Biology subjects

Hochheiser, H.

Publications and source records attributed to Hochheiser, H..

4 recordsLinked to original sources

bioRxiv2023

Representation and Retrieval of Brain Connectivity Information derived from TMS Experiments

BackgroundTranscranial magnetic stimulation (TMS) is a painless non-invasive method that allows focal activation or deactivation of a human brain region in order to assess effects on other brain regions. As such, it has a unique role in elucidating brain connectivity during behavior and at rest. Information regarding brain connectivity derived from TMS experiments has been published in hundreds of papers but is not accessible in aggregate. ObjectiveOur objective was to identify, extract, and represent TMS-connectivity data in a graph database. This approach uses nodes connected by edges to capture the directed nature of interregional communication in the brain while also being flexible enough to contain other information about the connections, such as the source of information and details about the experiments that produced them. MethodsData related to interregional brain connectivity is first extracted from full-text publications, with creation of a table-like structure that list data of multiple types, principally the source and target brain regions, sign (excitatory/inhibitory) and latency. While machine-reading methods were explored, so far human experts have had to extract and verify data. These data are used to populate a neo4j graph database. A graphical user interface coupled with a query system allows users to search for networks and display information about connections between any two brain regions of interest. ResultsExperiments involving two TMS stimulating coils, in which one is over a putative source region and the other is over another region with a measurable effect in the body (such as the primary motor cortex) are the most straightforward to represent in the database. Even in those experiments, differing conventions for naming regions, and differing experimental parameters such as stimulation intensity and coil position, create issues for representing data from multiple studies in the same database. Other types of experiments, such a neuromodulatory stimulation such as rTMS, can provide information regarding connectivity, but are harder to represent. But we have, thus far, stored information about 100 connections in the database and demonstrated its utility in exploring direct and indirect connections between brain regions. We have also explored adding a causal inference method to those connections, allowing information about latency to shape the connections retrieved given latency limits. ConclusionA graph database can flexibly store information about interregional brain connectivity and is particularly useful for exploring the temporal aspects of brain networks.

neuroscience↗

bioRxiv2018

Longitudinal Visual Analytics for Unpacking the Cancer Journey

Retrospective cancer research requires identification of patients matching both categorical and temporal inclusion criteria, often based on factors exclusively available in clinical notes. Although natural language processing approaches for inferring higher-level concepts have shown promise for bringing structure to clinical texts, interpreting results is often challenging, involving the need to move between abstracted representations and constituent text elements. We discuss qualitative inquiry into user tasks and goals, data elements and models resulting in an innovative natural language processing pipeline and a visual analytics tool designed to facilitate interpretation of patient summaries and identification of cohorts for retrospective research.

cancer biology↗

bioRxiv2018

Systematic Discovery of the Functional Impact of Somatic Genome Alterations in Individual Tumors through Tumor-specific Causal Inference

We report a tumor-specific causal inference (TCI) framework, which discovers causative somatic genome alterations (SGAs) through inferring causal relationships between SGAs and molecular phenotypes (e.g., transcriptomic, proteomic, or metabolomic changes) within an individual tumor. We applied the TCI algorithm to tumors from The Cancer Genome Atlas (TCGA) and identified those SGAs that causally regulate the differentially expressed genes (DEGs) within each tumor. Overall, TCI identified 634 SGAs that cause cancer-related DEGs in a significant number of tumors, including most of the previously known drivers and many novel candidate cancer drivers. The inferred causal relationships are statistically robust and biologically sensible, and multiple lines of experimental evidence support the predicted functional impact of both well-known and novel candidate drivers. By identifying major candidate drivers and revealing their functional impact in a tumor, TCI shed light on disease mechanisms of each tumor, providing useful information for advancing cancer biology and precision oncology.\n\nSignificance statementsCancer is mainly caused by SGAs. Precision oncology involves identifying and targeting tumor-specific aberrations resulting from causative SGAs. TCI is a novel computational framework for discovering the causative SGAs and their impact on oncogenic processes, thus revealing tumor-specific disease mechanisms. This information can be used to guide precision oncology.

cancer biology↗

bioRxiv2016

The Monarch Initiative: Insights across species reveal human disease mechanisms

The principles of genetics apply across the whole tree of life: on a cellular level, we share mechanisms with species from which we diverged millions or even billions of years ago. We can exploit this common ancestry at the level of sequences, but also in terms of observable outcomes (phenotypes), to learn more about health and disease for humans and all other species. Applying the range of available knowledge to solve challenging disease problems requires unified data relating genomics, phenotypes, and disease; it also requires computational tools that leverage these multimodal data to inform interpretations by geneticists and to suggest experiments. However, the distribution and heterogeneity of databases is a major impediment: databases tend to focus either on a single data type across species, or on single species across data types. Although each database provides rich, high-quality information, no single one provides unified data that is comprehensive across species, biological scales, and data types. Without a big-picture view of the data, many questions in genetics are difficult or impossible to answer. The Monarch Initiative (https://monarchinitiative.org) is an international consortium dedicated to providing computational tools that leverage a computational representation of phenotypic data for genotype-phenotype analysis, genomic diagnostics, and precision medicine on the basis of a large-scale platform of multimodal data that is deeply integrated across species and covering broad areas of disease.

evolutionary biology↗