain, and we report here a similarly surprising dynamical property of the consensus connectomes when $k$ is gradually changed from $k=n$ to $k=1$: the connections between the nodes of the frontal lobe are seemingly emanating from those nodes that were connected to sub-cortical structures of the dorsal striatum: the caudate nucleus, and the putamen. We hypothesize that this dynamic behavior copies the axonal fiber development of the frontal lobe.

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arXiv2016

Human Sexual Dimorphism of the Relative Cerebral Area Volumes in the Data of the Human Connectome Project

The average human brain volume of the males is larger than that of the females. Several MRI voxel-based morphometry studies show that the gray matter/white matter ratio is larger in females. Here we have analyzed the recent public release of the Human Connectome Project, and by using the diffusion MRI data of 511 subjects (209 men and 302 women), we have found that the relative volumes of numerous subcortical areas and the gray matter of most cortical areas are significantly larger in women than in men. Additionally, we have discovered differences of the strengths of the sexual correlations between the same structures in different hemispheres.

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arXiv2016

How to Direct the Edges of the Connectomes: Dynamics of the Consensus Connectomes and the Development of the Connections in the Human Brain

The human connectome is the object of an intensive research today. In these graphs, the vertices correspond to the small areas of the gray matter, and two vertices are connected by an edge, if a diffusion-MRI based workflow finds connections between those areas. One main question of the field is discovering the directions of the edges. In a previous work we have reported the construction of the Budapest Reference Connectome Server http://connectome.pitgroup.org from the data recorded in the Human Connectome Project of the NIH. After the server had been published, we recognized a surprising and unforeseen property of it: The server can generate the braingraph of connections that are present in at least $k$ graphs out of the 418, for any value of $k=1,2,...,418$. When the value of $k$ is changed from $k=418$ through 1 by moving a slider at the webserver from right to left, more and more edges appear in the consensus graph. The astonishing observation is that the appearance of the new edges is not random: it is similar to a growing tree. We hypothesize that this movement of the slider in the webserver may copy the development of the connections in the human brain in the following sense: the connections that are present in all subjects are the oldest ones, and those that are present in a decreasing fraction of subjects are gradually the newer connections in the individual brain development. An animation on the phenomenon is available at https://youtu.be/EnWwIf_HNjw. Based on this hypothesis, we can assign directions to the edges of the connectome as follows: Let $G_i$ denote the consensus connectome where each edge is present in at least $i$ graphs. Suppose that vertex $v$ is isolated in $G_{k+1}$, and becomes connected to a vertex $u$ in $G_k$, where $u$ was connected to other vertices already in $G_{k+1}$. Then we direct this $(v,u)$ edge from $v$ to $u$.

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arXiv2016

Parameterizable Consensus Connectomes from the Human Connectome Project: The Budapest Reference Connectome Server v3.0

Connections of the living human brain, on a macroscopic scale, can be mapped by a diffusion MR imaging based workflow. Since the same anatomic regions can be corresponded between distinct brains, one can compare the presence or the absence of the edges, connecting the very same two anatomic regions, among multiple cortices. Previously, we have constructed the consensus braingraphs on 1015 vertices first in five, then in 96 subjects in the Budapest Reference Connectome Server v1.0 and v2.0, respectively. Here we report the construction of the version 3.0 of the server, generating the common edges of the connectomes of variously parameterizable subsets of the 1015-vertex connectomes of 477 subjects of the Human Connectome Project's 500-subject release. The consensus connectomes are downloadable in csv and GraphML formats, and they are also visualized on the server's page. The consensus connectomes of the server can be considered as the "average, healthy" human connectome since all of their connections are present in at least $k$ subjects, where the default value of $k=209$, but it can also be modified freely at the web server. The webserver is available at \url{http://connectome.pitgroup.org}.

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arXiv2016

Mapping Correlations of Psychological and Connectomical Properties of the Dataset of the Human Connectome Project with the Maximum Spanning Tree Method

We analyzed correlations between more than 700 psychological-, anatomical- and connectome--properties, originated from the Human Connectome Project's (HCP) 500-subject dataset. Apart from numerous natural correlations, which describe parameters computable or approximable from one another, we have discovered numerous significant correlations in the dataset, never described before. We also have found correlations described very recently independently from the HCP-dataset: e.g., between gambling behavior and the number of the connections leaving the insula.

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arXiv2015

The Advantage is at the Ladies: Brain Size Bias-Compensated Graph-Theoretical Parameters are Also Better in Women's Connectomes

In our previous study we have shown that the female connectomes have significantly better, deep graph-theoretical parameters, related to superior "connectivity", than the connectome of the males. Since the average female brain is smaller than the average male brain, one cannot rule out that the significant advantages are due to the size- and not to the sex-differences in the data. To filter out the possible brain-volume related artifacts, we have chosen 36 small male and 36 large female brains such that all the brains in the female set are larger than all the brains in the male set. For the sets, we have computed the corresponding braingraphs and computed numerous graph-theoretical parameters. We have found that (i) the small male brains lack the better connectivity advantages shown in our previous study for female brains in general; (ii) in numerous parameters, the connectomes computed from the large-brain females, still have the significant, deep connectivity advantages, demonstrated in our previous study.

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