Toward Robots with Peripersonal Space Representation for Adaptive Behaviors

The abilities to adapt and act autonomously in an unstructured and human-oriented environment are necessarily vital for the next generation of robots, which aim to safely cooperate with humans. While this adaptability is natural and feasible for humans, it is still very complex and challenging for robots. Observations and findings from psychology and neuroscience in respect to the development of the human sensorimotor system can inform the development of novel approaches to adaptive robotics. Among these is the formation of the representation of space closely surrounding the body, the Peripersonal Space (PPS) , from multisensory sources like vision, hearing, touch and proprioception, which helps to facilitate human activities within their surroundings. Taking inspiration from the virtual safety margin formed by the PPS representation in humans, this thesis first constructs an equivalent model of the safety zone for each body part of the iCub humanoid robot. This PPS layer serves as a distributed collision predictor, which translates visually detected objects approaching a robot\u2019s body parts (e.g., arm, hand) into the probabilities of a collision between those objects and body parts. This leads to adaptive avoidance behaviors in the robot via an optimization-based reactive controller. Notably, this visual reactive control pipeline can also seamlessly incorporate tactile input to guarantee safety in both pre- and post-collision phases in physical Human-Robot Interaction (pHRI). Concurrently, the controller is also able to take into account multiple targets (of manipulation reaching tasks) generated by a multiple Cartesian point planner. All components, namely the PPS, the multi-target motion planner (for manipulation reaching tasks), the reaching-with-avoidance controller and the humancentred visual perception, are combined harmoniously to form a hybrid control framework designed to provide safety for robots\u2019 interactions in a cluttered environment shared with human partners. Later, motivated by the development of manipulation skills in infants, in which the multisensory integration is thought to play an important role, a learning framework is proposed to allow a robot to learn the processes of forming sensory representations, namely visuomotor and visuotactile, from their own motor activities in the environment. Both multisensory integration models are constructed with Deep Neural Networks (DNNs) in such a way that their outputs are represented in motor space to facilitate the robot\u2019s subsequent actions

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation

Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility