Comprehensive analyses of m6A regulators and interactive coding and non-coding RNAs across 32 cancer types

N6-Methyladenosine (m6A) is an RNA modification that interacts with numerous coding and non-coding RNAs and plays important roles in the development of cancers. Nonetheless, the clinical impacts of m6A interactive genes on these cancers largely remain unclear since most studies focus only on a single cancer type. We comprehensively evaluated m6A modification patterns, including 23 m6A regulators and 83 interactive coding and non-coding RNAs among 9,804 pan-cancer samples. We used clustering analysis to identify m6A subtypes and constructed the m6A signature based on an unsupervised approach. We used the signatures to identify potential m6A modification targets across the genome. The prognostic value of one target was further validated in 3,444 samples from six external datasets. We developed three distinct m6A modification subtypes with different tumor microenvironment cell infiltration degrees: immunological, intermediate, and tumor proliferative. They were significantly associated with overall survival in 24 of 27 cancer types. Our constructed individual-level m6A signature was associated with survival, tumor mutation burden, and classical pathways. With the signature, we identified 114 novel genes as potential m6A targets. The gene shared most commonly between cancer types, BCL9L, is an oncogene and interacts with m6A patterns in the Wnt signaling pathway. In conclusion, m6A regulators and their interactive genes impact the outcome of various cancers. Evaluating the m6A subtype and the signature of individual tumors may inform the design of adjuvant treatments.

Representation of Color, Form, and their Conjunction across the Human Ventral Visual Pathway

Despite decades of neuroscience research, our understanding of the relationship between color and form processing in the primate ventral visual pathway remains incomplete. Using fMRI multivoxel pattern analysis, this study examined the coding of color with both a simple form feature (orientation) and a mid-level form feature (curvature) in human early visual areas V1 to V4, posterior and central color regions, and shape areas in ventral and lateral occipito-temporal cortex. With the exception of the central color region (which showed color but not form decoding), successful color and form decoding was found in all other regions examined, even for color and shape regions showing univariate sensitivity to one feature. That said, all regions exhibited significant feature decoding biases, with decoding from color and shape regions largely consistent with their univariate preferences. Color and form are thus represented in neither a completely distributed nor a completely modular manner, but a biased distributed manner. Interestingly, coding of one feature in a brain region was always tolerant to changes in the other feature, indicating relative independence of color and form coding throughout the ventral visual cortex. Although evidence for interactive coding of color and form also existed, the effect was weak and only existed for color and orientation conjunctions in early visual cortex. No evidence for interactive coding of color and curvature was found. The predominant relationship between color and form coding in the human brain appears to be one of anatomical coexistence (in a biased distributed manner), but representational independence.