{"bundle_type":"pith_open_graph_bundle","bundle_version":"1.0","pith_number":"pith:2015:CZINMWP5ORAO6EW3TIH5J5QJOT","short_pith_number":"pith:CZINMWP5","canonical_record":{"source":{"id":"1510.04612","kind":"arxiv","version":1},"metadata":{"license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","primary_cat":"q-bio.BM","submitted_at":"2015-10-15T16:34:12Z","cross_cats_sorted":[],"title_canon_sha256":"cfda17aa79497d58ea57ab99367d49cb7d338e57258407350cb244d5c166a520","abstract_canon_sha256":"f870f5cd1c04c1d5c8914a20aa8600cc4b80bd8d51eb765d7465881e694c7563"},"schema_version":"1.0"},"canonical_sha256":"1650d659fd7440ef12db9a0fd4f60974d698bf38be4ac02b45ca5e5818c67c8e","source":{"kind":"arxiv","id":"1510.04612","version":1},"source_aliases":[{"alias_kind":"arxiv","alias_value":"1510.04612","created_at":"2026-05-18T00:52:44Z"},{"alias_kind":"arxiv_version","alias_value":"1510.04612v1","created_at":"2026-05-18T00:52:44Z"},{"alias_kind":"doi","alias_value":"10.48550/arxiv.1510.04612","created_at":"2026-05-18T00:52:44Z"},{"alias_kind":"pith_short_12","alias_value":"CZINMWP5ORAO","created_at":"2026-05-18T12:29:17Z"},{"alias_kind":"pith_short_16","alias_value":"CZINMWP5ORAO6EW3","created_at":"2026-05-18T12:29:17Z"},{"alias_kind":"pith_short_8","alias_value":"CZINMWP5","created_at":"2026-05-18T12:29:17Z"}],"events":[{"event_type":"record_created","subject_pith_number":"pith:2015:CZINMWP5ORAO6EW3TIH5J5QJOT","target":"record","payload":{"canonical_record":{"source":{"id":"1510.04612","kind":"arxiv","version":1},"metadata":{"license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","primary_cat":"q-bio.BM","submitted_at":"2015-10-15T16:34:12Z","cross_cats_sorted":[],"title_canon_sha256":"cfda17aa79497d58ea57ab99367d49cb7d338e57258407350cb244d5c166a520","abstract_canon_sha256":"f870f5cd1c04c1d5c8914a20aa8600cc4b80bd8d51eb765d7465881e694c7563"},"schema_version":"1.0"},"canonical_sha256":"1650d659fd7440ef12db9a0fd4f60974d698bf38be4ac02b45ca5e5818c67c8e","receipt":{"kind":"pith_receipt","key_id":"pith-v1-2026-05","algorithm":"ed25519","signed_at":"2026-05-18T00:52:44.419784Z","signature_b64":"DrXmQy1EeelLK6hOxVfHGqecAwC8oFpIQ28RXVQZbq85W4/lgo0HszWX9gGbttt0bKAgFb3RiGOxvLwu2F2lBw==","signed_message":"canonical_sha256_bytes","builder_version":"pith-number-builder-2026-05-17-v1","receipt_version":"0.3","canonical_sha256":"1650d659fd7440ef12db9a0fd4f60974d698bf38be4ac02b45ca5e5818c67c8e","last_reissued_at":"2026-05-18T00:52:44.419427Z","signature_status":"signed_v1","first_computed_at":"2026-05-18T00:52:44.419427Z","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"source_kind":"arxiv","source_id":"1510.04612","source_version":1,"attestation_state":"computed"},"signer":{"signer_id":"pith.science","signer_type":"pith_registry","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"created_at":"2026-05-18T00:52:44Z","supersedes":[],"prev_event":null,"signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"4WL4lh11YhGsoJaB/YRQERGQSpcUmirNHmsOapqMKvmZzziLS/gxz54vN732bjFPPEekSPTKWrZs2NNNRtdxBA==","signed_message":"open_graph_event_sha256_bytes","signed_at":"2026-05-30T15:04:33.657390Z"},"content_sha256":"ee8a29a930cb0fd24064ef248ca4bd0a8efd2875e6dcad48a54bcbe1e11270e9","schema_version":"1.0","event_id":"sha256:ee8a29a930cb0fd24064ef248ca4bd0a8efd2875e6dcad48a54bcbe1e11270e9"},{"event_type":"graph_snapshot","subject_pith_number":"pith:2015:CZINMWP5ORAO6EW3TIH5J5QJOT","target":"graph","payload":{"graph_snapshot":{"paper":{"title":"Quantification of the effect of mutations using a global probability model of natural sequence variation","license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","headline":"","cross_cats":[],"primary_cat":"q-bio.BM","authors_text":"Chris Sander, Debora S. Marks, Frank J. Poelwijk, John B. Ingraham, Michael Springer, Thomas A. Hopf","submitted_at":"2015-10-15T16:34:12Z","abstract_excerpt":"Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored. Fortunately, the mutation-selection process of natural evolution has recorded rich information in the diversity of natural protein sequences. Here, building on probabilistic models for correlated amino-acid substitutions that have been successfully applied to determine the three-dimensional structures of proteins, we present a statistical approach for quantifyin"},"claims":{"count":0,"items":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"source":{"id":"1510.04612","kind":"arxiv","version":1},"verdict":{"id":null,"model_set":{},"created_at":null,"strongest_claim":"","one_line_summary":"","pipeline_version":null,"weakest_assumption":"","pith_extraction_headline":""},"references":{"count":0,"sample":[],"resolved_work":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57","internal_anchors":0},"formal_canon":{"evidence_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"author_claims":{"count":0,"strong_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"builder_version":"pith-number-builder-2026-05-17-v1"},"verdict_id":null},"signer":{"signer_id":"pith.science","signer_type":"pith_registry","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"created_at":"2026-05-18T00:52:44Z","supersedes":[],"prev_event":null,"signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"VNmiUo5kd3wmRnpGvBwtaynjNcvJuGns8qiThczBoa4Txq8dg6xB6gZZhQ8AES9I5r/J3CTFVcFbXGsTcp2vCg==","signed_message":"open_graph_event_sha256_bytes","signed_at":"2026-05-30T15:04:33.657753Z"},"content_sha256":"08b6e8f35d2b9bed7ca10cc8597b481e53bd02207110a130171e768a4f6f106c","schema_version":"1.0","event_id":"sha256:08b6e8f35d2b9bed7ca10cc8597b481e53bd02207110a130171e768a4f6f106c"}],"timestamp_proofs":[],"mirror_hints":[{"mirror_type":"https","name":"Pith Resolver","base_url":"https://pith.science","bundle_url":"https://pith.science/pith/CZINMWP5ORAO6EW3TIH5J5QJOT/bundle.json","state_url":"https://pith.science/pith/CZINMWP5ORAO6EW3TIH5J5QJOT/state.json","well_known_bundle_url":"https://pith.science/.well-known/pith/CZINMWP5ORAO6EW3TIH5J5QJOT/bundle.json","status":"primary"}],"public_keys":[{"key_id":"pith-v1-2026-05","algorithm":"ed25519","format":"raw","public_key_b64":"stVStoiQhXFxp4s2pdzPNoqVNBMojDU/fJ2db5S3CbM=","public_key_hex":"b2d552b68890857171a78b36a5dccf368a953413288c353f7c9d9d6f94b709b3","fingerprint_sha256_b32_first128bits":"RVFV5Z2OI2J3ZUO7ERDEBCYNKS","fingerprint_sha256_hex":"8d4b5ee74e4693bcd1df2446408b0d54","rotates_at":null,"url":"https://pith.science/pith-signing-key.json","notes":"Pith uses this Ed25519 key to sign canonical record SHA-256 digests. Verify with: ed25519_verify(public_key, message=canonical_sha256_bytes, signature=base64decode(signature_b64))."}],"merge_version":"pith-open-graph-merge-v1","built_at":"2026-05-30T15:04:33Z","links":{"resolver":"https://pith.science/pith/CZINMWP5ORAO6EW3TIH5J5QJOT","bundle":"https://pith.science/pith/CZINMWP5ORAO6EW3TIH5J5QJOT/bundle.json","state":"https://pith.science/pith/CZINMWP5ORAO6EW3TIH5J5QJOT/state.json","well_known_bundle":"https://pith.science/.well-known/pith/CZINMWP5ORAO6EW3TIH5J5QJOT/bundle.json"},"state":{"state_type":"pith_open_graph_state","state_version":"1.0","pith_number":"pith:2015:CZINMWP5ORAO6EW3TIH5J5QJOT","merge_version":"pith-open-graph-merge-v1","event_count":2,"valid_event_count":2,"invalid_event_count":0,"equivocation_count":0,"current":{"canonical_record":{"metadata":{"abstract_canon_sha256":"f870f5cd1c04c1d5c8914a20aa8600cc4b80bd8d51eb765d7465881e694c7563","cross_cats_sorted":[],"license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","primary_cat":"q-bio.BM","submitted_at":"2015-10-15T16:34:12Z","title_canon_sha256":"cfda17aa79497d58ea57ab99367d49cb7d338e57258407350cb244d5c166a520"},"schema_version":"1.0","source":{"id":"1510.04612","kind":"arxiv","version":1}},"source_aliases":[{"alias_kind":"arxiv","alias_value":"1510.04612","created_at":"2026-05-18T00:52:44Z"},{"alias_kind":"arxiv_version","alias_value":"1510.04612v1","created_at":"2026-05-18T00:52:44Z"},{"alias_kind":"doi","alias_value":"10.48550/arxiv.1510.04612","created_at":"2026-05-18T00:52:44Z"},{"alias_kind":"pith_short_12","alias_value":"CZINMWP5ORAO","created_at":"2026-05-18T12:29:17Z"},{"alias_kind":"pith_short_16","alias_value":"CZINMWP5ORAO6EW3","created_at":"2026-05-18T12:29:17Z"},{"alias_kind":"pith_short_8","alias_value":"CZINMWP5","created_at":"2026-05-18T12:29:17Z"}],"graph_snapshots":[{"event_id":"sha256:08b6e8f35d2b9bed7ca10cc8597b481e53bd02207110a130171e768a4f6f106c","target":"graph","created_at":"2026-05-18T00:52:44Z","signer":{"key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signer_id":"pith.science","signer_type":"pith_registry"},"payload":{"graph_snapshot":{"author_claims":{"count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57","strong_count":0},"builder_version":"pith-number-builder-2026-05-17-v1","claims":{"count":0,"items":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"formal_canon":{"evidence_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"paper":{"abstract_excerpt":"Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored. Fortunately, the mutation-selection process of natural evolution has recorded rich information in the diversity of natural protein sequences. Here, building on probabilistic models for correlated amino-acid substitutions that have been successfully applied to determine the three-dimensional structures of proteins, we present a statistical approach for quantifyin","authors_text":"Chris Sander, Debora S. Marks, Frank J. Poelwijk, John B. Ingraham, Michael Springer, Thomas A. Hopf","cross_cats":[],"headline":"","license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","primary_cat":"q-bio.BM","submitted_at":"2015-10-15T16:34:12Z","title":"Quantification of the effect of mutations using a global probability model of natural sequence variation"},"references":{"count":0,"internal_anchors":0,"resolved_work":0,"sample":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"source":{"id":"1510.04612","kind":"arxiv","version":1},"verdict":{"created_at":null,"id":null,"model_set":{},"one_line_summary":"","pipeline_version":null,"pith_extraction_headline":"","strongest_claim":"","weakest_assumption":""}},"verdict_id":null}}],"author_attestations":[],"timestamp_anchors":[],"storage_attestations":[],"citation_signatures":[],"replication_records":[],"corrections":[],"mirror_hints":[],"record_created":{"event_id":"sha256:ee8a29a930cb0fd24064ef248ca4bd0a8efd2875e6dcad48a54bcbe1e11270e9","target":"record","created_at":"2026-05-18T00:52:44Z","signer":{"key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signer_id":"pith.science","signer_type":"pith_registry"},"payload":{"attestation_state":"computed","canonical_record":{"metadata":{"abstract_canon_sha256":"f870f5cd1c04c1d5c8914a20aa8600cc4b80bd8d51eb765d7465881e694c7563","cross_cats_sorted":[],"license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","primary_cat":"q-bio.BM","submitted_at":"2015-10-15T16:34:12Z","title_canon_sha256":"cfda17aa79497d58ea57ab99367d49cb7d338e57258407350cb244d5c166a520"},"schema_version":"1.0","source":{"id":"1510.04612","kind":"arxiv","version":1}},"canonical_sha256":"1650d659fd7440ef12db9a0fd4f60974d698bf38be4ac02b45ca5e5818c67c8e","receipt":{"algorithm":"ed25519","builder_version":"pith-number-builder-2026-05-17-v1","canonical_sha256":"1650d659fd7440ef12db9a0fd4f60974d698bf38be4ac02b45ca5e5818c67c8e","first_computed_at":"2026-05-18T00:52:44.419427Z","key_id":"pith-v1-2026-05","kind":"pith_receipt","last_reissued_at":"2026-05-18T00:52:44.419427Z","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","receipt_version":"0.3","signature_b64":"DrXmQy1EeelLK6hOxVfHGqecAwC8oFpIQ28RXVQZbq85W4/lgo0HszWX9gGbttt0bKAgFb3RiGOxvLwu2F2lBw==","signature_status":"signed_v1","signed_at":"2026-05-18T00:52:44.419784Z","signed_message":"canonical_sha256_bytes"},"source_id":"1510.04612","source_kind":"arxiv","source_version":1}}},"equivocations":[],"invalid_events":[],"applied_event_ids":["sha256:ee8a29a930cb0fd24064ef248ca4bd0a8efd2875e6dcad48a54bcbe1e11270e9","sha256:08b6e8f35d2b9bed7ca10cc8597b481e53bd02207110a130171e768a4f6f106c"],"state_sha256":"57c46f189a3f7d650580258ea2d06bf3f72531874dc5c1f2c2c840f0ca9cf2b4"},"bundle_signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"0B2RQ8yFi8LcZWd5snwDtB5T4PTHxo4YjRNjxYS7NepAsuvV87LV714EJcmGzbdNgDDIeCW2uu4WPr9IIrl6DA==","signed_message":"bundle_sha256_bytes","signed_at":"2026-05-30T15:04:33.660013Z","bundle_sha256":"9b361c99ed926de6bf0f605b1fa3fe6ef0da01b13d22fdf1cf88ba1e3216ecc7"}}